diff --git "a/data/ppi_llm/ppi_l3_dataset.jsonl" "b/data/ppi_llm/ppi_l3_dataset.jsonl" new file mode 100644--- /dev/null +++ "b/data/ppi_llm/ppi_l3_dataset.jsonl" @@ -0,0 +1,200 @@ +{"question_id": "PPIL3-0000", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: MSH6 (P52701, 1360 AA)\n Function: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction\n Location: Nucleus\n Domains: PWWP\n\nProtein 2: FYTTD1 (Q96QD9, 318 AA)\n Function: Required for mRNA export from the nucleus to the cytoplasm. Acts as an adapter that uses the DDX39B/UAP56-NFX1 pathway to ensure efficient mRNA export and delivering to the nuclear pore. Associates with spliced and unspliced mRNAs simultaneously with ALYREF/THOC4\n Location: Nucleus, nucleoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 838835, "gene_symbol_1": "MSH6", "gene_symbol_2": "FYTTD1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P52701", "uniprot_2": "Q96QD9"}, "gold_reasoning": "MSH6 is described as: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha be. FYTTD1 is described as: Required for mRNA export from the nucleus to the cytoplasm. Acts as an adapter that uses the DDX39B/UAP56-NFX1 pathway to ensure efficient mRNA export and delivering to the nuclear pore. Associates wi. These distinct biological roles suggest limited functional overlap requiring direct physical association. MSH6 localizes to Nucleus, while FYTTD1 localizes to Nucleus, nucleoplasm. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between MSH6 and FYTTD1."} +{"question_id": "PPIL3-0001", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: RXRB (P28702, 533 AA)\n Function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE)\n Location: Nucleus\n Domains: NR LBD\n\nProtein 2: GEMIN7 (Q9H840, 131 AA)\n Function: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP\n Location: Nucleus, nucleoplasm\n Domains: SUZ-C; Sm\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1530099, "gene_symbol_1": "RXRB", "gene_symbol_2": "GEMIN7", "detection_method": null, "compartment_type": "same", "uniprot_1": "P28702", "uniprot_2": "Q9H840"}, "gold_reasoning": "RXRB is described as: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression . GEMIN7 is described as: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. . These distinct biological roles suggest limited functional overlap requiring direct physical association. RXRB localizes to Nucleus, while GEMIN7 localizes to Nucleus, nucleoplasm. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between RXRB and GEMIN7."} +{"question_id": "PPIL3-0002", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: TMEM30A (Q9NV96, 361 AA)\n Function: Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF), synthetic drug alkylphospholipid edelfosine, and, probably in association with ATP8B1, of perifosine. Also mediates the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations\n Location: Membrane\n Domains: None\n\nProtein 2: LAMA2 (P24043, 3122 AA)\n Function: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components\n Location: Secreted, extracellular space, extracellular matrix, basement membrane\n Domains: Laminin EGF-like 1; Laminin EGF-like 10; Laminin EGF-like 11; Laminin EGF-like 12; Laminin EGF-like 13; Laminin EGF-like 14; first part; Laminin EGF-like 14; second part; Laminin EGF-like 15; Laminin EGF-like 16; Laminin EGF-like 17; Laminin EGF-like 2; Laminin EGF-like 3; Laminin EGF-like 4; Laminin EGF-like 5; first part; Laminin EGF-like 5; second part; Laminin EGF-like 6; Laminin EGF-like 7; Laminin EGF-like 8; Laminin EGF-like 9; Laminin G-like 1; Laminin G-like 2; Laminin G-like 3; Laminin G-like 4; Laminin G-like 5; Laminin IV type A 1; Laminin IV type A 2; Laminin N-terminal\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1720935, "gene_symbol_1": "TMEM30A", "gene_symbol_2": "LAMA2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9NV96", "uniprot_2": "P24043"}, "gold_reasoning": "TMEM30A is described as: Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en. LAMA2 is described as: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext. These distinct biological roles suggest limited functional overlap requiring direct physical association. TMEM30A localizes to Membrane, while LAMA2 localizes to Secreted, extracellular space, extracellular matrix, basement membrane. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between TMEM30A and LAMA2."} +{"question_id": "PPIL3-0003", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: VTN (P04004, 478 AA)\n Function: Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway\n Location: Secreted, extracellular space\n Domains: SMB\n\nProtein 2: ATP5PD (O75947, 161 AA)\n Function: Subunit d, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). Part of the complex F(0) domain (PubMed:37244256). Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements (By similarity)\n Location: Mitochondrion\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 665669, "gene_symbol_1": "VTN", "gene_symbol_2": "ATP5PD", "detection_method": null, "compartment_type": "different", "uniprot_1": "P04004", "uniprot_2": "O75947"}, "gold_reasoning": "VTN is described as: Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family . ATP5PD is described as: Subunit d, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generate. These distinct biological roles suggest limited functional overlap requiring direct physical association. VTN localizes to Secreted, extracellular space, while ATP5PD localizes to Mitochondrion. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between VTN and ATP5PD."} +{"question_id": "PPIL3-0004", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: ITGB2 (P05107, 769 AA)\n Function: Integrin ITGAL:ITGB2 is a receptor for ICAM1, ICAM2 and ICAM3 (PubMed:1676048, PubMed:23775590, PubMed:38195629). Integrin ITGAL:ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL (PubMed:29100055). Integrins ITGAM:ITGB2 and ITGAX:ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX:ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM:ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM:ITGB2 is also a receptor for factor X. Integrin ITGAD:ITGB2 is a receptor for ICAM3 and VCAM1 (PubMed:10438935, PubMed:8777714, PubMed:9841932). Contributes to natural killer cell cytotoxicity (PubMed:15356110). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:11812992, PubMed:28807980). Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation (PubMed:18587400). Integrin ITGAL:ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). Integrins ITGAX:ITGB2 functions as a receptor of the erythrocyte-specific adhesion molecule ICAM4 and mediates erythrophagocytosis (PubMed:16985175). Integrins ITGAX:ITGB2 functions as a receptor of the neuron-specific adhesion molecule ICAM5 ensuring neuron cell-leukocyte adhesion (PubMed:10741396). Integrin ITGAL:ITGB2 functions as a receptor of ICAM1 by acting as a platform at the immunological synapse to translate TCR engagement and density of the ITGAL ligand ICAM1 into graded adhesion (PubMed:38195629). Integrin ITGAM:ITGB2/MAC-1 complex functions as a signaling receptor for the ligand receptor ICAM1, ensuring adhesion between stimulated neutrophils and stimulated endothelial cells (PubMed:1980124). Integrin ITGAL/ITGB2 that functions as a signaling receptor of ICAM2, ensuring leukocyte cell-cell adhesion on resting cells (PubMed:1676048)\n Location: Cell membrane\n Domains: I-EGF 1; I-EGF 2; I-EGF 3; I-EGF 4; PSI; VWFA\n\nProtein 2: XRCC5 (P13010, 732 AA)\n Function: DNA-binding protein critical for the DNA damage response, specifically in repairing double-strand breaks (DSBs) via the classical non-homologous end joining (NHEJ) pathway. It forms a heterodimer with XRCC6 (Ku70), creating the Ku70:Ku80 heterodimer (Ku complex), which serves as a DNA end-binding complex. It primarily binds DSBs and recruits essential repair factors, assembling the core long-range NHEJ complex to facilitate the alignment and ligation of broken DNA ends (PubMed:11493912, PubMed:33854234, PubMed:34352203). This pathway ensures the rapid repair of cytotoxic and mutagenic DSBs and contributes to the generation of diversity in T-cell receptors and antibodies through mechanisms such as V(D)J recombination (PubMed:9742108). Likely acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), catalyzing the beta-elimination of the 5'-deoxyribose-5-phosphate at abasic sites near DSBs. This activity cleans the termini of abasic sites, a common form of nucleotide damage, preparing broken ends for ligation (PubMed:20383123). It may also possess 3'-5' DNA helicase activity, although this has not been confirmed in vivo, and its physiological significance remains unclear (PubMed:7957065). Beyond DNA repair, the protein contributes to telomere maintenance (PubMed:29490055). It is also implicated in transcriptional regulation, acting as a cofactor for various transcription factors (PubMed:12145306, PubMed:8621488). It plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Can also bind RNAs and recruits PRKDC to a wide range of cellular RNAs, including the U3 small nucleolar RNA, playing a role in the biogenesis of ribosomal RNAs (PubMed:32103174)\n Location: Nucleus\n Domains: Ku; VWFA\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1523223, "gene_symbol_1": "ITGB2", "gene_symbol_2": "XRCC5", "detection_method": null, "compartment_type": "different", "uniprot_1": "P05107", "uniprot_2": "P13010"}, "gold_reasoning": "ITGB2 is described as: Integrin ITGAL:ITGB2 is a receptor for ICAM1, ICAM2 and ICAM3 (PubMed:1676048, PubMed:23775590, PubMed:38195629). Integrin ITGAL:ITGB2 is also a receptor for the secreted form of ubiquitin-like protei. XRCC5 is described as: DNA-binding protein critical for the DNA damage response, specifically in repairing double-strand breaks (DSBs) via the classical non-homologous end joining (NHEJ) pathway. It forms a heterodimer with. These distinct biological roles suggest limited functional overlap requiring direct physical association. ITGB2 localizes to Cell membrane, while XRCC5 localizes to Nucleus. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between ITGB2 and XRCC5."} +{"question_id": "PPIL3-0005", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: CNOT7 (Q9UIV1, 285 AA)\n Function: Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (PubMed:19605561). Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation (PubMed:19276069, PubMed:20634287, PubMed:31439799). During miRNA-mediated repression the complex also seems to act as translational repressor during translational initiation (PubMed:20065043). Additional complex functions may be a consequence of its influence on mRNA expression (PubMed:19276069, PubMed:23236473). Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity (PubMed:19276069, PubMed:23236473)\n Location: Nucleus\n Domains: None\n\nProtein 2: CASTOR2 (A6NHX0, 329 AA)\n Function: Functions as a negative regulator of the TORC1 signaling pathway through the GATOR complex. As part of homodimers or heterodimers with CASTOR1, directly binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1. Does not directly bind arginine, but binding of arginine to CASTOR1 disrupts the interaction of CASTOR2-containing heterodimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway\n Location: Cytoplasm, cytosol\n Domains: ACT 1; ACT 2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1241197, "gene_symbol_1": "CNOT7", "gene_symbol_2": "CASTOR2", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9UIV1", "uniprot_2": "A6NHX0"}, "gold_reasoning": "CNOT7 is described as: Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub. CASTOR2 is described as: Functions as a negative regulator of the TORC1 signaling pathway through the GATOR complex. As part of homodimers or heterodimers with CASTOR1, directly binds and inhibits the GATOR subcomplex GATOR2 . These distinct biological roles suggest limited functional overlap requiring direct physical association. CNOT7 localizes to Nucleus, while CASTOR2 localizes to Cytoplasm, cytosol. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between CNOT7 and CASTOR2."} +{"question_id": "PPIL3-0006", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: GALNT8 (Q9NY28, 637 AA)\n Function: Probably catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor\n Location: Golgi apparatus membrane\n Domains: Ricin B-type lectin\n\nProtein 2: EMC9 (Q9Y3B6, 208 AA)\n Function: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:29242231, PubMed:29809151, PubMed:30415835, PubMed:32459176). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:29242231, PubMed:29809151, PubMed:30415835). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:29809151, PubMed:30415835). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29242231, PubMed:29809151). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable)\n Location: Endoplasmic reticulum membrane\n Domains: MPN\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 495848, "gene_symbol_1": "GALNT8", "gene_symbol_2": "EMC9", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9NY28", "uniprot_2": "Q9Y3B6"}, "gold_reasoning": "GALNT8 is described as: Probably catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. EMC9 is described as: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:29242. These distinct biological roles suggest limited functional overlap requiring direct physical association. GALNT8 localizes to Golgi apparatus membrane, while EMC9 localizes to Endoplasmic reticulum membrane. Different subcellular compartments reduce the probability of direct interaction. Systematic yeast two-hybrid screening tested this pair across multiple replicates and found no positive interaction signal."} +{"question_id": "PPIL3-0007", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: CYBB (P04839, 570 AA)\n Function: Catalytic subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:15338276, PubMed:36241643, PubMed:36413210, PubMed:38355798). In the activated complex, electrons are first transferred from NADPH to flavin adenine dinucleotide (FAD) and subsequently transferred via two heme molecules to molecular oxygen, producing superoxide through an outer-sphere reaction (Probable) (PubMed:38355798). Activation of the NADPH oxidase complex is initiated by the assembly of cytosolic subunits of the NADPH oxidase complex with the core NADPH oxidase complex to form a complex at the plasma membrane or phagosomal membrane (PubMed:19028840, PubMed:38355798). This activation process is initiated by phosphorylation dependent binding of the cytosolic NCF1/p47-phox subunit to the C-terminus of CYBA/p22-phox (By similarity). NADPH oxidase complex assembly is impaired through interaction with NRROS (By similarity)\n Location: Cell membrane\n Domains: FAD-binding FR-type; Ferric oxidoreductase\n\nProtein 2: TERF1 (P54274, 439 AA)\n Function: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length (PubMed:31595153). Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways\n Location: Nucleus\n Domains: HTH myb-type\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 712634, "gene_symbol_1": "CYBB", "gene_symbol_2": "TERF1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P04839", "uniprot_2": "P54274"}, "gold_reasoning": "CYBB is described as: Catalytic subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:15338276, PubMed:36241643, P. TERF1 is described as: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length (PubMed:31595153). Involved in the regulation of the mitotic spindle. Component of the shelterin comple. These distinct biological roles suggest limited functional overlap requiring direct physical association. CYBB localizes to Cell membrane, while TERF1 localizes to Nucleus. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between CYBB and TERF1."} +{"question_id": "PPIL3-0008", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: STOX1 (Q6ZVD7, 989 AA)\n Function: Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta (PubMed:24738702). Required for regulation of inner ear epithelial cell proliferation via the AKT signaling pathway (By similarity)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: RTRAF (Q9Y224, 244 AA)\n Function: Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester (PubMed:21311021, PubMed:24870230). RNA-binding protein involved in modulation of mRNA transcription by Polymerase II (PubMed:16950395). Could also play a role in RNA transport (PubMed:24608264)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 382474, "gene_symbol_1": "STOX1", "gene_symbol_2": "RTRAF", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q6ZVD7", "uniprot_2": "Q9Y224"}, "gold_reasoning": "STOX1 is described as: Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta (PubMed:24738702). Required for regulation of inner ear e. RTRAF is described as: Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the . These distinct biological roles suggest limited functional overlap requiring direct physical association. STOX1 localizes to Cytoplasm, while RTRAF localizes to Nucleus. Different subcellular compartments reduce the probability of direct interaction. Systematic yeast two-hybrid screening tested this pair across multiple replicates and found no positive interaction signal."} +{"question_id": "PPIL3-0009", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: ABCB8 (Q9NUT2, 735 AA)\n Function: ATP-binding subunit of the mitochondrial ATP-gated potassium channel (mitoK(ATP)) (PubMed:31435016). Together with pore-forming subunit CCDC51/MITOK of the mitoK(ATP) channel, mediates ATP-dependent potassium currents across the mitochondrial inner membrane (PubMed:31435016). An increase in ATP intracellular levels closes the channel, inhibiting K(+) transport, whereas a decrease in ATP levels enhances K(+) uptake in the mitochondrial matrix (PubMed:31435016). Plays a role in mitochondrial iron transport (PubMed:30623799). Required for maintenance of normal cardiac function, possibly by influencing mitochondrial iron export and regulating the maturation of cytosolic iron sulfur cluster-containing enzymes (By similarity)\n Location: Mitochondrion inner membrane\n Domains: ABC transmembrane type-1; ABC transporter\n\nProtein 2: TLR10 (Q9BXR5, 811 AA)\n Function: Participates in the innate immune response to microbial agents. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity)\n Location: Membrane\n Domains: LRRCT; TIR\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 581026, "gene_symbol_1": "ABCB8", "gene_symbol_2": "TLR10", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9NUT2", "uniprot_2": "Q9BXR5"}, "gold_reasoning": "ABCB8 is described as: ATP-binding subunit of the mitochondrial ATP-gated potassium channel (mitoK(ATP)) (PubMed:31435016). Together with pore-forming subunit CCDC51/MITOK of the mitoK(ATP) channel, mediates ATP-dependent p. TLR10 is described as: Participates in the innate immune response to microbial agents. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity). These distinct biological roles suggest limited functional overlap requiring direct physical association. ABCB8 localizes to Mitochondrion inner membrane, while TLR10 localizes to Membrane. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between ABCB8 and TLR10."} +{"question_id": "PPIL3-0010", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: GABRA2 (P47869, 451 AA)\n Function: Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:10449790, PubMed:29961870, PubMed:31032849). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:10449790). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). The alpha-2 subunit exhibits synaptogenic activity together with beta-2 and very little to no activity together with beta-3, the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (By similarity)\n Location: Postsynaptic cell membrane\n Domains: None\n\nProtein 2: MCU (Q8NE86, 351 AA)\n Function: Channel-forming and calcium-conducting subunit of the mitochondrial inner membrane calcium uniporter complex (uniplex), which mediates calcium uptake into the mitochondrial matrix (PubMed:21685886, PubMed:21685888, PubMed:22822213, PubMed:22829870, PubMed:22904319, PubMed:23101630, PubMed:23178883, PubMed:23755363, PubMed:24332854, PubMed:24560927, PubMed:26341627, PubMed:29954988, PubMed:29995857, PubMed:30454562, PubMed:30638448, PubMed:31080062, PubMed:32494073, PubMed:32762847, PubMed:33296646, PubMed:37036971, PubMed:37126688). MCU channel activity is regulated by the calcium-sensor subunits of the uniplex MICU1 and MICU2 (or MICU3) (PubMed:24560927, PubMed:26903221, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32762847, PubMed:37036971, PubMed:37126688). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates ATP production, cytoplasmic calcium signals and activation of cell death pathways (PubMed:21685886, PubMed:21685888, PubMed:22822213, PubMed:22829870, PubMed:22904319, PubMed:23101630, PubMed:23178883, PubMed:23755363, PubMed:24332854, PubMed:24560927, PubMed:26341627, PubMed:29954988, PubMed:32494073, PubMed:32762847). Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (PubMed:22822213). While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells (PubMed:25603276). Participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22829870, PubMed:22904319). Involved in antigen processing and presentation (By similarity)\n Location: Mitochondrion inner membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 723516, "gene_symbol_1": "GABRA2", "gene_symbol_2": "MCU", "detection_method": null, "compartment_type": "same", "uniprot_1": "P47869", "uniprot_2": "Q8NE86"}, "gold_reasoning": "GABRA2 is described as: Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:10449790, PubMed:29961870, PubMed:. MCU is described as: Channel-forming and calcium-conducting subunit of the mitochondrial inner membrane calcium uniporter complex (uniplex), which mediates calcium uptake into the mitochondrial matrix (PubMed:21685886, Pu. These distinct biological roles suggest limited functional overlap requiring direct physical association. GABRA2 localizes to Postsynaptic cell membrane, while MCU localizes to Mitochondrion inner membrane. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between GABRA2 and MCU."} +{"question_id": "PPIL3-0011", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: MED11 (Q9P086, 117 AA)\n Function: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors\n Location: Nucleus\n Domains: None\n\nProtein 2: ETFB (P38117, 255 AA)\n Function: Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:15159392, PubMed:15975918, PubMed:25416781). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMP molecule that probably has a purely structural role (PubMed:15159392, PubMed:15975918, PubMed:8962055)\n Location: Mitochondrion matrix\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 613046, "gene_symbol_1": "MED11", "gene_symbol_2": "ETFB", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9P086", "uniprot_2": "P38117"}, "gold_reasoning": "MED11 is described as: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene. ETFB is described as: Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:15159. These distinct biological roles suggest limited functional overlap requiring direct physical association. MED11 localizes to Nucleus, while ETFB localizes to Mitochondrion matrix. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between MED11 and ETFB."} +{"question_id": "PPIL3-0012", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: NPRL3 (Q12980, 569 AA)\n Function: As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, PubMed:35338845). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (PubMed:23723238, PubMed:29590090, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway (PubMed:23723238)\n Location: Lysosome membrane\n Domains: None\n\nProtein 2: WTAP (Q15007, 396 AA)\n Function: Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Required for accumulation of METTL3 and METTL14 to nuclear speckle (PubMed:24316715, PubMed:24407421, PubMed:24981863). Acts as a mRNA splicing regulator (PubMed:12444081). Regulates G2/M cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances its stability (PubMed:17088532). Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes (PubMed:17095724)\n Location: Nucleus speckle\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 667086, "gene_symbol_1": "NPRL3", "gene_symbol_2": "WTAP", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q12980", "uniprot_2": "Q15007"}, "gold_reasoning": "NPRL3 is described as: As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, PubMed:35338845). In response to amino acid dep. WTAP is described as: Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (P. These distinct biological roles suggest limited functional overlap requiring direct physical association. NPRL3 localizes to Lysosome membrane, while WTAP localizes to Nucleus speckle. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between NPRL3 and WTAP."} +{"question_id": "PPIL3-0013", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: MCM6 (Q14566, 821 AA)\n Function: Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425)\n Location: Nucleus\n Domains: MCM C-terminal AAA(+) ATPase\n\nProtein 2: CEBPA (P49715, 358 AA)\n Function: Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes (PubMed:11242107). During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (By similarity). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Down-regulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters. Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1225524, "gene_symbol_1": "MCM6", "gene_symbol_2": "CEBPA", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q14566", "uniprot_2": "P49715"}, "gold_reasoning": "MCM6 is described as: Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core compon. CEBPA is described as: Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consen. These distinct biological roles suggest limited functional overlap requiring direct physical association. Although both proteins are found in Nucleus, co-localization alone does not imply physical interaction. Experimental evidence does not support a physical interaction between MCM6 and CEBPA."} +{"question_id": "PPIL3-0014", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: SMC1B (Q8NDV3, 1235 AA)\n Function: Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation and the organization of chromatin loops along the AE. Plays a key role in synapsis, recombination and chromosome movements. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I (By similarity)\n Location: Nucleus\n Domains: SMC hinge\n\nProtein 2: SLBP (Q14493, 270 AA)\n Function: RNA-binding protein involved in the histone pre-mRNA processing (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Binds the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilizing the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Stabilizes mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Involved in the mechanism by which growing oocytes accumulate histone proteins that support early embryogenesis (By similarity). Binds to the 5' side of the stem-loop structure of histone pre-mRNAs (By similarity)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1139678, "gene_symbol_1": "SMC1B", "gene_symbol_2": "SLBP", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q8NDV3", "uniprot_2": "Q14493"}, "gold_reasoning": "SMC1B is described as: Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation . SLBP is described as: RNA-binding protein involved in the histone pre-mRNA processing (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Binds the stem-loop structure of replication-dependent histone pre-m. These distinct biological roles suggest limited functional overlap requiring direct physical association. SMC1B localizes to Nucleus, while SLBP localizes to Cytoplasm. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between SMC1B and SLBP."} +{"question_id": "PPIL3-0015", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: MMS19 (Q96T76, 1030 AA)\n Function: Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity (PubMed:29848660). In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in nucleotide excision repair (NER), homologous recombination-mediated double-strand break DNA repair, DNA replication and RNA polymerase II (POL II) transcription (PubMed:22678361, PubMed:22678362, PubMed:23585563, PubMed:29225034). As part of the mitotic spindle-associated MMXD complex, plays a role in chromosome segregation, probably by facilitating iron-sulfur (Fe-S) cluster assembly into ERCC2/XPD (PubMed:20797633). Together with CIAO2, facilitates the transfer of Fe-S clusters to the motor protein KIF4A, which ensures proper localization of KIF4A to mitotic machinery components to promote the progression of mitosis (PubMed:29848660). Indirectly acts as a transcriptional coactivator of estrogen receptor (ER), via its role in iron-sulfur insertion into some component of the TFIIH-machinery (PubMed:11279242)\n Location: Nucleus\n Domains: None\n\nProtein 2: MATN1 (P21941, 496 AA)\n Function: A major component of the extracellular matrix of non-articular cartilage (By similarity). Binds to type 2 collagens and forms long concatenated protein networks as part of the extracellular matrix (By similarity). Required for the network-like organization and bundling of collagen fibrils surrounding chondrocytes in the zones of maturation and hypertrophy (By similarity). Required for mechanotransduction and adaption to mechanical loading in cartilage chondrocytes, resulting in an increase in expression of the extracellular matrix components ACAN and COL2A1 (By similarity). Acts as a moderator of angiogenesis in response to injury (By similarity)\n Location: Secreted, extracellular space, extracellular matrix\n Domains: EGF-like; VWFA 1; VWFA 2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1442556, "gene_symbol_1": "MMS19", "gene_symbol_2": "MATN1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q96T76", "uniprot_2": "P21941"}, "gold_reasoning": "MMS19 is described as: Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA m. MATN1 is described as: A major component of the extracellular matrix of non-articular cartilage (By similarity). Binds to type 2 collagens and forms long concatenated protein networks as part of the extracellular matrix (By. These distinct biological roles suggest limited functional overlap requiring direct physical association. MMS19 localizes to Nucleus, while MATN1 localizes to Secreted, extracellular space, extracellular matrix. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between MMS19 and MATN1."} +{"question_id": "PPIL3-0016", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: DNAJC15 (Q9Y5T4, 150 AA)\n Function: Negative regulator of the mitochondrial respiratory chain. Prevents mitochondrial hyperpolarization state and restricts mitochondrial generation of ATP (By similarity). Acts as an import component of the TIM23 translocase complex. Stimulates the ATPase activity of HSPA9\n Location: Mitochondrion inner membrane\n Domains: J\n\nProtein 2: LAMA3 (Q16787, 3333 AA)\n Function: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components\n Location: Secreted, extracellular space, extracellular matrix, basement membrane\n Domains: Laminin EGF-like 1; Laminin EGF-like 10; Laminin EGF-like 11; Laminin EGF-like 12; Laminin EGF-like 13; Laminin EGF-like 14; Laminin EGF-like 15; truncated; Laminin EGF-like 2; Laminin EGF-like 3; Laminin EGF-like 4; Laminin EGF-like 5; Laminin EGF-like 6; Laminin EGF-like 7; Laminin EGF-like 8; Laminin EGF-like 9; Laminin G-like 1; Laminin G-like 2; Laminin G-like 3; Laminin G-like 4; Laminin G-like 5; Laminin IV type A; Laminin N-terminal\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1693231, "gene_symbol_1": "DNAJC15", "gene_symbol_2": "LAMA3", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9Y5T4", "uniprot_2": "Q16787"}, "gold_reasoning": "DNAJC15 is described as: Negative regulator of the mitochondrial respiratory chain. Prevents mitochondrial hyperpolarization state and restricts mitochondrial generation of ATP (By similarity). Acts as an import component of . LAMA3 is described as: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext. These distinct biological roles suggest limited functional overlap requiring direct physical association. DNAJC15 localizes to Mitochondrion inner membrane, while LAMA3 localizes to Secreted, extracellular space, extracellular matrix, basement membrane. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between DNAJC15 and LAMA3."} +{"question_id": "PPIL3-0017", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: SUV39H1 (O43463, 412 AA)\n Function: Histone methyltransferase that specifically mediates trimethylation of 'Lys-9' of histone H3 (H3K9me3) using monomethylated H3 'Lys-9' (H3K9me1) as substrate (PubMed:10949293, PubMed:11242053, PubMed:18004385, PubMed:40440427). Also weakly methylates histone H1 (in vitro) (PubMed:10949293). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones (PubMed:10949293, PubMed:11242053, PubMed:18004385). Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions (By similarity). H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats (By similarity). SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length (PubMed:11484059, PubMed:14765126, PubMed:16449642, PubMed:16818776, PubMed:16858404, PubMed:30111536). Involved in the maintenance of H3K9me3 mark following DNA replication, when histone marks are diluted: HP1 recognizes the preexisting H3K9me3 mark and serves as a platform to recruit SUV39H1 to modify the adjacent newly incorporated histones (PubMed:10949293, PubMed:11242053, PubMed:40440427). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes (PubMed:18485871). The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus (PubMed:18485871). Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation (By similarity)\n Location: Nucleus\n Domains: Chromo; Post-SET; Pre-SET; SET\n\nProtein 2: TGFB2 (P61812, 414 AA)\n Function: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively\n Location: Secreted, extracellular space, extracellular matrix\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 702013, "gene_symbol_1": "SUV39H1", "gene_symbol_2": "TGFB2", "detection_method": null, "compartment_type": "different", "uniprot_1": "O43463", "uniprot_2": "P61812"}, "gold_reasoning": "SUV39H1 is described as: Histone methyltransferase that specifically mediates trimethylation of 'Lys-9' of histone H3 (H3K9me3) using monomethylated H3 'Lys-9' (H3K9me1) as substrate (PubMed:10949293, PubMed:11242053, PubMed:. TGFB2 is described as: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively. These distinct biological roles suggest limited functional overlap requiring direct physical association. SUV39H1 localizes to Nucleus, while TGFB2 localizes to Secreted, extracellular space, extracellular matrix. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between SUV39H1 and TGFB2."} +{"question_id": "PPIL3-0018", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: ORC4 (O43929, 436 AA)\n Function: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3\n Location: Nucleus\n Domains: None\n\nProtein 2: CDCA8 (Q53HL2, 280 AA)\n Function: Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment\n Location: Nucleus, nucleolus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 649584, "gene_symbol_1": "ORC4", "gene_symbol_2": "CDCA8", "detection_method": null, "compartment_type": "same", "uniprot_1": "O43929", "uniprot_2": "Q53HL2"}, "gold_reasoning": "ORC4 is described as: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identifie. CDCA8 is described as: Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignm. These distinct biological roles suggest limited functional overlap requiring direct physical association. ORC4 localizes to Nucleus, while CDCA8 localizes to Nucleus, nucleolus. Different subcellular compartments reduce the probability of direct interaction. Experimental evidence does not support a physical interaction between ORC4 and CDCA8."} +{"question_id": "PPIL3-0019", "task": "ppi-l3", "split": "fewshot", "difficulty": "medium", "context_text": "Protein 1: CCT6A (P40227, 531 AA)\n Function: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: MLPH (Q9BV36, 600 AA)\n Function: Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A\n Location: Cytoplasm\n Domains: RabBD\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 211837, "gene_symbol_1": "CCT6A", "gene_symbol_2": "MLPH", "detection_method": null, "compartment_type": "same", "uniprot_1": "P40227", "uniprot_2": "Q9BV36"}, "gold_reasoning": "CCT6A is described as: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:364937. MLPH is described as: Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. These distinct biological roles suggest limited functional overlap requiring direct physical association. Although both proteins are found in Cytoplasm, co-localization alone does not imply physical interaction. Systematic yeast two-hybrid screening tested this pair across multiple replicates and found no positive interaction signal."} +{"question_id": "PPIL3-0020", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: TSHZ3 (Q63HK5, 1081 AA)\n Function: Transcriptional regulator involved in developmental processes. Functions in association with APBB1, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. TSHZ3-mediated transcription repression involves the recruitment of histone deacetylases HDAC1 and HDAC2. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s) (PubMed:19343227). Regulates the development of neurons involved in both respiratory rhythm and airflow control. Promotes maintenance of nucleus ambiguus (nA) motoneurons, which govern upper airway function, and establishes a respiratory rhythm generator (RRG) activity compatible with survival at birth. Involved in the differentiation of the proximal uretic smooth muscle cells during developmental processes. Involved in the up-regulation of myocardin, that directs the expression of smooth muscle cells in the proximal ureter (By similarity). Involved in the modulation of glutamatergic synaptic transmission and long-term synaptic potentiation (By similarity)\n Location: Nucleus\n Domains: None\n\nProtein 2: FRMD8 (Q9BZ67, 464 AA)\n Function: Promotes the cell surface stability of iRhom1/RHBDF1 and iRhom2/RHBDF2 and prevents their degradation via the endolysosomal pathway. By acting on iRhoms, involved in ADAM17-mediated shedding of TNF, amphiregulin/AREG, HBEGF and TGFA from the cell surface (PubMed:29897333, PubMed:29897336). Negatively regulates Wnt signaling, possibly by antagonizing the recruitment of AXIN1 to LRP6 (PubMed:19572019)\n Location: Cytoplasm, cytosol\n Domains: FERM\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 358184, "gene_symbol_1": "TSHZ3", "gene_symbol_2": "FRMD8", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q63HK5", "uniprot_2": "Q9BZ67"}} +{"question_id": "PPIL3-0021", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: ARHGAP1 (Q07960, 439 AA)\n Function: GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate\n Location: Cytoplasm\n Domains: CRAL-TRIO; Rho-GAP\n\nProtein 2: SBF2 (Q86WG5, 1849 AA)\n Function: Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28 (PubMed:20937701, PubMed:25648148). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (PubMed:20937701, PubMed:25648148). In response to starvation-induced autophagy, activates RAB21 which in turn binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (PubMed:25648148). Acts as an adapter for the phosphatase MTMR2 (By similarity). Increases MTMR2 catalytic activity towards phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards phosphatidylinositol 3-phosphate (By similarity)\n Location: Cytoplasm\n Domains: GRAM; Myotubularin phosphatase; PH; cDENN; dDENN; uDENN\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 283450, "gene_symbol_1": "ARHGAP1", "gene_symbol_2": "SBF2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q07960", "uniprot_2": "Q86WG5"}} +{"question_id": "PPIL3-0022", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: CDK11B (P21127, 795 AA)\n Function: Cyclin-dependent protein kinase that acts as a regulator of transcription and pre-mRNA splicing (PubMed:12501247, PubMed:18216018, PubMed:32367068, PubMed:36104565). Acts as a key regulator of pre-mRNA splicing by mediating phosphorylation of SF3B1, enabling the association between SF3B1 and U5 and U6 snRNAs in the activated spliceosome, thereby promoting spliceosome assembly (PubMed:36104565, PubMed:38059508). Also acts as a regulator of transcription by phosphorylating 'Ser-2' of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:32367068, PubMed:40858114). Involved in replication-dependent transcription of histone genes: binds to histone genes and phosphorylates POLR2A at 'Ser-2' of the CTD to specifically control transcriptional elongation of histones and recruitment of 3'-end processing factors (PubMed:32367068). Part of a transcription checkpoint upstream of CDK9, which regulates promoter-proximal pausing by RNA polymerase II, a transcription halt following transcription initiation, but prior to elongation (PubMed:40858114). Probably regulates promoter-proximal pausing by mediating phosphorylation of POLR2A at 'Ser-2' of the CTD (PubMed:40858114)\n Location: Nucleus\n Domains: Protein kinase\n\nProtein 2: VPS53 (Q5VIR6, 832 AA)\n Function: Acts as a component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (PubMed:15878329, PubMed:18367545). Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061)\n Location: Golgi apparatus, trans-Golgi network membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1579083, "gene_symbol_1": "CDK11B", "gene_symbol_2": "VPS53", "detection_method": null, "compartment_type": "different", "uniprot_1": "P21127", "uniprot_2": "Q5VIR6"}} +{"question_id": "PPIL3-0023", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: MED18 (Q9BUE0, 208 AA)\n Function: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors\n Location: Nucleus\n Domains: None\n\nProtein 2: BOP1 (Q14137, 746 AA)\n Function: Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome\n Location: Nucleus, nucleolus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 576280, "gene_symbol_1": "MED18", "gene_symbol_2": "BOP1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9BUE0", "uniprot_2": "Q14137"}} +{"question_id": "PPIL3-0024", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: MBP (P02686, 304 AA)\n Function: The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation\n Location: Myelin membrane\n Domains: None\n\nProtein 2: NIPAL4 (Q0D2K0, 404 AA)\n Function: Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Ba(2+), Sr(2+) and Fe(2+) but to a much less extent than Mg(2+) (By similarity). May be a receptor for ligands (trioxilins A3 and B3) from the hepoxilin pathway (PubMed:15317751)\n Location: Cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 125103, "gene_symbol_1": "MBP", "gene_symbol_2": "NIPAL4", "detection_method": null, "compartment_type": "same", "uniprot_1": "P02686", "uniprot_2": "Q0D2K0"}} +{"question_id": "PPIL3-0025", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: FADD (Q13158, 208 AA)\n Function: Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:23955153, PubMed:24025841, PubMed:7538907, PubMed:9184224). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:7538907, PubMed:9184224). Active CASP8 initiates the subsequent cascade of caspases mediating apoptosis (PubMed:16762833). Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling (PubMed:21109225, PubMed:24204270)\n Location: Cytoplasm\n Domains: DED; Death\n\nProtein 2: DYNC1H1 (Q14204, 4646 AA)\n Function: Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074)\n Location: Cytoplasm, cytoskeleton\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1376661, "gene_symbol_1": "FADD", "gene_symbol_2": "DYNC1H1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q13158", "uniprot_2": "Q14204"}} +{"question_id": "PPIL3-0026", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: CACNG1 (Q06432, 222 AA)\n Function: Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics\n Location: Cell membrane, sarcolemma\n Domains: None\n\nProtein 2: IL12RB2 (Q99665, 862 AA)\n Function: Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production\n Location: Membrane\n Domains: Fibronectin type-III 1; Fibronectin type-III 2; Fibronectin type-III 3; Fibronectin type-III 4; Fibronectin type-III 5\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1471369, "gene_symbol_1": "CACNG1", "gene_symbol_2": "IL12RB2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q06432", "uniprot_2": "Q99665"}} +{"question_id": "PPIL3-0027", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: CCNDBP1 (O95273, 360 AA)\n Function: May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription\n Location: Cytoplasm\n Domains: None\n\nProtein 2: EDF1 (O60869, 148 AA)\n Function: Transcriptional coactivator stimulating NR5A1 and ligand-dependent NR1H3/LXRA and PPARG transcriptional activities. Enhances the DNA-binding activity of ATF1, ATF2, CREB1 and NR5A1. Regulates nitric oxid synthase activity probably by sequestering calmodulin in the cytoplasm. May function in endothelial cells differentiation, hormone-induced cardiomyocytes hypertrophy and lipid metabolism\n Location: Cytoplasm\n Domains: HTH cro/C1-type\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 79567, "gene_symbol_1": "CCNDBP1", "gene_symbol_2": "EDF1", "detection_method": null, "compartment_type": "same", "uniprot_1": "O95273", "uniprot_2": "O60869"}} +{"question_id": "PPIL3-0028", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: SELL (P14151, 372 AA)\n Function: Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia (PubMed:12403782, PubMed:28011641)\n Location: Cell membrane\n Domains: C-type lectin; EGF-like; Sushi 1; Sushi 2\n\nProtein 2: ORC2 (Q13416, 577 AA)\n Function: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 162241, "gene_symbol_1": "SELL", "gene_symbol_2": "ORC2", "detection_method": null, "compartment_type": "different", "uniprot_1": "P14151", "uniprot_2": "Q13416"}} +{"question_id": "PPIL3-0029", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: COX6C (P09669, 75 AA)\n Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: TAF12 (Q16514, 161 AA)\n Function: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). Component of the TATA-binding protein-free TAF complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex (PubMed:10373431, PubMed:7729427, PubMed:8598932, PubMed:8663456, PubMed:9674425, PubMed:9885574)\n Location: Nucleus\n Domains: Histone-fold\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1669731, "gene_symbol_1": "COX6C", "gene_symbol_2": "TAF12", "detection_method": null, "compartment_type": "different", "uniprot_1": "P09669", "uniprot_2": "Q16514"}} +{"question_id": "PPIL3-0030", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: HOXC9 (P31274, 260 AA)\n Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis\n Location: Nucleus\n Domains: None\n\nProtein 2: CHAF1B (Q13112, 559 AA)\n Function: Acts as a component of the histone chaperone complex chromatin assembly factor 1 (CAF-1), which assembles histone octamers onto DNA during replication and repair. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 579447, "gene_symbol_1": "HOXC9", "gene_symbol_2": "CHAF1B", "detection_method": null, "compartment_type": "same", "uniprot_1": "P31274", "uniprot_2": "Q13112"}} +{"question_id": "PPIL3-0031", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: GLRX3 (O76003, 335 AA)\n Function: Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity\n Location: Cytoplasm, cytosol\n Domains: Glutaredoxin 1; Glutaredoxin 2; Thioredoxin\n\nProtein 2: CRBN (Q96SW2, 442 AA)\n Function: Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL (PubMed:26990986, PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:18414909, PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (PubMed:18414909). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). Plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, leading to inhibition of ECSIT ubiquitination, an important step of the signaling (PubMed:31620128)\n Location: Cytoplasm\n Domains: CULT; Lon N-terminal\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1077273, "gene_symbol_1": "GLRX3", "gene_symbol_2": "CRBN", "detection_method": null, "compartment_type": "same", "uniprot_1": "O76003", "uniprot_2": "Q96SW2"}} +{"question_id": "PPIL3-0032", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: EXOC5 (O00471, 708 AA)\n Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane\n Location: Cytoplasm\n Domains: None\n\nProtein 2: EIF4E (P06730, 217 AA)\n Function: Acts in the cytoplasm to initiate and regulate protein synthesis and is required in the nucleus for export of a subset of mRNAs from the nucleus to the cytoplasm which promotes processes such as RNA capping, processing and splicing (PubMed:11606200, PubMed:22578813, PubMed:22684010, PubMed:24335285, PubMed:29987188). Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (By similarity). This protein recognizes and binds the 7-methylguanosine (m7G)-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (PubMed:16271312, PubMed:22578813). Together with EIF4G1, antagonizes the scanning promoted by EIF1-EIF4G1 and is required for TISU translation, a process where the TISU element recognition makes scanning unnecessary (PubMed:29987188). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (PubMed:24335285). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap (By similarity). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (PubMed:24335285). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). As well as its roles in translation, also involved in mRNA nucleocytoplasmic transport (By similarity). Its role in mRNA export from the nucleus to the cytoplasm relies on its ability to bind the m7G cap of RNAs and on the presence of the 50-nucleotide EIF4E sensitivity element (4ESE) in the 3'UTR of sensitive transcripts (By similarity). Interaction with the 4ESE is mediated by LRPPRC which binds simultaneously to both EIF4E and the 4ESE, thereby acting as a platform for assembly for the RNA export complex (By similarity). EIF4E-dependent mRNA export is independent of ongoing protein or RNA synthesis and is also NFX1-independent but is XPO1-dependent with LRPPRC interacting with XPO1 to form an EIF4E-dependent mRNA export complex (By similarity). Alters the composition of the cytoplasmic face of the nuclear pore to promote RNA export by reducing RANBP2 expression, relocalizing nucleoporin NUP214 and increasing expression of RANBP1 and RNA export factors DDX19 and GLE1 (By similarity). Promotes the nuclear export of cyclin CCND1 mRNA (By similarity). Promotes the nuclear export of NOS2/iNOS mRNA (PubMed:23471078). Promotes the nuclear export of MDM2 mRNA (PubMed:22684010). Promotes the export of additional mRNAs, including others involved in the cell cycle (By similarity). In the nucleus, binds to capped splice factor-encoding mRNAs and stimulates their nuclear export to enhance splice factor production by increasing their cytoplasmic availability to the translation machinery (By similarity). May also regulate splicing through interaction with the spliceosome in an RNA and m7G cap-dependent manner (By similarity). Also binds to some pre-mRNAs and may play a role in their recruitment to the spliceosome (By similarity). Promotes steady-state capping of a subset of coding and non-coding RNAs by mediating nuclear export of capping machinery mRNAs including RNMT, RNGTT and RAMAC to enhance their translation (By similarity). Stimulates mRNA 3'-end processing by promoting the expression of several core cleavage complex factors required for mRNA cleavage and polyadenylation, and may also have a direct effect through its interaction with the CPSF3 cleavage enzyme (By similarity). Rescues cells from apoptosis by promoting activation of serine/threonine-protein kinase AKT1 through mRNA export of NBS1 which potentiates AKT1 phosphorylation and also through mRNA export of AKT1 effectors, allowing for increased production of these proteins (By similarity)\n Location: Cytoplasm, P-body\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 655964, "gene_symbol_1": "EXOC5", "gene_symbol_2": "EIF4E", "detection_method": null, "compartment_type": "same", "uniprot_1": "O00471", "uniprot_2": "P06730"}} +{"question_id": "PPIL3-0033", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: FADD (Q13158, 208 AA)\n Function: Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:23955153, PubMed:24025841, PubMed:7538907, PubMed:9184224). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:7538907, PubMed:9184224). Active CASP8 initiates the subsequent cascade of caspases mediating apoptosis (PubMed:16762833). Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling (PubMed:21109225, PubMed:24204270)\n Location: Cytoplasm\n Domains: DED; Death\n\nProtein 2: EIF3M (Q7L2H7, 374 AA)\n Function: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17403899, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17403899). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773)\n Location: Cytoplasm\n Domains: PCI\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1316280, "gene_symbol_1": "FADD", "gene_symbol_2": "EIF3M", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q13158", "uniprot_2": "Q7L2H7"}} +{"question_id": "PPIL3-0034", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: KRT18 (P05783, 430 AA)\n Function: Required for the formation of KRT8/KRT18 filaments that are involved in ARHGEF40-mediated actin stress fiber formation and tensional force-induced stress fiber formation and reinforcement (PubMed:26823019). Also acts downstream of ROCK kinase activation as part of a positive feedback mechanism in response to cellular mechanical stress loading (PubMed:26823019). Organization and orientation of KRT18 filaments are responsible for the properly elongated morphology of epithelial tubules (By similarity). Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection\n Location: Nucleus matrix\n Domains: IF rod\n\nProtein 2: MYBBP1A (Q9BQG0, 1328 AA)\n Function: May activate or repress transcription via interactions with sequence specific DNA-binding proteins (By similarity). Repression may be mediated at least in part by histone deacetylase activity (HDAC activity) (By similarity). Acts as a corepressor and in concert with CRY1, represses the transcription of the core circadian clock component PER2 (By similarity). Preferentially binds to dimethylated histone H3 'Lys-9' (H3K9me2) on the PER2 promoter (By similarity). Has a role in rRNA biogenesis together with PWP1 (PubMed:29065309)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1244423, "gene_symbol_1": "KRT18", "gene_symbol_2": "MYBBP1A", "detection_method": null, "compartment_type": "different", "uniprot_1": "P05783", "uniprot_2": "Q9BQG0"}} +{"question_id": "PPIL3-0035", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: RBBP5 (Q15291, 538 AA)\n Function: In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). Does not affect ES cell self-renewal (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (PubMed:19556245). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:19556245). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653)\n Location: Nucleus\n Domains: None\n\nProtein 2: CHMP4A (Q9BY43, 222 AA)\n Function: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413)\n Location: Cytoplasmic vesicle membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 549582, "gene_symbol_1": "RBBP5", "gene_symbol_2": "CHMP4A", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q15291", "uniprot_2": "Q9BY43"}} +{"question_id": "PPIL3-0036", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: CBLL1 (Q75N03, 491 AA)\n Function: E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (By similarity). Targets CDH1 for endocytosis and degradation (By similarity). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Its function in the WMM complex is unknown (PubMed:29507755)\n Location: Nucleus speckle\n Domains: None\n\nProtein 2: IFNL4 (K9M1U5, 179 AA)\n Function: Cytokine that may trigger an antiviral response activating the JAK-STAT pathway and up-regulating specifically some interferon-stimulated genes\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 649891, "gene_symbol_1": "CBLL1", "gene_symbol_2": "IFNL4", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q75N03", "uniprot_2": "K9M1U5"}} +{"question_id": "PPIL3-0037", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: ANXA2 (P07355, 339 AA)\n Function: Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity)\n Location: Secreted, extracellular space, extracellular matrix, basement membrane\n Domains: None\n\nProtein 2: PPP4R2 (Q9NY27, 417 AA)\n Function: Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4). May regulate the activity of PPP4C at centrosomal microtubule organizing centers. Its interaction with the SMN complex leads to enhance the temporal localization of snRNPs, suggesting a role of PPP4C in maturation of spliceosomal snRNPs. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on 'Ser-140' (gamma-H2AX) generated during DNA replication and required for DNA double strand break repair. Mediates RPA2 dephosphorylation by recruiting PPP4C to RPA2 in a DNA damage-dependent manner. RPA2 dephosphorylation is required for the efficient RPA2-mediated recruitment of RAD51 to chromatin following double strand breaks, an essential step for DNA repair\n Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1139237, "gene_symbol_1": "ANXA2", "gene_symbol_2": "PPP4R2", "detection_method": null, "compartment_type": "different", "uniprot_1": "P07355", "uniprot_2": "Q9NY27"}} +{"question_id": "PPIL3-0038", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: EIF3A (Q14152, 1382 AA)\n Function: RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:11169732, PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815)\n Location: Cytoplasm\n Domains: PCI\n\nProtein 2: BACH1 (O14867, 736 AA)\n Function: Transcriptional regulator that acts as a repressor or activator, depending on the context. Binds to NF-E2 DNA binding sites. Plays important roles in coordinating transcription activation and repression by MAFK (By similarity). Together with MAF, represses the transcription of genes under the control of the NFE2L2 oxidative stress pathway (PubMed:24035498)\n Location: Nucleus\n Domains: BTB; bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1331389, "gene_symbol_1": "EIF3A", "gene_symbol_2": "BACH1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q14152", "uniprot_2": "O14867"}} +{"question_id": "PPIL3-0039", "task": "ppi-l3", "split": "val", "difficulty": "medium", "context_text": "Protein 1: IMP3 (Q9NV31, 184 AA)\n Function: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing (PubMed:12655004). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797)\n Location: Nucleus, nucleolus\n Domains: S4 RNA-binding\n\nProtein 2: CCNL1 (Q9UK58, 526 AA)\n Function: Regulatory component of the cyclin-L-CDK11 complex that regulates transcription and pre-mRNA splicing (PubMed:11980906, PubMed:18216018, PubMed:38059508). Inhibited by the CDK-specific inhibitor CDKN1A/p21 (PubMed:11980906). May be a candidate proto-oncogene in head and neck squamous cell carcinomas (HNSCC) (PubMed:12414649, PubMed:15700036)\n Location: Nucleus speckle\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1463009, "gene_symbol_1": "IMP3", "gene_symbol_2": "CCNL1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9NV31", "uniprot_2": "Q9UK58"}} +{"question_id": "PPIL3-0040", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BCL2L1 (Q07817, 233 AA)\n Function: Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: ABCB8 (Q9NUT2, 735 AA)\n Function: ATP-binding subunit of the mitochondrial ATP-gated potassium channel (mitoK(ATP)) (PubMed:31435016). Together with pore-forming subunit CCDC51/MITOK of the mitoK(ATP) channel, mediates ATP-dependent potassium currents across the mitochondrial inner membrane (PubMed:31435016). An increase in ATP intracellular levels closes the channel, inhibiting K(+) transport, whereas a decrease in ATP levels enhances K(+) uptake in the mitochondrial matrix (PubMed:31435016). Plays a role in mitochondrial iron transport (PubMed:30623799). Required for maintenance of normal cardiac function, possibly by influencing mitochondrial iron export and regulating the maturation of cytosolic iron sulfur cluster-containing enzymes (By similarity)\n Location: Mitochondrion inner membrane\n Domains: ABC transmembrane type-1; ABC transporter\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 511522, "gene_symbol_1": "BCL2L1", "gene_symbol_2": "ABCB8", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q07817", "uniprot_2": "Q9NUT2"}} +{"question_id": "PPIL3-0041", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: OOEP (A6NGQ2, 149 AA)\n Function: Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development. The SCMC complex is a structural constituent of cytoplasmic lattices, which consist in fibrous structures found in the cytoplasm of oocytes and preimplantation embryos. They are required to store maternal proteins critical for embryonic development, such as proteins that control epigenetic reprogramming of the preimplantation embryo, and prevent their degradation or activation. As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25 to DNA replication forks, thereby promoting the ubiquitination of BLM by TRIM25, enhancing BLM retainment at replication forks and therefore promoting stalled replication fork restart. Positively regulates the homologous recombination-mediated DNA double-strand break (DSB) repair pathway by regulating ATM activation and RAD51 recruitment to DSBs in oocytes. Thereby contributes to oocyte survival and the resumption and completion of meiosis\n Location: Cytoplasm\n Domains: KH; atypical\n\nProtein 2: PIGC (Q92535, 297 AA)\n Function: Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 840819, "gene_symbol_1": "OOEP", "gene_symbol_2": "PIGC", "detection_method": null, "compartment_type": "different", "uniprot_1": "A6NGQ2", "uniprot_2": "Q92535"}} +{"question_id": "PPIL3-0042", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SRSF9 (Q13242, 221 AA)\n Function: Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10\n Location: Nucleus\n Domains: RRM 1; RRM 2\n\nProtein 2: TPX2 (Q9ULW0, 747 AA)\n Function: Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules (PubMed:18663142, PubMed:19208764, PubMed:37728657). Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation (PubMed:18663142, PubMed:19208764). TPX2 is inactivated upon binding to importin-alpha (PubMed:26165940). At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation (PubMed:26165940)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 294418, "gene_symbol_1": "SRSF9", "gene_symbol_2": "TPX2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q13242", "uniprot_2": "Q9ULW0"}} +{"question_id": "PPIL3-0043", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BAZ1B (Q9UIG0, 1483 AA)\n Function: Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802, PubMed:19234442). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802, PubMed:19234442). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (PubMed:28801535). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (PubMed:15543136)\n Location: Nucleus\n Domains: Bromo; DDT; WAC\n\nProtein 2: SMC4 (Q9NTJ3, 1288 AA)\n Function: Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases\n Location: Nucleus\n Domains: SMC hinge\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1181381, "gene_symbol_1": "BAZ1B", "gene_symbol_2": "SMC4", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9UIG0", "uniprot_2": "Q9NTJ3"}} +{"question_id": "PPIL3-0044", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MCM5 (P33992, 734 AA)\n Function: Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells (PubMed:40940420). Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425)\n Location: Nucleus\n Domains: MCM C-terminal AAA(+) ATPase\n\nProtein 2: MCL1 (Q07820, 350 AA)\n Function: Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis\n Location: Membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1220086, "gene_symbol_1": "MCM5", "gene_symbol_2": "MCL1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P33992", "uniprot_2": "Q07820"}} +{"question_id": "PPIL3-0045", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BAD (Q92934, 168 AA)\n Function: Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways\n Location: Mitochondrion outer membrane\n Domains: None\n\nProtein 2: MIS18BP1 (Q6P0N0, 1132 AA)\n Function: Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis\n Location: Nucleus\n Domains: SANT; SANTA\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1451012, "gene_symbol_1": "BAD", "gene_symbol_2": "MIS18BP1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q92934", "uniprot_2": "Q6P0N0"}} +{"question_id": "PPIL3-0046", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ASAP2 (O43150, 1006 AA)\n Function: Activates the small GTPases ARF1, ARF5 and ARF6. Regulates the formation of post-Golgi vesicles and modulates constitutive secretion. Modulates phagocytosis mediated by Fc gamma receptor and ARF6. Modulates PXN recruitment to focal contacts and cell migration\n Location: Cytoplasm\n Domains: Arf-GAP; PH; SH3\n\nProtein 2: STRAP (Q9Y3F4, 350 AA)\n Function: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 56624, "gene_symbol_1": "ASAP2", "gene_symbol_2": "STRAP", "detection_method": null, "compartment_type": "same", "uniprot_1": "O43150", "uniprot_2": "Q9Y3F4"}} +{"question_id": "PPIL3-0047", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: EXOSC2 (Q13868, 293 AA)\n Function: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC2 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC4 and EXOSC7\n Location: Cytoplasm\n Domains: S1 motif\n\nProtein 2: CCT8 (P50990, 548 AA)\n Function: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1611658, "gene_symbol_1": "EXOSC2", "gene_symbol_2": "CCT8", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q13868", "uniprot_2": "P50990"}} +{"question_id": "PPIL3-0048", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: KNTC1 (P50748, 2209 AA)\n Function: Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores (PubMed:11146660, PubMed:11590237, PubMed:15824131). Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex\n Location: Cytoplasm\n Domains: None\n\nProtein 2: TERF2 (Q15554, 542 AA)\n Function: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes (PubMed:15608617, PubMed:16166375, PubMed:20655466, PubMed:28216226, PubMed:31595153, PubMed:9326950, PubMed:9326951, PubMed:9476899). In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo (PubMed:16166375, PubMed:20655466). Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection (PubMed:16166375). Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways (PubMed:16166375). Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair (PubMed:20655466). Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo (PubMed:20655466, PubMed:28216226). Preferentially binds to positive supercoiled DNA (PubMed:15608617, PubMed:20655466). Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology (PubMed:20655466). Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length (By similarity)\n Location: Nucleus\n Domains: HTH myb-type\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1103763, "gene_symbol_1": "KNTC1", "gene_symbol_2": "TERF2", "detection_method": null, "compartment_type": "different", "uniprot_1": "P50748", "uniprot_2": "Q15554"}} +{"question_id": "PPIL3-0049", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MED14 (O60244, 1454 AA)\n Function: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors\n Location: Nucleus\n Domains: None\n\nProtein 2: SLF1 (Q9BQI6, 1058 AA)\n Function: Plays a role in the DNA damage response (DDR) pathway by regulating postreplication repair of UV-damaged DNA and genomic stability maintenance (PubMed:25931565). The SLF1-SLF2 complex acts to link RAD18 with the SMC5-SMC6 complex at replication-coupled interstrand cross-links (ICL) and DNA double-strand breaks (DSBs) sites on chromatin during DNA repair in response to stalled replication forks (PubMed:25931565). Promotes the recruitment of SLF2 and the SMC5-SMC6 complex to DNA lesions (PubMed:25931565, PubMed:36373674)\n Location: Nucleus\n Domains: BRCT 1; BRCT 2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 805386, "gene_symbol_1": "MED14", "gene_symbol_2": "SLF1", "detection_method": null, "compartment_type": "same", "uniprot_1": "O60244", "uniprot_2": "Q9BQI6"}} +{"question_id": "PPIL3-0050", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SLC1A1 (P43005, 524 AA)\n Function: Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:21123949, PubMed:26690923, PubMed:33658209, PubMed:7521911, PubMed:7914198, PubMed:8857541). Can also transport L-cysteine (PubMed:21123949). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:26690923, PubMed:33658209, PubMed:7521911, PubMed:8857541). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:26690923, PubMed:8857541). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:21123949). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity). Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport (By similarity). Negatively regulated by ARL6IP5 (By similarity)\n Location: Cell membrane\n Domains: None\n\nProtein 2: TOB2 (Q14106, 344 AA)\n Function: Anti-proliferative protein inhibits cell cycle progression from the G0/G1 to S phases\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 216798, "gene_symbol_1": "SLC1A1", "gene_symbol_2": "TOB2", "detection_method": null, "compartment_type": "different", "uniprot_1": "P43005", "uniprot_2": "Q14106"}} +{"question_id": "PPIL3-0051", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: INSR (P06213, 1382 AA)\n Function: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity)\n Location: Cell membrane\n Domains: Fibronectin type-III 1; Fibronectin type-III 2; Fibronectin type-III 3; Protein kinase\n\nProtein 2: AKIP1 (Q9NQ31, 210 AA)\n Function: Enhances NF-kappa-B transcriptional activity by regulating the nuclear localization of the NF-kappa-B subunit RELA and promoting the phosphorylation of RELA by PRKACA. Regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 133634, "gene_symbol_1": "INSR", "gene_symbol_2": "AKIP1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P06213", "uniprot_2": "Q9NQ31"}} +{"question_id": "PPIL3-0052", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: DNAAF11 (Q86X45, 466 AA)\n Function: Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia (PubMed:23122589, PubMed:23527195, PubMed:33403504). Acts as a crucial component in the formation and motility of spermatozoal flagella (PubMed:33403504)\n Location: Cytoplasm\n Domains: CS; LRRCT\n\nProtein 2: AK8 (Q96MA6, 479 AA)\n Function: Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. Also displays broad nucleoside diphosphate kinase activity\n Location: Cytoplasm, cytosol\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 399069, "gene_symbol_1": "DNAAF11", "gene_symbol_2": "AK8", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q86X45", "uniprot_2": "Q96MA6"}} +{"question_id": "PPIL3-0053", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: LSM5 (Q9Y4Y9, 91 AA)\n Function: Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320)\n Location: Nucleus\n Domains: Sm\n\nProtein 2: NACA (Q13765, 215 AA)\n Function: Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters\n Location: Cytoplasm\n Domains: NAC-A/B; UBA\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1413799, "gene_symbol_1": "LSM5", "gene_symbol_2": "NACA", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9Y4Y9", "uniprot_2": "Q13765"}} +{"question_id": "PPIL3-0054", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SLC16A13 (Q7RTY0, 426 AA)\n Function: Proton-linked monocarboxylate transporter. May catalyze the transport of monocarboxylates across the plasma membrane\n Location: Golgi apparatus membrane\n Domains: None\n\nProtein 2: KCTD6 (Q8NC69, 237 AA)\n Function: Probable substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes the ubiquitination of HDAC1; the function seems to depend on KCTD11:KCTD6 oligomerization. Can function as antagonist of the Hedgehog pathway by affecting the nuclear transfer of transcription factor GLI1; the function probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. Inhibits cell growth and tumorigenicity of medulloblastoma (MDB) (PubMed:21472142). Involved in regulating protein levels of ANK1 isoform Mu17 probably implicating CUL3-dependent proteasomal degradation (PubMed:22573887)\n Location: Cytoplasm, myofibril, sarcomere, M line\n Domains: BTB\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 387554, "gene_symbol_1": "SLC16A13", "gene_symbol_2": "KCTD6", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q7RTY0", "uniprot_2": "Q8NC69"}} +{"question_id": "PPIL3-0055", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: COX5A (P20674, 150 AA)\n Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: AP2S1 (P53680, 142 AA)\n Function: Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). May also play a role in extracellular calcium homeostasis\n Location: Cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1692865, "gene_symbol_1": "COX5A", "gene_symbol_2": "AP2S1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P20674", "uniprot_2": "P53680"}} +{"question_id": "PPIL3-0056", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: GEMIN2 (O14893, 280 AA)\n Function: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:18984161, PubMed:9323129). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (PubMed:18984161). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG (5Sm) are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:18984161). To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A (PubMed:18984161, PubMed:9323129). Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (PubMed:31799625). Within the SMN complex, GEMIN2 constrains the conformation of 5Sm, thereby promoting 5Sm binding to snRNA containing the snRNP code (a nonameric Sm site and a 3'-adjacent stem-loop), thus preventing progression of assembly until a cognate substrate is bound (PubMed:16314521, PubMed:21816274, PubMed:31799625)\n Location: Nucleus, gem\n Domains: None\n\nProtein 2: BORCS5 (Q969J3, 196 AA)\n Function: As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor. Thereby, it may indirectly play a role in cell spreading and motility\n Location: Lysosome membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1357206, "gene_symbol_1": "GEMIN2", "gene_symbol_2": "BORCS5", "detection_method": null, "compartment_type": "different", "uniprot_1": "O14893", "uniprot_2": "Q969J3"}} +{"question_id": "PPIL3-0057", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ACTB (P60709, 375 AA)\n Function: Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity)\n Location: Cytoplasm, cytoskeleton\n Domains: None\n\nProtein 2: TTI1 (O43156, 1089 AA)\n Function: Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 890047, "gene_symbol_1": "ACTB", "gene_symbol_2": "TTI1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P60709", "uniprot_2": "O43156"}} +{"question_id": "PPIL3-0058", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BIRC5 (O15392, 142 AA)\n Function: Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:20627126, PubMed:21364656, PubMed:25778398, PubMed:28218735, PubMed:9859993). Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (PubMed:16322459). Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (PubMed:20826784). Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (PubMed:20929775). The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). May counteract a default induction of apoptosis in G2/M phase (PubMed:9859993). The acetylated form represses STAT3 transactivation of target gene promoters (PubMed:20826784). May play a role in neoplasia (PubMed:10626797). Inhibitor of CASP3 and CASP7 (PubMed:21536684). Essential for the maintenance of mitochondrial integrity and function (PubMed:25778398). Isoform 2 and isoform 3 do not appear to play vital roles in mitosis (PubMed:12773388, PubMed:16291752). Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform (PubMed:10626797)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: RAD51 (Q06609, 339 AA)\n Function: Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:22325354, PubMed:23509288, PubMed:23754376, PubMed:26681308, PubMed:28575658, PubMed:32640219). Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange (PubMed:12205100, PubMed:18417535, PubMed:15226506, PubMed:20231364, PubMed:20348101, PubMed:23509288, PubMed:23754376, PubMed:26681308, PubMed:28575658). Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:23509288, PubMed:23754376, PubMed:26681308, PubMed:28575658, PubMed:38459011). Recruited to resolve stalled replication forks during replication stress (PubMed:27797818, PubMed:31844045). Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR (PubMed:12442171, PubMed:24141787). Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3 (PubMed:20413593). Also involved in interstrand cross-link repair (PubMed:26253028)\n Location: Nucleus\n Domains: HhH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 682916, "gene_symbol_1": "BIRC5", "gene_symbol_2": "RAD51", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15392", "uniprot_2": "Q06609"}} +{"question_id": "PPIL3-0059", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: IKBKG (Q9Y6K9, 419 AA)\n Function: Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:14695475, PubMed:20724660, PubMed:21518757, PubMed:9751060). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:19185524, PubMed:21606507, PubMed:27777308, PubMed:33567255). Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:19185524, PubMed:21606507, PubMed:27777308). Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3 (PubMed:19854139). Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (PubMed:20724660)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: ULK1 (O75385, 1050 AA)\n Function: Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165, PubMed:39384743). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708)\n Location: Cytoplasm, cytosol\n Domains: Protein kinase\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1511462, "gene_symbol_1": "IKBKG", "gene_symbol_2": "ULK1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9Y6K9", "uniprot_2": "O75385"}} +{"question_id": "PPIL3-0060", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RAD50 (Q92878, 1312 AA)\n Function: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28134932, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:15064416, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:11741547, PubMed:9590181, PubMed:9651580, PubMed:9705271). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:11741547, PubMed:12805565, PubMed:28134932). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888)\n Location: Nucleus\n Domains: Zinc-hook\n\nProtein 2: SPTLC1 (O15269, 473 AA)\n Function: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1133601, "gene_symbol_1": "RAD50", "gene_symbol_2": "SPTLC1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q92878", "uniprot_2": "O15269"}} +{"question_id": "PPIL3-0061", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MCM7 (P33993, 719 AA)\n Function: Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for S-phase checkpoint activation upon UV-induced damage\n Location: Nucleus\n Domains: MCM C-terminal AAA(+) ATPase\n\nProtein 2: RNASEH2A (O75792, 299 AA)\n Function: Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes\n Location: Nucleus\n Domains: RNase H type-2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1437327, "gene_symbol_1": "MCM7", "gene_symbol_2": "RNASEH2A", "detection_method": null, "compartment_type": "same", "uniprot_1": "P33993", "uniprot_2": "O75792"}} +{"question_id": "PPIL3-0062", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: USF2 (Q15853, 346 AA)\n Function: Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters\n Location: Nucleus\n Domains: bHLH\n\nProtein 2: SMC2 (O95347, 1197 AA)\n Function: Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases\n Location: Nucleus\n Domains: SMC hinge\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1530451, "gene_symbol_1": "USF2", "gene_symbol_2": "SMC2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q15853", "uniprot_2": "O95347"}} +{"question_id": "PPIL3-0063", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: KCNH2 (Q12809, 1159 AA)\n Function: Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)\n Location: Cell membrane\n Domains: PAC; PAS\n\nProtein 2: ATP6V1E1 (P36543, 226 AA)\n Function: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:32001091, PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091)\n Location: Apical cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 915758, "gene_symbol_1": "KCNH2", "gene_symbol_2": "ATP6V1E1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q12809", "uniprot_2": "P36543"}} +{"question_id": "PPIL3-0064", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CDK5 (Q00535, 292 AA)\n Function: Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Negatively regulates the CACNA1B/CAV2.2 -mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in postmitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Also phosphorylates exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-BMAL1 heterodimer in association with altered stability and subcellular distribution\n Location: Cytoplasm\n Domains: Protein kinase\n\nProtein 2: ATP6V1C1 (P21283, 382 AA)\n Function: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity (By similarity)\n Location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 537846, "gene_symbol_1": "CDK5", "gene_symbol_2": "ATP6V1C1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q00535", "uniprot_2": "P21283"}} +{"question_id": "PPIL3-0065", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SNRPE (P62304, 92 AA)\n Function: Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23246290, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:28781166). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077). As part of the U7 snRNP it is involved in histone 3'-end processing (PubMed:12975319)\n Location: Cytoplasm, cytosol\n Domains: Sm\n\nProtein 2: USP22 (Q9UPT9, 525 AA)\n Function: Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity. As part of the transcription regulatory histone acetylation (HAT) complex SAGA, catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a transcriptional coactivator (PubMed:18206972, PubMed:18206973, PubMed:18469533). Recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Facilitates cell-cycle progression by stabilizing CCNB1 and antagonizing its proteasome-mediated degradation in a cell cycle-specific manner (PubMed:27030811). Modulates cell cycle progression and apoptosis also by antagonizing TP53 transcriptional activation through deacetylase SIRT1 stabilization (PubMed:22542455). Plays multiple roles in immunity and inflammation. Participates in antiviral response by deubiquitinating the importin KPNA2, leading to IRF3 nuclear translocation and subsequent type I interferon production (PubMed:32130408). Acts as a central regulator of type III IFN signaling by negatively regulating STING1 activation and ubiquitination (PubMed:35933402). Inhibits NLRP3 inflammasome activation by promoting NLRP3 degradation through ATG5-dependent autophagy (By similarity). Deubiquitinates CD274 to induce its stabilization and thereby participates in maintenance of immune tolerance to self (PubMed:31399419). Controls necroptotic cell death by regulating RIPK3 phosphorylation and ubiquitination (PubMed:33369872). During bacterial infection, promotes pro-inflammatory response by targeting TRAF6 and removing its 'Lys-48'-linked polyubiquitination (By similarity)\n Location: Nucleus\n Domains: USP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 924937, "gene_symbol_1": "SNRPE", "gene_symbol_2": "USP22", "detection_method": null, "compartment_type": "different", "uniprot_1": "P62304", "uniprot_2": "Q9UPT9"}} +{"question_id": "PPIL3-0066", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TINF2 (Q9BSI4, 451 AA)\n Function: Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Plays a role in shelterin complex assembly. Isoform 1 may have additional role in tethering telomeres to the nuclear matrix\n Location: Nucleus\n Domains: None\n\nProtein 2: L3MBTL1 (Q9Y468, 840 AA)\n Function: Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, thereby acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/H1-4 at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1052138, "gene_symbol_1": "TINF2", "gene_symbol_2": "L3MBTL1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9BSI4", "uniprot_2": "Q9Y468"}} +{"question_id": "PPIL3-0067", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NXF3 (Q9H4D5, 531 AA)\n Function: May function as a tissue-specific nuclear mRNA export factor\n Location: Nucleus\n Domains: NTF2; RRM\n\nProtein 2: AP3S1 (Q92572, 193 AA)\n Function: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals\n Location: Golgi apparatus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1630577, "gene_symbol_1": "NXF3", "gene_symbol_2": "AP3S1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9H4D5", "uniprot_2": "Q92572"}} +{"question_id": "PPIL3-0068", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ZC3H11A (O75152, 810 AA)\n Function: Through its association with TREX complex components, may participate in the export and post-transcriptional coordination of selected mRNA transcripts, including those required to maintain the metabolic processes in embryonic cells (PubMed:22928037, PubMed:37356722). Binds RNA (PubMed:29610341, PubMed:37356722)\n Location: Nucleus\n Domains: None\n\nProtein 2: KAT6B (Q8WYB5, 2073 AA)\n Function: Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity\n Location: Nucleus\n Domains: H15; MYST-type HAT; SAMD1-like winged helix (WH)\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 754840, "gene_symbol_1": "ZC3H11A", "gene_symbol_2": "KAT6B", "detection_method": null, "compartment_type": "same", "uniprot_1": "O75152", "uniprot_2": "Q8WYB5"}} +{"question_id": "PPIL3-0069", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: LDHA (P00338, 332 AA)\n Function: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: AP4S1 (Q9Y587, 144 AA)\n Function: Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable)\n Location: Golgi apparatus, trans-Golgi network membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 875172, "gene_symbol_1": "LDHA", "gene_symbol_2": "AP4S1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P00338", "uniprot_2": "Q9Y587"}} +{"question_id": "PPIL3-0070", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SMARCD2 (Q92925, 531 AA)\n Function: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:22952240, PubMed:26601204). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (PubMed:28369036)\n Location: Nucleus\n Domains: SWIB/MDM2\n\nProtein 2: FANCE (Q9HB96, 536 AA)\n Function: As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair. Required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 742856, "gene_symbol_1": "SMARCD2", "gene_symbol_2": "FANCE", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q92925", "uniprot_2": "Q9HB96"}} +{"question_id": "PPIL3-0071", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NBAS (A2RRP1, 2371 AA)\n Function: Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER (PubMed:19369418). Required for normal embryonic development (By similarity). May play a role in the nonsense-mediated decay pathway of mRNAs containing premature stop codons (By similarity)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: ATP8A2 (Q9NTI2, 1188 AA)\n Function: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (By similarity). Able to translocate phosphatidylserine, but not phosphatidylcholine (PubMed:34403372). Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules (By similarity). Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE) (By similarity). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP (By similarity). ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth (By similarity). Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes (By similarity). May be involved in vesicle trafficking in neuronal cells (By similarity). Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival (By similarity)\n Location: Membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1396637, "gene_symbol_1": "NBAS", "gene_symbol_2": "ATP8A2", "detection_method": null, "compartment_type": "different", "uniprot_1": "A2RRP1", "uniprot_2": "Q9NTI2"}} +{"question_id": "PPIL3-0072", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: IFT88 (Q13099, 824 AA)\n Function: Positively regulates primary cilium biogenesis (PubMed:17604723). Also involved in autophagy since it is required for trafficking of ATG16L and the expansion of the autophagic compartment\n Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole\n Domains: None\n\nProtein 2: MICOS10 (Q5TGZ0, 78 AA)\n Function: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane\n Location: Mitochondrion inner membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1265369, "gene_symbol_1": "IFT88", "gene_symbol_2": "MICOS10", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q13099", "uniprot_2": "Q5TGZ0"}} +{"question_id": "PPIL3-0073", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SFXN5 (Q8TD22, 340 AA)\n Function: Mitochondrial amino-acid transporter (By similarity). Transports citrate (By similarity). Does not act as a serine transporter: not able to mediate transport of serine into mitochondria (By similarity) (PubMed:30442778). In brown adipose tissue, plays a role in the regulation of UCP1-dependent thermogenesis probably by supporting mitochondrial glycerol-3-phosphate utilization (By similarity)\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: SLC25A18 (Q9H1K4, 315 AA)\n Function: Responsible for the transport of glutamate from the cytosol into the mitochondrial matrix with the concomitant import of a proton (symport system)\n Location: Mitochondrion inner membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 435602, "gene_symbol_1": "SFXN5", "gene_symbol_2": "SLC25A18", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q8TD22", "uniprot_2": "Q9H1K4"}} +{"question_id": "PPIL3-0074", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RIPK1 (Q13546, 671 AA)\n Function: Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:17703191, PubMed:24144979, PubMed:31827280, PubMed:31827281, PubMed:32657447, PubMed:35831301). Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (By similarity). Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (By similarity). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity). In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). Phosphorylates DAB2IP at 'Ser-728' in a TNF-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:15310755, PubMed:17389591). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity)\n Location: Cytoplasm\n Domains: Death; Protein kinase\n\nProtein 2: NFIL3 (Q16649, 462 AA)\n Function: Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites. Represses promoter activity in osteoblasts (By similarity). Represses transcriptional activity of PER1 (By similarity). Represses transcriptional activity of PER2 via the B-site on the promoter (By similarity). Activates transcription from the interleukin-3 promoter in T-cells. Competes for the same consensus-binding site with PAR DNA-binding factors (DBP, HLF and TEF) (By similarity). Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock (By similarity). Protects pro-B cells from programmed cell death (By similarity). Represses the transcription of CYP2A5 (By similarity). Positively regulates the expression and activity of CES2 by antagonizing the repressive action of NR1D1 on CES2 (By similarity). Required for the development of natural killer cell precursors (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1711203, "gene_symbol_1": "RIPK1", "gene_symbol_2": "NFIL3", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q13546", "uniprot_2": "Q16649"}} +{"question_id": "PPIL3-0075", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NSG1 (P42857, 185 AA)\n Function: Plays a role in the recycling mechanism in neurons of multiple receptors, including AMPAR, APP and L1CAM and acts at the level of early endosomes to promote sorting of receptors toward a recycling pathway. Regulates sorting and recycling of GRIA2 through interaction with GRIP1 and then contributes to the regulation of synaptic transmission and plasticity by affecting the recycling and targeting of AMPA receptors to the synapse (By similarity). Is required for faithful sorting of L1CAM to axons by facilitating trafficking from somatodendritic early endosome or the recycling endosome (By similarity). In an other hand, induces apoptosis via the activation of CASP3 in response to DNA damage (PubMed:20599942, PubMed:20878061)\n Location: Membrane\n Domains: None\n\nProtein 2: DYNLRB1 (Q9NP97, 96 AA)\n Function: Component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Required for structural and functional integrity of cilia (By similarity). Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (Probable). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (Probable)\n Location: Cytoplasm, cytoskeleton\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 216614, "gene_symbol_1": "NSG1", "gene_symbol_2": "DYNLRB1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P42857", "uniprot_2": "Q9NP97"}} +{"question_id": "PPIL3-0076", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CCT4 (P50991, 539 AA)\n Function: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: CNOT6 (Q9ULM6, 557 AA)\n Function: Poly(A) nuclease with 3'-5' RNase activity. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in mRNA decay mediated by the major-protein-coding determinant of instability (mCRD) of the FOS gene in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA. The increase of ligand-dependent ESR1-mediated transcription is much smaller, if any. Mediates cell proliferation and cell survival and prevents cellular senescence\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1322965, "gene_symbol_1": "CCT4", "gene_symbol_2": "CNOT6", "detection_method": null, "compartment_type": "same", "uniprot_1": "P50991", "uniprot_2": "Q9ULM6"}} +{"question_id": "PPIL3-0077", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TIMM21 (Q9BVV7, 248 AA)\n Function: Participates in the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Also required for assembly of mitochondrial respiratory chain complex I and complex IV as component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex. Probably shuttles between the presequence translocase and respiratory-chain assembly intermediates in a process that promotes incorporation of early nuclear-encoded subunits into these complexes\n Location: Mitochondrion membrane\n Domains: None\n\nProtein 2: MAFB (Q9Y5Q3, 323 AA)\n Function: Acts as a transcriptional activator or repressor (PubMed:27181683). Plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, osteoclast, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter (By similarity). Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Required for the transcriptional activation of HOXB3 in the rhombomere r5 in the hindbrain (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1146098, "gene_symbol_1": "TIMM21", "gene_symbol_2": "MAFB", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9BVV7", "uniprot_2": "Q9Y5Q3"}} +{"question_id": "PPIL3-0078", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: DDX54 (Q8TDD1, 881 AA)\n Function: Nucleolar RNA helicase that is involved in diverse cellular processes including ribosome biogenesis, DNA damage response, RNA splicing, transcriptional regulation, innate immunity, and nervous system development. Plays an essential role in the formation of the ribosome active site by remodeling rRNA structure and initiating peptidyl transferase center formation (PubMed:38632236). Represses the transcriptional activity of several nuclear receptors. Regulates transcriptome dynamics during DNA damage response. Mechanistically, acts via increased interaction with a well-defined class of pre-mRNAs that contain introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex. These activities lead to reduced intron retention and enhanced processing rates of its target transcripts (PubMed:28596291). Acts as an inhibitor of type I interferon antiviral response by facilitating ALKBH5-mediated demethylation of specific transcripts (PubMed:40793791). Contributes to central nervous system myelination, likely through regulation of oligodendrocyte differentiation and myelin sheath formation (By similarity)\n Location: Nucleus, nucleolus\n Domains: Helicase ATP-binding; Helicase C-terminal\n\nProtein 2: GABRQ (Q9UN88, 632 AA)\n Function: Theta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:10449790, PubMed:16412217). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:10449790, PubMed:16412217)\n Location: Postsynaptic cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 435972, "gene_symbol_1": "DDX54", "gene_symbol_2": "GABRQ", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q8TDD1", "uniprot_2": "Q9UN88"}} +{"question_id": "PPIL3-0079", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: PLAT (P00750, 562 AA)\n Function: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy (By similarity)\n Location: Secreted, extracellular space\n Domains: EGF-like; Fibronectin type-I; Kringle 1; Kringle 2; Peptidase S1\n\nProtein 2: BBS9 (Q3SYG4, 887 AA)\n Function: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. Required for proper BBSome complex assembly and its ciliary localization\n Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 593789, "gene_symbol_1": "PLAT", "gene_symbol_2": "BBS9", "detection_method": null, "compartment_type": "different", "uniprot_1": "P00750", "uniprot_2": "Q3SYG4"}} +{"question_id": "PPIL3-0080", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ITGA10 (O75578, 1167 AA)\n Function: Integrin alpha-10/beta-1 is a receptor for collagen\n Location: Membrane\n Domains: VWFA\n\nProtein 2: CHRNA2 (Q15822, 529 AA)\n Function: Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:18723036). CHRNA2 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4 and plays a role in nicotine dependence (PubMed:24467848, PubMed:27493220)\n Location: Synaptic cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1546113, "gene_symbol_1": "ITGA10", "gene_symbol_2": "CHRNA2", "detection_method": null, "compartment_type": "same", "uniprot_1": "O75578", "uniprot_2": "Q15822"}} +{"question_id": "PPIL3-0081", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NFYB (P25208, 207 AA)\n Function: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors\n Location: Nucleus\n Domains: None\n\nProtein 2: POLE3 (Q9NRF9, 147 AA)\n Function: Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity). Forms a complex with CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1 (PubMed:10801849). Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex (PubMed:14759371)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1073695, "gene_symbol_1": "NFYB", "gene_symbol_2": "POLE3", "detection_method": null, "compartment_type": "same", "uniprot_1": "P25208", "uniprot_2": "Q9NRF9"}} +{"question_id": "PPIL3-0082", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CHMP4A (Q9BY43, 222 AA)\n Function: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413)\n Location: Cytoplasmic vesicle membrane\n Domains: None\n\nProtein 2: GPRC5D (Q9NZD1, 345 AA)\n Function: G-protein coupled receptor involved in hard keratin expression and likely plays a role in the development of hair and nails\n Location: Cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 481254, "gene_symbol_1": "CHMP4A", "gene_symbol_2": "GPRC5D", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9BY43", "uniprot_2": "Q9NZD1"}} +{"question_id": "PPIL3-0083", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: DCP1A (Q9NPI6, 582 AA)\n Function: Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:12417715). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12417715). Contributes to the transactivation of target genes after stimulation by TGFB1 (PubMed:11836524). Essential for embryonic development (PubMed:33813271)\n Location: Cytoplasm, P-body\n Domains: None\n\nProtein 2: GABRA6 (Q16445, 453 AA)\n Function: Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:8632757). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity). Alpha-6/GABRA6 subunits are found at both synaptic and extrasynaptic sites (PubMed:8632757). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). Extrasynaptic alpha-6-containing receptors contribute to the tonic GABAergic inhibition. Alpha-6 subunits are also present on glutamatergic synapses (By similarity)\n Location: Postsynaptic cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 507687, "gene_symbol_1": "DCP1A", "gene_symbol_2": "GABRA6", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9NPI6", "uniprot_2": "Q16445"}} +{"question_id": "PPIL3-0084", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TNFSF14 (O43557, 240 AA)\n Function: Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Acts as a ligand for TNFRSF14/HVEM (PubMed:10754304, PubMed:9462508). Upon binding to TNFRSF14/HVEM, delivers costimulatory signals to T cells, leading to T cell proliferation and IFNG production (PubMed:10754304)\n Location: Cell membrane\n Domains: THD\n\nProtein 2: ARIH2 (O95376, 493 AA)\n Function: E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655, PubMed:33268465, PubMed:34518685, PubMed:38418882). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (PubMed:33268465, PubMed:34518685, PubMed:38418882). The initial ubiquitin is then elongated (PubMed:33268465). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the cullin-5 (CUL5) component of the ECS complex (PubMed:24076655). Together with the ECS(ASB9) complex, catalyzes ubiquitination of CKB (PubMed:33268465). Promotes ubiquitination of DCUN1D1 (PubMed:30587576). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 62514, "gene_symbol_1": "TNFSF14", "gene_symbol_2": "ARIH2", "detection_method": null, "compartment_type": "different", "uniprot_1": "O43557", "uniprot_2": "O95376"}} +{"question_id": "PPIL3-0085", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TSC1 (Q92574, 1164 AA)\n Function: Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155)\n Location: Lysosome membrane\n Domains: None\n\nProtein 2: EMC10 (Q5UCC4, 262 AA)\n Function: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:29242231, PubMed:29809151, PubMed:30415835, PubMed:32439656, PubMed:32459176). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:29242231, PubMed:29809151, PubMed:30415835). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:29809151, PubMed:30415835). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29242231, PubMed:29809151). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable). Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways (PubMed:28931551)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1204566, "gene_symbol_1": "TSC1", "gene_symbol_2": "EMC10", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q92574", "uniprot_2": "Q5UCC4"}} +{"question_id": "PPIL3-0086", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SMARCA5 (O60264, 1052 AA)\n Function: ATPase that possesses intrinsic ATP-dependent nucleosome-remodeling activity (PubMed:12972596, PubMed:28801535). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair; this may require intact histone H4 tails (PubMed:10880450, PubMed:12198550, PubMed:12434153, PubMed:12972596, PubMed:23911928, PubMed:28801535). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:28801535). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (PubMed:28801535). The BAZ1A/ACF1-, BAZ1B/WSTF-, BAZ2A/TIP5- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner (PubMed:14759371, PubMed:15543136, PubMed:28801535). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Binds to core histones together with RSF1, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Involved in DNA replication and together with BAZ1A/ACF1 is required for replication of pericentric heterochromatin in S-phase (PubMed:12434153). Probably plays a role in repression of RNA polymerase I dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter (By similarity). Essential component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex), a chromatin-remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure (PubMed:11980720, PubMed:15543136). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes (By similarity). Essential component of NoRC-5 ISWI chromatin-remodeling complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity)\n Location: Nucleus\n Domains: Helicase ATP-binding; Helicase C-terminal; SANT 1; SANT 2\n\nProtein 2: DAP3 (P51398, 398 AA)\n Function: As a component of the mitochondrial small ribosomal subunit, it plays a role in the translation of mitochondrial mRNAs (PubMed:39701103). Involved in mediating interferon-gamma-induced cell death (PubMed:7499268). Displays GTPase activity in vitro (PubMed:39701103)\n Location: Mitochondrion\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1209652, "gene_symbol_1": "SMARCA5", "gene_symbol_2": "DAP3", "detection_method": null, "compartment_type": "different", "uniprot_1": "O60264", "uniprot_2": "P51398"}} +{"question_id": "PPIL3-0087", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: VCP (P55072, 806 AA)\n Function: Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Involved in clearance process by mediating G3BP1 extraction from stress granules (PubMed:29804830, PubMed:34739333). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042605, PubMed:23042607). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (PubMed:35013556). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622, PubMed:38762759). Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333)\n Location: Cytoplasm, cytosol\n Domains: None\n\nProtein 2: STAT5A (P42229, 794 AA)\n Function: Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation\n Location: Cytoplasm\n Domains: SH2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 710970, "gene_symbol_1": "VCP", "gene_symbol_2": "STAT5A", "detection_method": null, "compartment_type": "same", "uniprot_1": "P55072", "uniprot_2": "P42229"}} +{"question_id": "PPIL3-0088", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NXF3 (Q9H4D5, 531 AA)\n Function: May function as a tissue-specific nuclear mRNA export factor\n Location: Nucleus\n Domains: NTF2; RRM\n\nProtein 2: ATP5MGL (Q7Z4Y8, 100 AA)\n Function: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane (By similarity)\n Location: Mitochondrion membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 989429, "gene_symbol_1": "NXF3", "gene_symbol_2": "ATP5MGL", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9H4D5", "uniprot_2": "Q7Z4Y8"}} +{"question_id": "PPIL3-0089", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ZWINT (O95229, 277 AA)\n Function: Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15094189, PubMed:15485811, PubMed:15824131, PubMed:16732327, PubMed:24530301, PubMed:27881301, PubMed:38459127, PubMed:38459128). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:15094189, PubMed:15485811, PubMed:16732327). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:15094189, PubMed:15485811, PubMed:15824131, PubMed:16732327, PubMed:24530301, PubMed:38459127, PubMed:38459128). Targets the RZZ complex to the kinetochore at prometaphase (PubMed:15485811). Recruits MAD2L1 to the kinetochore, but is not required for BUB1B localization (By similarity). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (PubMed:15485811)\n Location: Nucleus\n Domains: None\n\nProtein 2: KAT5 (Q92993, 513 AA)\n Function: Catalytic subunit of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H2A and H4 (PubMed:12776177, PubMed:14966270, PubMed:15042092, PubMed:15121871, PubMed:15310756, PubMed:16387653, PubMed:19909775, PubMed:25865756, PubMed:27153538, PubMed:29174981, PubMed:29335245, PubMed:32822602, PubMed:33076429). Histone acetylation alters nucleosome-DNA interactions and promotes interaction of the modified histones with other proteins which positively regulate transcription (PubMed:12776177, PubMed:14966270, PubMed:15042092, PubMed:15121871, PubMed:15310756). The NuA4 histone acetyltransferase complex is required for the activation of transcriptional programs associated with proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:17709392, PubMed:19783983, PubMed:32832608). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR): the complex inhibits TP53BP1 binding to chromatin via MBTD1, which recognizes and binds histone H4 trimethylated at 'Lys-20' (H4K20me), and KAT5 that catalyzes acetylation of 'Lys-15' of histone H2A (H2AK15ac), thereby blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks (PubMed:27153538, PubMed:32832608). Also involved in DSB repair by mediating acetylation of 'Lys-5' of histone H2AX (H2AXK5ac), promoting NBN/NBS1 assembly at the sites of DNA damage (PubMed:17709392, PubMed:26438602). The NuA4 complex plays a key role in hematopoietic stem cell maintenance and is required to maintain acetylated H2A.Z/H2AZ1 at MYC target genes (By similarity). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone hyperacetylation is required for histone replacement during the transition from round to elongating spermatids (By similarity). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Also acetylates non-histone proteins, such as BMAL1, ATM, AURKB, CHKA, CGAS, ERCC4/XPF, LPIN1, TP53/p53, NDC80/HEC1, NR1D2, RAN, SOX4, FOXP3, SQSTM1, ULK1 and RUBCNL/Pacer (PubMed:16141325, PubMed:17189187, PubMed:17360565, PubMed:17996965, PubMed:24835996, PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:30704899, PubMed:31857589, PubMed:32034146, PubMed:32817552, PubMed:34077757). Directly acetylates and activates ATM (PubMed:16141325). Promotes nucleotide excision repair (NER) by mediating acetylation of ERCC4/XPF, thereby promoting formation of the ERCC4-ERCC1 complex (PubMed:32034146). Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2 (PubMed:17996965). Acts as a regulator of regulatory T-cells (Treg) by catalyzing FOXP3 acetylation, thereby promoting FOXP3 transcriptional repressor activity (PubMed:17360565, PubMed:24835996). Involved in skeletal myoblast differentiation by mediating acetylation of SOX4 (PubMed:26291311). Catalyzes acetylation of APBB1/FE65, increasing its transcription activator activity (PubMed:33938178). Promotes transcription elongation during the activation phase of the circadian cycle by catalyzing acetylation of BMAL1, promoting elongation of circadian transcripts (By similarity). Together with GSK3 (GSK3A or GSK3B), acts as a regulator of autophagy: phosphorylated at Ser-86 by GSK3 under starvation conditions, leading to activate acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Acts as a regulator of the cGAS-STING innate antiviral response by catalyzing acetylation the N-terminus of CGAS, thereby promoting CGAS DNA-binding and activation (PubMed:32817552). Also regulates lipid metabolism by mediating acetylation of CHKA or LPIN1 (PubMed:34077757). Promotes lipolysis of lipid droplets following glucose deprivation by mediating acetylation of isoform 1 of CHKA, thereby promoting monomerization of CHKA and its conversion into a tyrosine-protein kinase (PubMed:34077757). Acts as a regulator of fatty-acid-induced triacylglycerol synthesis by catalyzing acetylation of LPIN1, thereby promoting the synthesis of diacylglycerol (PubMed:29765047). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), S-lactoyl-CoA (lactyl-CoA) and 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), and is able to mediate protein crotonylation, lactylation and 2-hydroxyisobutyrylation, respectively (PubMed:29192674, PubMed:34608293, PubMed:38961290). Acts as a key regulator of chromosome segregation and kinetochore-microtubule attachment during mitosis by mediating acetylation or crotonylation of target proteins (PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:34608293). Catalyzes acetylation of AURKB at kinetochores, increasing AURKB activity and promoting accurate chromosome segregation in mitosis (PubMed:26829474). Acetylates RAN during mitosis, promoting microtubule assembly at mitotic chromosomes (PubMed:29040603). Acetylates NDC80/HEC1 during mitosis, promoting robust kinetochore-microtubule attachment (PubMed:30409912). Catalyzes crotonylation of MAPRE1/EB1, thereby ensuring accurate spindle positioning in mitosis (PubMed:34608293). Catalyzes lactylation of NBN/NBS1 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290)\n Location: Nucleus\n Domains: MYST-type HAT; Tudor-knot\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 888652, "gene_symbol_1": "ZWINT", "gene_symbol_2": "KAT5", "detection_method": null, "compartment_type": "same", "uniprot_1": "O95229", "uniprot_2": "Q92993"}} +{"question_id": "PPIL3-0090", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CD3G (P09693, 182 AA)\n Function: Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G\n Location: Cell membrane\n Domains: ITAM; Ig-like\n\nProtein 2: MAGT1 (Q9H0U3, 335 AA)\n Function: Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains (PubMed:31831667). Involved in N-glycosylation of STT3B-dependent substrates (PubMed:31831667). Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with TUSC3. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Also has oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition. Could indirectly play a role in Mg(2+) transport in epithelial cells (Probable)\n Location: Cell membrane\n Domains: Thioredoxin\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 758895, "gene_symbol_1": "CD3G", "gene_symbol_2": "MAGT1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P09693", "uniprot_2": "Q9H0U3"}} +{"question_id": "PPIL3-0091", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SNRPE (P62304, 92 AA)\n Function: Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23246290, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:28781166). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077). As part of the U7 snRNP it is involved in histone 3'-end processing (PubMed:12975319)\n Location: Cytoplasm, cytosol\n Domains: Sm\n\nProtein 2: TLN1 (Q9Y490, 2541 AA)\n Function: High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane. With KANK1 co-organize the assembly of cortical microtubule stabilizing complexes (CMSCs) positioned to control microtubule-actin crosstalk at focal adhesions (FAs) rims\n Location: Cell projection, ruffle membrane\n Domains: FERM; I/LWEQ\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1257908, "gene_symbol_1": "SNRPE", "gene_symbol_2": "TLN1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P62304", "uniprot_2": "Q9Y490"}} +{"question_id": "PPIL3-0092", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NABP1 (Q96AH0, 204 AA)\n Function: Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways\n Location: Nucleus\n Domains: None\n\nProtein 2: SCNN1D (P51172, 802 AA)\n Function: Potential alternative pore-forming subunit of the epithelial sodium channel (ENaC), capable of replacing the alpha/SCNN1A subunit, creating a more active channel with distinct properties (PubMed:16423824, PubMed:19520916, PubMed:22505667). ENaC functions in epithelial tissues, where it facilitates the electrodiffusion of sodium ions from the extracellular fluid through the apical membrane of cells, with water following osmotically, regulating sodium balance and fluid homeostasis (PubMed:16423824, PubMed:19520916, PubMed:7499195). This subunit could also function independently as a sodium channel or assemble into other tissue-specific heterotrimeric sodium channels (PubMed:7499195)\n Location: Apical cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 878875, "gene_symbol_1": "NABP1", "gene_symbol_2": "SCNN1D", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q96AH0", "uniprot_2": "P51172"}} +{"question_id": "PPIL3-0093", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ARID4B (Q4LE39, 1312 AA)\n Function: Acts as a transcriptional repressor (PubMed:12724404). May function in the assembly and/or enzymatic activity of the Sin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes (PubMed:12724404). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4A. Involved in spermatogenesis, together with ARID4A, where it functions as a transcriptional coactivator for AR (androgen receptor) and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier. Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity)\n Location: Nucleus\n Domains: ARID; Tudor-knot\n\nProtein 2: ARID1A (O14497, 2285 AA)\n Function: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity)\n Location: Nucleus\n Domains: ARID\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 900301, "gene_symbol_1": "ARID4B", "gene_symbol_2": "ARID1A", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q4LE39", "uniprot_2": "O14497"}} +{"question_id": "PPIL3-0094", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NFRKB (Q6P4R8, 1299 AA)\n Function: Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'\n Location: Nucleus\n Domains: DEUBAD\n\nProtein 2: NR1I2 (O75469, 434 AA)\n Function: Nuclear receptor that acts as a transcription factor regulating genes involved in the metabolism and excretion of xenobiotics, drugs, and endogenous compounds. Activated by a broad range of endogenous steroids (e.g. pregnenolone, progesterone) and xenobiotics, including the antibiotic rifampicin and certain plant-derived metabolites. Upon ligand binding, translocates to the nucleus, forms a heterodimer with the retinoid X receptor/RXR, and binds to response elements in target promoters, leading to transcriptional activation. Target genes include cytochrome P450 enzymes such as CYP3A4 and ATP-binding cassette transporters including ABCB1/MDR1\n Location: Nucleus\n Domains: NR LBD\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 743691, "gene_symbol_1": "NFRKB", "gene_symbol_2": "NR1I2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q6P4R8", "uniprot_2": "O75469"}} +{"question_id": "PPIL3-0095", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: EMC6 (Q9BV81, 110 AA)\n Function: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:29242231, PubMed:29809151, PubMed:30415835, PubMed:32439656, PubMed:32459176). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:29242231, PubMed:29809151, PubMed:30415835). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:29809151, PubMed:30415835). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29242231, PubMed:29809151). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nProtein 2: CHUK (O15111, 745 AA)\n Function: Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973)\n Location: Cytoplasm\n Domains: Protein kinase\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1380044, "gene_symbol_1": "EMC6", "gene_symbol_2": "CHUK", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9BV81", "uniprot_2": "O15111"}} +{"question_id": "PPIL3-0096", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NFYC (Q13952, 458 AA)\n Function: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors\n Location: Nucleus\n Domains: None\n\nProtein 2: KATNB1 (Q9BVA0, 655 AA)\n Function: Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 659470, "gene_symbol_1": "NFYC", "gene_symbol_2": "KATNB1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q13952", "uniprot_2": "Q9BVA0"}} +{"question_id": "PPIL3-0097", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: EFNA5 (P52803, 228 AA)\n Function: Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion\n Location: Cell membrane\n Domains: Ephrin RBD\n\nProtein 2: SLC7A11 (Q9UPY5, 501 AA)\n Function: Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847, PubMed:11417227, PubMed:14722095, PubMed:15151999, PubMed:34880232, PubMed:35245456, PubMed:35352032). Provides L-cystine for the maintenance of the redox balance between extracellular L-cystine and L-cysteine and for the maintenance of the intracellular levels of glutathione that is essential for cells protection from oxidative stress (By similarity). The transport is sodium-independent, electroneutral with a stoichiometry of 1:1, and is drove by the high intracellular concentration of L-glutamate and the intracellular reduction of L-cystine (PubMed:11133847, PubMed:11417227). Acts as an inhibitor of ferroptosis by mediating the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis (PubMed:35245456, PubMed:40246981). Also inhibits ferroptosis by acting as an atypical proton transporter that mediates a slow proton efflux from lysosomes via cystine and glutamate flux (PubMed:40280132). Glutamate and cystine contain side-chain groups that are protonatable in the physiological range of lysosomal pH and cytosolic pH, respectively, enabling a slow lysosomal proton leak through a substrate-as-proton mechanism (PubMed:40280132). Moreover, mediates N-acetyl-L-cysteine uptake into the placenta leading to subsequently down-regulation of pathways associated with oxidative stress, inflammation and apoptosis (PubMed:34120018). In vitro can also transport L-aspartate (PubMed:11417227). May participate in astrocyte and meningeal cell proliferation during development and can provide neuroprotection by promoting glutathione synthesis and delivery from non-neuronal cells such as astrocytes and meningeal cells to immature neurons (By similarity). Controls the production of pheomelanin pigment directly (By similarity)\n Location: Cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 238609, "gene_symbol_1": "EFNA5", "gene_symbol_2": "SLC7A11", "detection_method": null, "compartment_type": "same", "uniprot_1": "P52803", "uniprot_2": "Q9UPY5"}} +{"question_id": "PPIL3-0098", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATP8A1 (Q9Y2Q0, 1164 AA)\n Function: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:31416931). Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules. In vitro, its ATPase activity is selectively and stereospecifically stimulated by phosphatidylserine (PS) (PubMed:31416931). The flippase complex ATP8A1:TMEM30A seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the cell membrane (By similarity). Acts as aminophospholipid translocase at the cell membrane in neuronal cells (By similarity)\n Location: Cytoplasmic vesicle, secretory vesicle, chromaffin granule membrane\n Domains: None\n\nProtein 2: OSBP (P22059, 807 AA)\n Function: Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol (cholesterol) with phosphatidylinositol 4-phosphate (PI4P, 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate)), delivering sterol to the Golgi in exchange for PI4P, which is subsequently degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum (PubMed:24209621, PubMed:28978670). Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol (PubMed:15746430, PubMed:17428193). Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly (PubMed:15746430). Regulates cholesterol efflux by decreasing the stability of the relatively short lived ABCA1 protein (an important point of control for cholesterol efflux activity) (PubMed:18450749)\n Location: Cytoplasm, cytosol\n Domains: PH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1639279, "gene_symbol_1": "ATP8A1", "gene_symbol_2": "OSBP", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9Y2Q0", "uniprot_2": "P22059"}} +{"question_id": "PPIL3-0099", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CTC1 (Q2NKJ3, 1217 AA)\n Function: Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity)\n Location: Nucleus\n Domains: None\n\nProtein 2: NRXN1 (P58400, 472 AA)\n Function: Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins (By similarity). Plays a role in formation of synaptic junctions (By similarity). Functions as part of a trans-synaptic complex by binding to cerebellins and postsynaptic GRID1. This interaction helps regulate the activity of NMDA and AMPA receptors at hippocampal synapses without affecting synapse formation. NRXN1B-CBLN2-GRID1 complex transduce presynaptic signals into postsynaptic NMDAR response (By similarity)\n Location: Presynaptic cell membrane\n Domains: Laminin G-like\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 676485, "gene_symbol_1": "CTC1", "gene_symbol_2": "NRXN1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q2NKJ3", "uniprot_2": "P58400"}} +{"question_id": "PPIL3-0100", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SNRNP200 (O75643, 2136 AA)\n Function: Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome (PubMed:35241646). Plays a role in pre-mRNA splicing as a core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154, PubMed:30728453). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome\n Location: Nucleus\n Domains: Helicase ATP-binding 1; Helicase ATP-binding 2; Helicase C-terminal 1; Helicase C-terminal 2; SEC63 1; SEC63 2\n\nProtein 2: YEATS4 (O95619, 227 AA)\n Function: Chromatin reader component of the NuA4 histone acetyltransferase (HAT) complex, a complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:12963728, PubMed:14966270). Specifically recognizes and binds acylated histone H3, with a preference for histone H3 diacetylated at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac) or histone H3 diacetylated at 'Lys-14' and 'Lys-27' (H3K14ac and H3K27ac) (PubMed:29437725, PubMed:29900004, PubMed:30071723). Also able to recognize and bind crotonylated histone H3 (PubMed:30071723). May also recognize and bind histone H3 succinylated at 'Lys-122' (H3K122succ); additional evidences are however required to confirm this result in vivo (PubMed:29463709). Plays a key role in histone variant H2AZ1/H2A.Z deposition into specific chromatin regions: recognizes and binds H3K14ac and H3K27ac on the promoters of actively transcribed genes and recruits NuA4-related complex to deposit H2AZ1/H2A.Z (PubMed:29437725). H2AZ1/H2A.Z deposition is required for maintenance of embryonic stem cell (By similarity)\n Location: Nucleus\n Domains: YEATS\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1573346, "gene_symbol_1": "SNRNP200", "gene_symbol_2": "YEATS4", "detection_method": null, "compartment_type": "same", "uniprot_1": "O75643", "uniprot_2": "O95619"}} +{"question_id": "PPIL3-0101", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BRCA2 (P51587, 3418 AA)\n Function: Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180)\n Location: Nucleus\n Domains: None\n\nProtein 2: ALYREF (Q86V81, 257 AA)\n Function: Functions as an mRNA export adapter; component of the transcription/export (TREX) complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602). Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B (PubMed:17984224). Plays a key role in mRNP recognition and mRNA packaging by bridging the mRNP-bound EJC and the TREX core complex (PubMed:37020021). TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1 (PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:37020021). Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC) (PubMed:15998806, PubMed:17984224, PubMed:37020021). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway) (PubMed:11675789, PubMed:11707413, PubMed:11979277, PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:18364396, PubMed:22144908, PubMed:22893130, PubMed:23222130, PubMed:25662211). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim (PubMed:19165146). Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling (PubMed:28418038). Acts as a chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation (PubMed:10488337). Involved in transcription elongation and genome stability (PubMed:12438613)\n Location: Nucleus\n Domains: RRM\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 900796, "gene_symbol_1": "BRCA2", "gene_symbol_2": "ALYREF", "detection_method": null, "compartment_type": "same", "uniprot_1": "P51587", "uniprot_2": "Q86V81"}} +{"question_id": "PPIL3-0102", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SPTLC1 (O15269, 473 AA)\n Function: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nProtein 2: EPRS1 (P07814, 1512 AA)\n Function: Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (PubMed:23263184, PubMed:24100331, PubMed:29576217, PubMed:3290852, PubMed:37212275). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3'-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts (PubMed:15479637, PubMed:23071094). Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239)\n Location: Cytoplasm, cytosol\n Domains: WHEP-TRS 1; WHEP-TRS 2; WHEP-TRS 3\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1403814, "gene_symbol_1": "SPTLC1", "gene_symbol_2": "EPRS1", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15269", "uniprot_2": "P07814"}} +{"question_id": "PPIL3-0103", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TIMM23 (O14925, 209 AA)\n Function: Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane (PubMed:10339406). Has a role in the activation of stress-induced mitophagy by protecting PINK1 from OMA1-mediated degradation and facilitating its accumulation at the outer mitochondrial membrane in response to depolarization (PubMed:37160114)\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: PER2 (O15055, 1255 AA)\n Function: Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndrome and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors. PER appears to regulate circadian control of transcription by at least three different modes. First, interacts directly with the CLOCK-BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription. Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1. The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases. Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-BMAL1 interactions. Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. May propagate clock information to metabolic pathways via the interaction with nuclear receptors. Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like BMAL1 or G6PC1. Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby inhibiting transcriptional activation. Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels. Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas. Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression. May also be involved in the regulation of inflammatory processes. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1\n Location: Nucleus\n Domains: PAC; PAS 1; PAS 2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 43865, "gene_symbol_1": "TIMM23", "gene_symbol_2": "PER2", "detection_method": null, "compartment_type": "different", "uniprot_1": "O14925", "uniprot_2": "O15055"}} +{"question_id": "PPIL3-0104", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: PPARG (P37231, 505 AA)\n Function: Ligand-activated transcription factor that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-oxidation of fatty acids (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Activated by lipid ligands: binds peroxisome proliferators, such as hypolipidemic drugs, and fatty acids, such as prostaglandin J2 metabolites (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Ligand-binding results in a conformational change in the receptor, promoting dissociation of repressors and recruitment of coactivators, and subsequent activation of target gene expression (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Specifically binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase (By similarity). Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses (PubMed:20829347). Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)\n Location: Nucleus\n Domains: NR LBD\n\nProtein 2: PNPT1 (Q8TCS8, 783 AA)\n Function: RNA-binding protein implicated in numerous RNA metabolic processes (PubMed:29967381, PubMed:39019044). Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction (PubMed:29967381, PubMed:39019044). Mitochondrial intermembrane factor with RNA-processing exoribonulease activity (PubMed:29967381, PubMed:39019044). Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner (PubMed:29967381, PubMed:39019044). Involved in the degradation of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules (PubMed:29967381, PubMed:39019044). Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Also plays a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA\n Location: Cytoplasm\n Domains: KH; S1 motif\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1085116, "gene_symbol_1": "PPARG", "gene_symbol_2": "PNPT1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P37231", "uniprot_2": "Q8TCS8"}} +{"question_id": "PPIL3-0105", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: HGS (O14964, 777 AA)\n Function: Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation\n Location: Cytoplasm\n Domains: UIM; VHS\n\nProtein 2: CCNA1 (P78396, 465 AA)\n Function: May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1254676, "gene_symbol_1": "HGS", "gene_symbol_2": "CCNA1", "detection_method": null, "compartment_type": "different", "uniprot_1": "O14964", "uniprot_2": "P78396"}} +{"question_id": "PPIL3-0106", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: POP7 (O75817, 140 AA)\n Function: Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:30454648, PubMed:9630247). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465)\n Location: Nucleus, nucleolus\n Domains: None\n\nProtein 2: BAZ1A (Q9NRL2, 1556 AA)\n Function: Regulatory subunit of the ATP-dependent ACF-1 and ACF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and slide edge- and center-positioned histone octamers away from their original location on the DNA template to facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:17099699, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner (PubMed:14759371, PubMed:17099699, PubMed:28801535). The ACF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the ACF-5 ISWI chromatin remodeling complex (PubMed:28801535). Has a role in sensing the length of DNA which flank nucleosomes, which modulates the nucleosome spacing activity of the ACF-5 ISWI chromatin remodeling complex (PubMed:17099699). Involved in DNA replication and together with SMARCA5/SNF2H is required for replication of pericentric heterochromatin in S-phase (PubMed:12434153). May have a role in nuclear receptor-mediated transcription repression (PubMed:17519354)\n Location: Nucleus\n Domains: Bromo; DDT; WAC\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1137079, "gene_symbol_1": "POP7", "gene_symbol_2": "BAZ1A", "detection_method": null, "compartment_type": "same", "uniprot_1": "O75817", "uniprot_2": "Q9NRL2"}} +{"question_id": "PPIL3-0107", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATP6V1F (Q16864, 119 AA)\n Function: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity)\n Location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane\n Domains: None\n\nProtein 2: CEP152 (O94986, 1710 AA)\n Function: Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). Acts as a molecular scaffold facilitating the interaction of PLK4 and CPAP, 2 molecules involved in centriole formation (PubMed:20852615, PubMed:21059844). Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure (PubMed:24997597). Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (By similarity). Overexpression of CEP152 can drive amplification of centrioles (PubMed:20852615)\n Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 705725, "gene_symbol_1": "ATP6V1F", "gene_symbol_2": "CEP152", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q16864", "uniprot_2": "O94986"}} +{"question_id": "PPIL3-0108", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: H2BC15 (Q99877, 126 AA)\n Function: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling\n Location: Nucleus\n Domains: None\n\nProtein 2: DAPP1 (Q9UN19, 280 AA)\n Function: May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K\n Location: Cytoplasm\n Domains: PH; SH2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 473272, "gene_symbol_1": "H2BC15", "gene_symbol_2": "DAPP1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q99877", "uniprot_2": "Q9UN19"}} +{"question_id": "PPIL3-0109", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NR1H2 (P55055, 460 AA)\n Function: Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (By similarity). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957)\n Location: Nucleus\n Domains: NR LBD\n\nProtein 2: SMAD3 (P84022, 425 AA)\n Function: Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator\n Location: Cytoplasm\n Domains: MH1; MH2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 243843, "gene_symbol_1": "NR1H2", "gene_symbol_2": "SMAD3", "detection_method": null, "compartment_type": "different", "uniprot_1": "P55055", "uniprot_2": "P84022"}} +{"question_id": "PPIL3-0110", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ENY2 (Q9NPA8, 101 AA)\n Function: Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes. The transcription regulatory histone acetylation (HAT) complex SAGA is a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation (PubMed:18206972, PubMed:21746879). As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (PubMed:23591820)\n Location: Nucleus, nucleoplasm\n Domains: None\n\nProtein 2: PRKCSH (P14314, 528 AA)\n Function: Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity)\n Location: Endoplasmic reticulum\n Domains: EF-hand 1; EF-hand 2; LDL-receptor class A 1; LDL-receptor class A 2; MRH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 989172, "gene_symbol_1": "ENY2", "gene_symbol_2": "PRKCSH", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9NPA8", "uniprot_2": "P14314"}} +{"question_id": "PPIL3-0111", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: GET3 (O43681, 348 AA)\n Function: ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (PubMed:17382883). Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1/WRB and CAMLG/GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-CAMLG receptor, and returning it to the cytosol to initiate a new round of targeting. May be involved in insulin signaling\n Location: Cytoplasm\n Domains: None\n\nProtein 2: HCFC1 (P51610, 2035 AA)\n Function: Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity)\n Location: Cytoplasm\n Domains: Fibronectin type-III 1; Fibronectin type-III 2; Fibronectin type-III 3\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 773834, "gene_symbol_1": "GET3", "gene_symbol_2": "HCFC1", "detection_method": null, "compartment_type": "same", "uniprot_1": "O43681", "uniprot_2": "P51610"}} +{"question_id": "PPIL3-0112", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: HAUS6 (Q7Z4H7, 955 AA)\n Function: Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin\n Location: Cytoplasm, cytoskeleton\n Domains: None\n\nProtein 2: THUMPD2 (Q9BTF0, 503 AA)\n Function: Catalytic subunit of the THUMPD2-TRM112 methyltransferase complex, that specifically mediates the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotides, most probably at position 72 (m2G72), in the U6snRNA of the major spliceosome (PubMed:37283053). This modification in the U6 snRNA affects the constitutive splicing efficiency of introns that have suboptimal splice sites and can impact final mRNA levels (PubMed:37283053)\n Location: Nucleus\n Domains: THUMP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1025956, "gene_symbol_1": "HAUS6", "gene_symbol_2": "THUMPD2", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q7Z4H7", "uniprot_2": "Q9BTF0"}} +{"question_id": "PPIL3-0113", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TCAP (O15273, 167 AA)\n Function: Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk\n Location: Cytoplasm, myofibril, sarcomere\n Domains: None\n\nProtein 2: VDR (P11473, 427 AA)\n Function: Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:10678179, PubMed:15728261, PubMed:16913708, PubMed:28698609, PubMed:37478846). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638)\n Location: Nucleus\n Domains: NR LBD\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1052293, "gene_symbol_1": "TCAP", "gene_symbol_2": "VDR", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15273", "uniprot_2": "P11473"}} +{"question_id": "PPIL3-0114", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATP6V1H (Q9UI12, 483 AA)\n Function: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Subunit H is essential for V-ATPase activity, but not for the assembly of the complex (By similarity). Involved in the endocytosis mediated by clathrin-coated pits, required for the formation of endosomes (PubMed:12032142)\n Location: Cytoplasmic vesicle, clathrin-coated vesicle membrane\n Domains: None\n\nProtein 2: PIGA (P37287, 484 AA)\n Function: Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis\n Location: Rough endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 964322, "gene_symbol_1": "ATP6V1H", "gene_symbol_2": "PIGA", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9UI12", "uniprot_2": "P37287"}} +{"question_id": "PPIL3-0115", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MTREX (P42285, 1042 AA)\n Function: Catalyzes the ATP-dependent unwinding of RNA duplexes with a single-stranded 3' RNA extension (PubMed:27871484, PubMed:29844170, PubMed:29906447). Central subunit of many protein complexes, namely TRAMP-like, nuclear exosome targeting (NEXT) and poly(A) tail exosome targeting (PAXT) (PubMed:21855801, PubMed:27871484, PubMed:29844170). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484, PubMed:29844170). PAXT directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor ZCCHC8, which links to RNA-binding protein adapters (PubMed:27871484). Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA (PubMed:17412707, PubMed:29107693). May be involved in pre-mRNA splicing. In the context of NEXT complex can also in vitro unwind DNA:RNA heteroduplexes with a 3' poly (A) RNA tracking strand (PubMed:29844170). Can promote unwinding and degradation of structured RNA substrates when associated with the nuclear exosome and its cofactors. Can displace a DNA strand while translocating on RNA to ultimately degrade the RNA within a DNA/RNA heteroduplex (PubMed:29906447). Plays a role in DNA damage response (PubMed:29902117)\n Location: Nucleus, nucleoplasm\n Domains: Helicase ATP-binding; Helicase C-terminal\n\nProtein 2: PDHA1 (P08559, 390 AA)\n Function: Together with PDHB forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex (PubMed:17474719, PubMed:19081061). The PDH complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle (PubMed:19081061, PubMed:7782287). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3) (Probable). The E1 subunit catalyzes both the thiamine pyrophosphate (TPP)-dependent decarboxylation of pyruvate and the reductive acetylation of a lipoyl group covalently linked to the lipoyl-bearing domains of E2 (PubMed:17474719, PubMed:19081061, PubMed:7782287)\n Location: Mitochondrion matrix\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 696375, "gene_symbol_1": "MTREX", "gene_symbol_2": "PDHA1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P42285", "uniprot_2": "P08559"}} +{"question_id": "PPIL3-0116", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: HNF4G (Q14541, 408 AA)\n Function: Transcription factor. Has a lower transcription activation potential than HNF4-alpha\n Location: Nucleus\n Domains: NR LBD\n\nProtein 2: RPRD1A (Q96P16, 312 AA)\n Function: Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle\n Location: Nucleus\n Domains: CID\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 307499, "gene_symbol_1": "HNF4G", "gene_symbol_2": "RPRD1A", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q14541", "uniprot_2": "Q96P16"}} +{"question_id": "PPIL3-0117", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: INTS3 (Q68E01, 1043 AA)\n Function: Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144). Within the integrator complex, INTS3 is involved in the post-termination step: INTS3 binds INTS7 in the open conformation of integrator complex and prevents the rebinding of Pol II to the integrator after termination cycle (PubMed:38570683). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267)\n Location: Nucleus\n Domains: None\n\nProtein 2: ACTR8 (Q9H981, 624 AA)\n Function: Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 869626, "gene_symbol_1": "INTS3", "gene_symbol_2": "ACTR8", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q68E01", "uniprot_2": "Q9H981"}} +{"question_id": "PPIL3-0118", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: HYKK (A2RU49, 373 AA)\n Function: Catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine\n Location: Cytoplasm\n Domains: None\n\nProtein 2: PBX3 (P40426, 434 AA)\n Function: Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'\n Location: Nucleus\n Domains: PBC\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 9994, "gene_symbol_1": "HYKK", "gene_symbol_2": "PBX3", "detection_method": null, "compartment_type": "different", "uniprot_1": "A2RU49", "uniprot_2": "P40426"}} +{"question_id": "PPIL3-0119", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CAMK1 (Q14012, 370 AA)\n Function: Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I\n Location: Cytoplasm\n Domains: Protein kinase\n\nProtein 2: SPMIP6 (Q8NCR6, 262 AA)\n Function: May participate in intramanchette transport and midpiece formation of the sperm tail. May play a potential role in somatic cell proliferation\n Location: Cytoplasm, cytoskeleton\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 302657, "gene_symbol_1": "CAMK1", "gene_symbol_2": "SPMIP6", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q14012", "uniprot_2": "Q8NCR6"}} +{"question_id": "PPIL3-0120", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: VPS18 (Q9P253, 973 AA)\n Function: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in dendrite development of Pukinje cells (By similarity)\n Location: Late endosome membrane\n Domains: None\n\nProtein 2: SDC1 (P18827, 310 AA)\n Function: Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413). Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (By similarity)\n Location: Membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 675022, "gene_symbol_1": "VPS18", "gene_symbol_2": "SDC1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9P253", "uniprot_2": "P18827"}} +{"question_id": "PPIL3-0121", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATF2 (P15336, 505 AA)\n Function: Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro (PubMed:10821277). In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type\n Location: Nucleus\n Domains: bZIP\n\nProtein 2: EXOC6 (Q8TAG9, 804 AA)\n Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. Together with RAB11A, RAB3IP, RAB8A, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (By similarity)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 708953, "gene_symbol_1": "ATF2", "gene_symbol_2": "EXOC6", "detection_method": null, "compartment_type": "different", "uniprot_1": "P15336", "uniprot_2": "Q8TAG9"}} +{"question_id": "PPIL3-0122", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ANOS1 (P23352, 680 AA)\n Function: Has a dual branch-promoting and guidance activity, which may play an important role in the patterning of mitral and tufted cell collaterals to the olfactory cortex (By similarity). Chemoattractant for fetal olfactory epithelial cells\n Location: Cell membrane\n Domains: Fibronectin type-III 1; Fibronectin type-III 2; Fibronectin type-III 3; Fibronectin type-III 4; WAP\n\nProtein 2: ZBTB4 (Q9P1Z0, 1013 AA)\n Function: Transcriptional repressor with bimodal DNA-binding specificity. Represses transcription in a methyl-CpG-dependent manner. Binds with a higher affinity to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' but can also bind to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Can also bind specifically to a single methyl-CpG pair and can bind hemimethylated DNA but with a lower affinity compared to methylated DNA (PubMed:16354688). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (By similarity)\n Location: Nucleus\n Domains: BTB\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 184605, "gene_symbol_1": "ANOS1", "gene_symbol_2": "ZBTB4", "detection_method": null, "compartment_type": "different", "uniprot_1": "P23352", "uniprot_2": "Q9P1Z0"}} +{"question_id": "PPIL3-0123", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATP5PF (P18859, 108 AA)\n Function: Subunit F6, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). Part of the complex F(0) domain (PubMed:37244256). Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements (By similarity)\n Location: Mitochondrion\n Domains: None\n\nProtein 2: RPA4 (Q13156, 261 AA)\n Function: As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1008953, "gene_symbol_1": "ATP5PF", "gene_symbol_2": "RPA4", "detection_method": null, "compartment_type": "different", "uniprot_1": "P18859", "uniprot_2": "Q13156"}} +{"question_id": "PPIL3-0124", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MPHOSPH10 (O00566, 681 AA)\n Function: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing (PubMed:12655004). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797)\n Location: Nucleus, nucleolus\n Domains: None\n\nProtein 2: USF2 (Q15853, 346 AA)\n Function: Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters\n Location: Nucleus\n Domains: bHLH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1636362, "gene_symbol_1": "MPHOSPH10", "gene_symbol_2": "USF2", "detection_method": null, "compartment_type": "same", "uniprot_1": "O00566", "uniprot_2": "Q15853"}} +{"question_id": "PPIL3-0125", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ITGAM (P11215, 1152 AA)\n Function: Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (PubMed:20008295, PubMed:9558116). It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin ITGAM/ITGB2 is also a receptor for fibrinogen and factor X. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration (PubMed:28807980). In association with beta subunit ITGB2/CD18, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). Integrin ITGAM/ITGB2 is also a receptor for ICAM1 ligand ensuring adhesion between stimulated neutrophils and stimulated endothelial cells (PubMed:1980124). May regulate phagocytosis-induced apoptosis in extravasated neutrophils (By similarity). May play a role in mast cell development (By similarity). Required with TYROBP/DAP12 in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (By similarity)\n Location: Cell membrane\n Domains: VWFA\n\nProtein 2: SPCS1 (Q9Y6A9, 169 AA)\n Function: Component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (PubMed:34388369). Dispensable for SPC enzymatic activity (By similarity)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 629914, "gene_symbol_1": "ITGAM", "gene_symbol_2": "SPCS1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P11215", "uniprot_2": "Q9Y6A9"}} +{"question_id": "PPIL3-0126", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SGF29 (Q96ES7, 293 AA)\n Function: Chromatin reader component of some histone acetyltransferase (HAT) SAGA-type complexes like the TFTC-HAT, ATAC or STAGA complexes (PubMed:19103755, PubMed:20850016, PubMed:21685874, PubMed:26421618, PubMed:26578293). SGF29 specifically recognizes and binds methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3) (PubMed:20850016, PubMed:21685874, PubMed:26421618, PubMed:26578293). In the SAGA-type complexes, SGF29 is required to recruit complexes to H3K4me (PubMed:20850016). Involved in the response to endoplasmic reticulum (ER) stress by recruiting the SAGA complex to H3K4me, thereby promoting histone H3 acetylation and cell survival (PubMed:23894581). Also binds non-histone proteins that are methylated on Lys residues: specifically recognizes and binds CGAS monomethylated on 'Lys-506' (By similarity)\n Location: Nucleus\n Domains: SGF29 C-terminal\n\nProtein 2: JAK1 (P23458, 1154 AA)\n Function: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552)\n Location: Endomembrane system\n Domains: FERM; Protein kinase 1; Protein kinase 2; SH2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 568142, "gene_symbol_1": "SGF29", "gene_symbol_2": "JAK1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q96ES7", "uniprot_2": "P23458"}} +{"question_id": "PPIL3-0127", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: KCNE1 (P15382, 129 AA)\n Function: Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits. KCNE1 beta subunit modulates the gating kinetics and enhances stability of the channel complex (PubMed:19219384, PubMed:20533308, PubMed:9230439). Alters the gating of the delayed rectifier Kv channel containing KCNB1 alpha subunit (PubMed:19219384). Associates with KCNQ1/KVLQT1 alpha subunit to form the slowly activating delayed rectifier cardiac potassium (IKs) channel responsible for ventricular muscle action potential repolarization (PubMed:20533308). The outward current reaches its steady state only after 50 seconds (Probable). Assembly with KCNH2/HERG alpha subunit Kv channel may regulate the rapidly activating component of the delayed rectifying potassium current (IKr) in heart (PubMed:9230439)\n Location: Cell membrane\n Domains: None\n\nProtein 2: THOC6 (Q86W42, 341 AA)\n Function: Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Plays a key structural role in the oligomerization of the THO-DDX39B complex (PubMed:33191911). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15998806, PubMed:17190602). Plays a role in apoptosis negative control involved in brain development (PubMed:15833825, PubMed:23621916)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 642197, "gene_symbol_1": "KCNE1", "gene_symbol_2": "THOC6", "detection_method": null, "compartment_type": "different", "uniprot_1": "P15382", "uniprot_2": "Q86W42"}} +{"question_id": "PPIL3-0128", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RRM2B (Q7LG56, 351 AA)\n Function: Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage\n Location: Cytoplasm\n Domains: None\n\nProtein 2: EXOC8 (Q8IYI6, 725 AA)\n Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane\n Location: Cytoplasm\n Domains: PH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 693692, "gene_symbol_1": "RRM2B", "gene_symbol_2": "EXOC8", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q7LG56", "uniprot_2": "Q8IYI6"}} +{"question_id": "PPIL3-0129", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: COQ9 (O75208, 318 AA)\n Function: Membrane-associated protein that warps the membrane surface to access and bind aromatic isoprenes with high specificity, including ubiquinone (CoQ) isoprene intermediates and presents them directly to COQ7, therefore facilitating the COQ7-mediated hydroxylase step (PubMed:25339443, PubMed:30661980, PubMed:38425362). Participates in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:25339443, PubMed:30661980)\n Location: Mitochondrion\n Domains: None\n\nProtein 2: DBT (P11182, 482 AA)\n Function: The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component\n Location: Mitochondrion matrix\n Domains: Lipoyl-binding; Peripheral subunit-binding (PSBD)\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1626286, "gene_symbol_1": "COQ9", "gene_symbol_2": "DBT", "detection_method": null, "compartment_type": "same", "uniprot_1": "O75208", "uniprot_2": "P11182"}} +{"question_id": "PPIL3-0130", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: GORASP2 (Q9H8Y8, 452 AA)\n Function: Key structural protein of the Golgi apparatus (PubMed:33301566). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon (PubMed:33301566). Acting in concert with GORASP1/GRASP65, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks (PubMed:33301566). However, other studies suggest that GORASP2 plays a role in the assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after breakdown during mitosis and meiosis (PubMed:10487747, PubMed:21515684, PubMed:22523075). May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA (PubMed:11101516). Required for normal acrosome formation during spermiogenesis and normal male fertility, probably by promoting colocalization of JAM2 and JAM3 at contact sites between germ cells and Sertoli cells (By similarity). Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (PubMed:21884936, PubMed:27062250, PubMed:28067262)\n Location: Golgi apparatus membrane\n Domains: PDZ GRASP-type 1; PDZ GRASP-type 2\n\nProtein 2: MCM9 (Q9NXL9, 1143 AA)\n Function: Component of the MCM8-MCM9 complex, which is involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). The MCM8-MCM9 complex is a 3'-5' DNA helicase and single-stranded (ss)DNA-stimulated ATPase which binds ssDNA in the presence of nucleoside triphosphates (PubMed:37309874). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs, probably by regulating the localization of the MNR complex (PubMed:23401855). Acts as a helicase in DNA mismatch repair (MMR) following DNA replication errors to unwind the mismatch containing DNA strand (PubMed:26300262). In addition, recruits MLH1, a component of the MMR complex, to chromatin (PubMed:26300262). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). Plays a key role during gametogenesis, probably by regulating HR (By similarity)\n Location: Nucleus\n Domains: MCM C-terminal AAA(+) ATPase\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1042557, "gene_symbol_1": "GORASP2", "gene_symbol_2": "MCM9", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9H8Y8", "uniprot_2": "Q9NXL9"}} +{"question_id": "PPIL3-0131", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: PDP1 (Q9P0J1, 537 AA)\n Function: Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA\n Location: Mitochondrion\n Domains: PPM-type phosphatase\n\nProtein 2: COQ4 (Q9Y3A0, 265 AA)\n Function: Lyase that catalyzes the C1-decarboxylation of 4-hydroxy-3-methoxy-5-(all-trans-decaprenyl)benzoic acid into 2-methoxy-6-(all-trans-decaprenyl)phenol during ubiquinone biosynthesis\n Location: Mitochondrion inner membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1271454, "gene_symbol_1": "PDP1", "gene_symbol_2": "COQ4", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9P0J1", "uniprot_2": "Q9Y3A0"}} +{"question_id": "PPIL3-0132", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: GABRA6 (Q16445, 453 AA)\n Function: Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:8632757). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity). Alpha-6/GABRA6 subunits are found at both synaptic and extrasynaptic sites (PubMed:8632757). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). Extrasynaptic alpha-6-containing receptors contribute to the tonic GABAergic inhibition. Alpha-6 subunits are also present on glutamatergic synapses (By similarity)\n Location: Postsynaptic cell membrane\n Domains: None\n\nProtein 2: ATF6 (P18850, 670 AA)\n Function: Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane (PubMed:10564271, PubMed:11158310, PubMed:11779464). Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR) (PubMed:10564271, PubMed:11158310, PubMed:11779464)\n Location: Endoplasmic reticulum membrane\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1015757, "gene_symbol_1": "GABRA6", "gene_symbol_2": "ATF6", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q16445", "uniprot_2": "P18850"}} +{"question_id": "PPIL3-0133", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CASC3 (O15234, 703 AA)\n Function: Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homomer\n Location: Cytoplasm\n Domains: None\n\nProtein 2: PIGC (Q92535, 297 AA)\n Function: Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1034005, "gene_symbol_1": "CASC3", "gene_symbol_2": "PIGC", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15234", "uniprot_2": "Q92535"}} +{"question_id": "PPIL3-0134", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CCNK (O75909, 580 AA)\n Function: Regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases. Plays a role in transcriptional regulation via its role in regulating the phosphorylation of the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A)\n Location: Nucleus\n Domains: None\n\nProtein 2: DPY30 (Q9C005, 99 AA)\n Function: As part of the MLL1/MLL complex, involved in the methylation of histone H3 at 'Lys-4', particularly trimethylation. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In a teratocarcinoma cell, plays a crucial role in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci. May also play an indirect or direct role in endosomal transport\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 639204, "gene_symbol_1": "CCNK", "gene_symbol_2": "DPY30", "detection_method": null, "compartment_type": "same", "uniprot_1": "O75909", "uniprot_2": "Q9C005"}} +{"question_id": "PPIL3-0135", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: COX7A2 (P14406, 83 AA)\n Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: ATF7 (P17544, 483 AA)\n Function: Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation (PubMed:29490055). In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes (By similarity). Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation (By similarity). In response to TNF, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening (PubMed:29490055). Also plays a role in maintaining epithelial regenerative capacity and protecting against cell death during intestinal epithelial damage and repair (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1703286, "gene_symbol_1": "COX7A2", "gene_symbol_2": "ATF7", "detection_method": null, "compartment_type": "different", "uniprot_1": "P14406", "uniprot_2": "P17544"}} +{"question_id": "PPIL3-0136", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: HELLS (Q9NRZ9, 838 AA)\n Function: ATP-dependent chromatin remodeler that regulates chromatin accessibility, DNA methylation, and histone modifications. It facilitates de novo DNA methylation at repetitive sequences and promotes transcriptional silencing via recruitment of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), contributing to heterochromatin formation and repression of transposable elements (PubMed:30307408). Also involved in DNA repair by recruiting DNA damage response mediators to double-strand breaks in heterochromatin, promoting homologous recombination via RBBP8/CtIP-dependent end resection (PubMed:22946062, PubMed:31802118). During meiosis, it is recruited by PRDM9 to recombination hotspots, aiding chromatin opening (PubMed:32001511). Through these diverse roles, is crucial for processes such as development, differentiation, and genomic stability (PubMed:22946062, PubMed:31802118). Involved in regulation of the expansion or survival of lymphoid cells (By similarity)\n Location: Nucleus\n Domains: Helicase ATP-binding; Helicase C-terminal\n\nProtein 2: BARX2 (Q9UMQ3, 279 AA)\n Function: Transcription factor. Binds optimally to the DNA consensus sequence 5'-YYTAATGRTTTTY-3'. May control the expression of neural adhesion molecules such as L1 or Ng-CAM during embryonic development of both the central and peripherical nervous system. May be involved in controlling adhesive processes in keratinizing epithelia (By similarity)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 493473, "gene_symbol_1": "HELLS", "gene_symbol_2": "BARX2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9NRZ9", "uniprot_2": "Q9UMQ3"}} +{"question_id": "PPIL3-0137", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: IKBKE (Q14164, 716 AA)\n Function: Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1\n Location: Cytoplasm\n Domains: Protein kinase\n\nProtein 2: MCU (Q8NE86, 351 AA)\n Function: Channel-forming and calcium-conducting subunit of the mitochondrial inner membrane calcium uniporter complex (uniplex), which mediates calcium uptake into the mitochondrial matrix (PubMed:21685886, PubMed:21685888, PubMed:22822213, PubMed:22829870, PubMed:22904319, PubMed:23101630, PubMed:23178883, PubMed:23755363, PubMed:24332854, PubMed:24560927, PubMed:26341627, PubMed:29954988, PubMed:29995857, PubMed:30454562, PubMed:30638448, PubMed:31080062, PubMed:32494073, PubMed:32762847, PubMed:33296646, PubMed:37036971, PubMed:37126688). MCU channel activity is regulated by the calcium-sensor subunits of the uniplex MICU1 and MICU2 (or MICU3) (PubMed:24560927, PubMed:26903221, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32762847, PubMed:37036971, PubMed:37126688). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates ATP production, cytoplasmic calcium signals and activation of cell death pathways (PubMed:21685886, PubMed:21685888, PubMed:22822213, PubMed:22829870, PubMed:22904319, PubMed:23101630, PubMed:23178883, PubMed:23755363, PubMed:24332854, PubMed:24560927, PubMed:26341627, PubMed:29954988, PubMed:32494073, PubMed:32762847). Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (PubMed:22822213). While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells (PubMed:25603276). Participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22829870, PubMed:22904319). Involved in antigen processing and presentation (By similarity)\n Location: Mitochondrion inner membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 679575, "gene_symbol_1": "IKBKE", "gene_symbol_2": "MCU", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q14164", "uniprot_2": "Q8NE86"}} +{"question_id": "PPIL3-0138", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: APLF (Q8IW19, 511 AA)\n Function: Histone chaperone involved in single-strand and double-strand DNA break repair (PubMed:17353262, PubMed:17396150, PubMed:21211721, PubMed:21211722, PubMed:29905837, PubMed:30104678). Recruited to sites of DNA damage through interaction with branched poly-ADP-ribose chains, a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions (PubMed:17353262, PubMed:17396150, PubMed:21211721, PubMed:30104678). Following recruitment to DNA damage sites, acts as a histone chaperone that mediates histone eviction during DNA repair and promotes recruitment of histone variant MACROH2A1 (PubMed:21211722, PubMed:29905837, PubMed:30104678). Also has a nuclease activity: displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro (PubMed:17353262, PubMed:17396150). Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage (PubMed:17353262, PubMed:17396150). Together with PARP3, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721, PubMed:23689425). Also acts as a negative regulator of cell pluripotency by promoting histone exchange (By similarity). Required for the embryo implantation during the epithelial to mesenchymal transition in females (By similarity)\n Location: Nucleus\n Domains: FHA-like\n\nProtein 2: NFATC2IP (Q8NCF5, 419 AA)\n Function: In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity)\n Location: Nucleus\n Domains: Ubiquitin-like\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 404889, "gene_symbol_1": "APLF", "gene_symbol_2": "NFATC2IP", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q8IW19", "uniprot_2": "Q8NCF5"}} +{"question_id": "PPIL3-0139", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RFC5 (P40937, 340 AA)\n Function: Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA\n Location: Nucleus\n Domains: None\n\nProtein 2: BLOC1S4 (Q9NUP1, 217 AA)\n Function: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1066146, "gene_symbol_1": "RFC5", "gene_symbol_2": "BLOC1S4", "detection_method": null, "compartment_type": "different", "uniprot_1": "P40937", "uniprot_2": "Q9NUP1"}} +{"question_id": "PPIL3-0140", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CCNK (O75909, 580 AA)\n Function: Regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases. Plays a role in transcriptional regulation via its role in regulating the phosphorylation of the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A)\n Location: Nucleus\n Domains: None\n\nProtein 2: TANK (Q92844, 425 AA)\n Function: Adapter protein involved in I-kappa-B-kinase (IKK) regulation which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity. Acts as a regulator of TRAF function by maintaining them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. Negatively regulates NF-kappaB signaling and cell survival upon DNA damage (PubMed:25861989). Plays a role as an adapter to assemble ZC3H12A, USP10 in a deubiquitination complex which plays a negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Promotes UBP10-induced deubiquitination of TRAF6 in response to DNA damage (PubMed:25861989). May control negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1233341, "gene_symbol_1": "CCNK", "gene_symbol_2": "TANK", "detection_method": null, "compartment_type": "different", "uniprot_1": "O75909", "uniprot_2": "Q92844"}} +{"question_id": "PPIL3-0141", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CEBPA (P49715, 358 AA)\n Function: Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes (PubMed:11242107). During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (By similarity). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Down-regulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters. Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nProtein 2: EXOSC9 (Q06265, 439 AA)\n Function: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC9 binds to ARE-containing RNAs\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1197766, "gene_symbol_1": "CEBPA", "gene_symbol_2": "EXOSC9", "detection_method": null, "compartment_type": "different", "uniprot_1": "P49715", "uniprot_2": "Q06265"}} +{"question_id": "PPIL3-0142", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: GET4 (Q7L5D6, 327 AA)\n Function: As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892, PubMed:32395830). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:25535373, PubMed:28104892). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303)\n Location: Cytoplasm, cytosol\n Domains: None\n\nProtein 2: RICTOR (Q6R327, 1708 AA)\n Function: Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718)\n Location: Cell membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 946070, "gene_symbol_1": "GET4", "gene_symbol_2": "RICTOR", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q7L5D6", "uniprot_2": "Q6R327"}} +{"question_id": "PPIL3-0143", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RELA (Q04206, 551 AA)\n Function: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148)\n Location: Nucleus\n Domains: RHD\n\nProtein 2: CNOT9 (Q92600, 299 AA)\n Function: Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1575836, "gene_symbol_1": "RELA", "gene_symbol_2": "CNOT9", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q04206", "uniprot_2": "Q92600"}} +{"question_id": "PPIL3-0144", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: DCP1A (Q9NPI6, 582 AA)\n Function: Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:12417715). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12417715). Contributes to the transactivation of target genes after stimulation by TGFB1 (PubMed:11836524). Essential for embryonic development (PubMed:33813271)\n Location: Cytoplasm, P-body\n Domains: None\n\nProtein 2: NXF5 (Q9H1B4, 397 AA)\n Function: Could be involved in the export of mRNA from the nucleus to the cytoplasm. Could also have a role in polarized cytoplasmic transport and localization of mRNA in neurons\n Location: Cytoplasm\n Domains: NTF2; truncated; RRM\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 738665, "gene_symbol_1": "DCP1A", "gene_symbol_2": "NXF5", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9NPI6", "uniprot_2": "Q9H1B4"}} +{"question_id": "PPIL3-0145", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BRMS1 (Q9HCU9, 246 AA)\n Function: Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma\n Location: Nucleus\n Domains: None\n\nProtein 2: THOC3 (Q96J01, 351 AA)\n Function: Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Required for efficient export of polyadenylated RNA and spliced mRNA (PubMed:23222130). The THOC1-THOC2-THOC3 core complex alone is sufficient to bind export factor NXF1-NXT1 and promote ATPase activity of DDX39B (PubMed:33191911). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 651196, "gene_symbol_1": "BRMS1", "gene_symbol_2": "THOC3", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9HCU9", "uniprot_2": "Q96J01"}} +{"question_id": "PPIL3-0146", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: STAU1 (O95793, 577 AA)\n Function: Binds double-stranded RNA (regardless of the sequence) and tubulin. May play a role in specific positioning of mRNAs at given sites in the cell by cross-linking cytoskeletal and RNA components, and in stimulating their translation at the site\n Location: Cytoplasm\n Domains: DRBM 1; DRBM 2; DRBM 3\n\nProtein 2: ARHGEF3 (Q9NR81, 526 AA)\n Function: Acts as a guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases\n Location: Cytoplasm\n Domains: DH; PH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 113408, "gene_symbol_1": "STAU1", "gene_symbol_2": "ARHGEF3", "detection_method": null, "compartment_type": "same", "uniprot_1": "O95793", "uniprot_2": "Q9NR81"}} +{"question_id": "PPIL3-0147", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: KDM6A (O15550, 1401 AA)\n Function: Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17761849, PubMed:17851529). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17713478, PubMed:17761849, PubMed:17851529). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity)\n Location: Nucleus\n Domains: JmjC\n\nProtein 2: ULK1 (O75385, 1050 AA)\n Function: Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165, PubMed:39384743). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708)\n Location: Cytoplasm, cytosol\n Domains: Protein kinase\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1173573, "gene_symbol_1": "KDM6A", "gene_symbol_2": "ULK1", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15550", "uniprot_2": "O75385"}} +{"question_id": "PPIL3-0148", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CECR2 (Q9BXF3, 1484 AA)\n Function: Regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:15640247, PubMed:22464331, PubMed:26365797, PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The CERF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the CERF-5 ISWI chromatin remodeling complex (PubMed:28801535). Plays a role in various processes during development: required during embryogenesis for neural tube closure and inner ear development. In adults, required for spermatogenesis, via the formation of ISWI-type chromatin complexes (By similarity). In histone-modifying complexes, CECR2 recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated (PubMed:22464331, PubMed:26365797). May also be involved through its interaction with LRPPRC in the integration of cytoskeletal network with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling and cytokinesis (PubMed:11827465)\n Location: Nucleus\n Domains: Bromo\n\nProtein 2: RSF1 (Q96T23, 1441 AA)\n Function: Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984)\n Location: Nucleus\n Domains: DDT\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1061061, "gene_symbol_1": "CECR2", "gene_symbol_2": "RSF1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9BXF3", "uniprot_2": "Q96T23"}} +{"question_id": "PPIL3-0149", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: PSCA (O43653, 114 AA)\n Function: May be involved in the regulation of cell proliferation. Has a cell-proliferation inhibition activity in vitro\n Location: Cell membrane\n Domains: UPAR/Ly6\n\nProtein 2: IL13RA2 (Q14627, 380 AA)\n Function: Cell surface receptor that plays a role in the regulation of IL-13-mediated responses (PubMed:11861389, PubMed:17030238). Functions as a decoy receptor that inhibits IL-13- and IL-4-mediated signal transduction via the JAK-STAT pathway and thereby modulates immune responses and inflammation (PubMed:11861389, PubMed:17030238). Serves as a functional signaling receptor for IL-13 in an alternative pathway involving AP-1 ultimately leading to the production of TGFB1 (PubMed:16327802)\n Location: Cell membrane\n Domains: Fibronectin type-III 1; Fibronectin type-III 2; Fibronectin type-III 3\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 64753, "gene_symbol_1": "PSCA", "gene_symbol_2": "IL13RA2", "detection_method": null, "compartment_type": "same", "uniprot_1": "O43653", "uniprot_2": "Q14627"}} +{"question_id": "PPIL3-0150", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: POLE2 (P56282, 527 AA)\n Function: Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity)\n Location: Nucleus\n Domains: None\n\nProtein 2: PARD6A (Q9NPB6, 346 AA)\n Function: Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in the formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10873802). Regulates centrosome organization and function. Essential for the centrosomal recruitment of key proteins that control centrosomal microtubule organization (PubMed:20719959)\n Location: Cytoplasm\n Domains: PB1; PDZ; Pseudo-CRIB\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1585853, "gene_symbol_1": "POLE2", "gene_symbol_2": "PARD6A", "detection_method": null, "compartment_type": "different", "uniprot_1": "P56282", "uniprot_2": "Q9NPB6"}} +{"question_id": "PPIL3-0151", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: KATNA1 (O75449, 491 AA)\n Function: Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth\n Location: Cytoplasm\n Domains: None\n\nProtein 2: CRB1 (P82279, 1406 AA)\n Function: Plays a role in photoreceptor morphogenesis in the retina (By similarity). May maintain cell polarization and adhesion (By similarity)\n Location: Apical cell membrane\n Domains: EGF-like 1; EGF-like 10; calcium-binding; EGF-like 11; EGF-like 12; EGF-like 13; EGF-like 14; EGF-like 15; EGF-like 16; calcium-binding; EGF-like 17; EGF-like 18; EGF-like 19; calcium-binding; EGF-like 2; EGF-like 3; EGF-like 4; calcium-binding; EGF-like 5; calcium-binding; EGF-like 6; calcium-binding; EGF-like 7; calcium-binding; EGF-like 8; EGF-like 9; Laminin G-like 1; Laminin G-like 2; Laminin G-like 3\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 538554, "gene_symbol_1": "KATNA1", "gene_symbol_2": "CRB1", "detection_method": null, "compartment_type": "different", "uniprot_1": "O75449", "uniprot_2": "P82279"}} +{"question_id": "PPIL3-0152", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: USP22 (Q9UPT9, 525 AA)\n Function: Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity. As part of the transcription regulatory histone acetylation (HAT) complex SAGA, catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a transcriptional coactivator (PubMed:18206972, PubMed:18206973, PubMed:18469533). Recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Facilitates cell-cycle progression by stabilizing CCNB1 and antagonizing its proteasome-mediated degradation in a cell cycle-specific manner (PubMed:27030811). Modulates cell cycle progression and apoptosis also by antagonizing TP53 transcriptional activation through deacetylase SIRT1 stabilization (PubMed:22542455). Plays multiple roles in immunity and inflammation. Participates in antiviral response by deubiquitinating the importin KPNA2, leading to IRF3 nuclear translocation and subsequent type I interferon production (PubMed:32130408). Acts as a central regulator of type III IFN signaling by negatively regulating STING1 activation and ubiquitination (PubMed:35933402). Inhibits NLRP3 inflammasome activation by promoting NLRP3 degradation through ATG5-dependent autophagy (By similarity). Deubiquitinates CD274 to induce its stabilization and thereby participates in maintenance of immune tolerance to self (PubMed:31399419). Controls necroptotic cell death by regulating RIPK3 phosphorylation and ubiquitination (PubMed:33369872). During bacterial infection, promotes pro-inflammatory response by targeting TRAF6 and removing its 'Lys-48'-linked polyubiquitination (By similarity)\n Location: Nucleus\n Domains: USP\n\nProtein 2: RUVBL2 (Q9Y230, 463 AA)\n Function: Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026)\n Location: Nucleus matrix\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 845438, "gene_symbol_1": "USP22", "gene_symbol_2": "RUVBL2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9UPT9", "uniprot_2": "Q9Y230"}} +{"question_id": "PPIL3-0153", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CSNK2A2 (P19784, 350 AA)\n Function: Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:30898438). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:11704824, PubMed:16193064, PubMed:30898438). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387551, PubMed:19387552). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage (PubMed:12631575, PubMed:19387551, PubMed:19387552). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation (PubMed:11239457). Phosphorylates a number of DNA repair proteins in response to DNA damage, such as MDC1, RAD9A, RAD51 and HTATSF1, promoting their recruitment to DNA damage sites (PubMed:20545769, PubMed:21482717, PubMed:22325354, PubMed:26811421, PubMed:30898438, PubMed:35597237). Can also negatively regulate apoptosis (PubMed:19387551, PubMed:19387552). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:12631575, PubMed:19387551, PubMed:19387552). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:12631575, PubMed:19387551, PubMed:19387552). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (PubMed:12631575, PubMed:19387551, PubMed:19387552). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB (PubMed:12631575, PubMed:19387551, PubMed:19387552). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (PubMed:19387550). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:19387549). Acts as an ectokinase that phosphorylates several extracellular proteins (PubMed:12631575, PubMed:19387551, PubMed:19387552). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (PubMed:12631575, PubMed:19387551, PubMed:19387552). May phosphorylate histone H2A on 'Ser-1' (PubMed:38334665)\n Location: Nucleus\n Domains: Protein kinase\n\nProtein 2: C2orf49 (Q9BVC5, 232 AA)\n Function: Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity and may function toward other RNAs\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1202901, "gene_symbol_1": "CSNK2A2", "gene_symbol_2": "C2orf49", "detection_method": null, "compartment_type": "same", "uniprot_1": "P19784", "uniprot_2": "Q9BVC5"}} +{"question_id": "PPIL3-0154", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NCBP1 (Q09161, 790 AA)\n Function: Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability (PubMed:26382858)\n Location: Nucleus\n Domains: MIF4G\n\nProtein 2: NBN (O60934, 754 AA)\n Function: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:10888888, PubMed:15616588, PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:19759395, PubMed:23115235, PubMed:28216226, PubMed:28867292, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:19759395, PubMed:28867292, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:19759395, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:19759395, PubMed:28867292, PubMed:9705271). Within the MRN complex, NBN acts as a protein-protein adapter, which specifically recognizes and binds phosphorylated proteins, promoting their recruitment to DNA damage sites (PubMed:12419185, PubMed:15616588, PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890, PubMed:19759395, PubMed:19804756, PubMed:23762398, PubMed:24534091, PubMed:27814491, PubMed:27889449, PubMed:33836577). Recruits MRE11 and RAD50 components of the MRN complex to DSBs in response to DNA damage (PubMed:12419185, PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:24534091, PubMed:26438602). Promotes the recruitment of PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites, activating their functions (PubMed:15064416, PubMed:15616588, PubMed:15790808, PubMed:16622404, PubMed:22464731, PubMed:30952868, PubMed:35076389). Mediates the recruitment of phosphorylated RBBP8/CtIP to DSBs, leading to cooperation between the MRN complex and RBBP8/CtIP to initiate end resection (PubMed:19759395, PubMed:27814491, PubMed:27889449, PubMed:33836577). RBBP8/CtIP specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts (PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:33836577). The MRN complex is also required for the processing of R-loops (PubMed:31537797). NBN also functions in telomere length maintenance via its interaction with TERF2: interaction with TERF2 during G1 phase preventing recruitment of DCLRE1B/Apollo to telomeres (PubMed:10888888, PubMed:28216226). NBN also promotes DNA repair choice at dysfunctional telomeres: NBN phosphorylation by CDK2 promotes non-homologous end joining repair at telomeres, while unphosphorylated NBN promotes microhomology-mediated end-joining (MMEJ) repair (PubMed:28216226). Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex (PubMed:23762398)\n Location: Nucleus\n Domains: BRCT 1; BRCT 2; FHA\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1280099, "gene_symbol_1": "NCBP1", "gene_symbol_2": "NBN", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q09161", "uniprot_2": "O60934"}} +{"question_id": "PPIL3-0155", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RUVBL1 (Q9Y265, 456 AA)\n Function: Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). Essential for cell proliferation (PubMed:14506706). May be able to bind plasminogen at cell surface and enhance plasminogen activation (PubMed:11027681)\n Location: Nucleus matrix\n Domains: None\n\nProtein 2: INCENP (Q9NQS7, 918 AA)\n Function: Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules (PubMed:12925766, PubMed:15316025, PubMed:27332895). The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC (PubMed:27332895). Required for localization of CBX5 to mitotic centromeres (PubMed:21346195). Controls the kinetochore localization of BUB1 (PubMed:16760428)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 910531, "gene_symbol_1": "RUVBL1", "gene_symbol_2": "INCENP", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9Y265", "uniprot_2": "Q9NQS7"}} +{"question_id": "PPIL3-0156", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CENPS (Q8N2Z9, 138 AA)\n Function: DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:20347428, PubMed:20347429). In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM (PubMed:20347428, PubMed:20347429). In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks (PubMed:20347428). In complex with CENPT, CENPW and CENPX (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression (PubMed:19620631). As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure (PubMed:20347428, PubMed:22304917). DNA-binding function is fulfilled in the presence of CENPX, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own (PubMed:20347428, PubMed:20347429)\n Location: Nucleus\n Domains: None\n\nProtein 2: PIK3R6 (Q5UE93, 754 AA)\n Function: Regulatory subunit of the PI3K gamma complex. Acts as an adapter to drive activation of PIK3CG by beta-gamma G protein dimers. The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G protein dimers than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. Recruits of the PI3K gamma complex to a PDE3B:RAPGEF3 signaling complex involved in angiogenesis; signaling seems to involve RRAS\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1597452, "gene_symbol_1": "CENPS", "gene_symbol_2": "PIK3R6", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q8N2Z9", "uniprot_2": "Q5UE93"}} +{"question_id": "PPIL3-0157", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: AP1S1 (P61966, 158 AA)\n Function: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules\n Location: Golgi apparatus\n Domains: None\n\nProtein 2: SAE1 (Q9UBE0, 346 AA)\n Function: The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1612524, "gene_symbol_1": "AP1S1", "gene_symbol_2": "SAE1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P61966", "uniprot_2": "Q9UBE0"}} +{"question_id": "PPIL3-0158", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ZNHIT1 (O43257, 154 AA)\n Function: Plays a role in chromatin remodeling by promoting the incorporation of histone variant H2AZ1/H2A.Z into the genome to regulate gene expression (PubMed:20473270, PubMed:35175558). Promotes SRCAP complex-mediated deposition of histone variant H2AZ1 to lymphoid fate regulator genes, enhancing lymphoid lineage commitment (By similarity). Recruited to the promoter of the transcriptional activator MYOG at the early stages of muscle differentiation where it mediates binding of histone H2AZ1 to chromatin and induces muscle-specific gene expression (PubMed:20473270). Maintains hematopoietic stem cell (HSC) quiescence by determining the chromatin accessibility at distal enhancers of HSC quiescence genes such as PTEN, FSTL1 and KLF4, enhancing deposition of H2AZ1 to promote their sustained transcription and restricting PI3K-AKT signaling inhibition (By similarity). Plays a role in intestinal stem cell maintenance by promoting H2AZ1 deposition at the transcription start sites of genes involved in intestinal stem cell fate determination including LGR5, TGFB1 and TGFBR2, thereby contributing to gene transcription (By similarity). Promotes phosphorylation of the H2AZ1 chaperone VPS72/YL1 which enhances the interaction between HZAZ1 and VPS72 (By similarity). Regulates the entry of male germ cells into meiosis by controlling histone H2AZ1 deposition which facilitates the expression of meiotic genes such as MEIOSIN, leading to the initiation of meiosis (By similarity). Required for postnatal heart function through its role in maintenance of cardiac Ca(2+) homeostasis by modulating the expression of Ca(2+)-regulating proteins CASQ1 and ATP2A2/SERCA2A via deposition of histone H2AZ1 at their promoters (By similarity). During embryonic heart development, required for mitochondrial maturation and oxidative metabolism by functioning through H2AZ1 deposition to activate transcription of metabolic genes and is also required to maintain the stability of the respiratory complex (By similarity). In neural cells, increases deposition of the H2AZ1 histone variant and promotes neurite growth (PubMed:35175558). Plays a role in TP53/p53-mediated apoptosis induction by stimulating the transcriptional activation of several proapoptotic p53 target genes such as PMAIP1/NOXA and BBC3/PUMA (PubMed:17380123). Mediates cell cycle arrest induced in response to gamma-irradiation by enhancing recruitment of TP53/p53 to the promoter of the cell cycle inhibitor CDKN1A, leading to its transcriptional activation (PubMed:17700068). Recruited to the promoter of cyclin-dependent kinase CDK6 and inhibits its transcription, possibly by decreasing the acetylation level of histone H4, leading to cell cycle arrest at the G1 phase (By similarity). Plays a role in lens fiber cell differentiation by regulating the expression of cell cycle regulator CDKN1A/p21Cip1 (By similarity). Binds to transcriptional repressor NR1D2 and relieves it of its inhibitory effect on the transcription of apolipoprotein APOC3 without affecting its DNA-binding activity (PubMed:17892483)\n Location: Nucleus\n Domains: None\n\nProtein 2: TRRAP (Q9Y4A5, 3859 AA)\n Function: Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. Component of the NuA4 histone acetyltransferase complex which is responsible for acetylation of nucleosomal histones H4 and H2A. Plays a central role in MYC transcription activation, and also participates in cell transformation by MYC. Required for p53/TP53-, E2F1- and E2F4-mediated transcription activation. Also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes. Probably acts by linking transcription factors such as E1A, MYC or E2F1 to HAT complexes such as STAGA thereby allowing transcription activation. Probably not required in the steps following histone acetylation in processes of transcription activation. May be required for the mitotic checkpoint and normal cell cycle progression. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. May play a role in the formation and maintenance of the auditory system (By similarity)\n Location: Nucleus\n Domains: FAT; FATC; PI3K/PI4K catalytic\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1227874, "gene_symbol_1": "ZNHIT1", "gene_symbol_2": "TRRAP", "detection_method": null, "compartment_type": "same", "uniprot_1": "O43257", "uniprot_2": "Q9Y4A5"}} +{"question_id": "PPIL3-0159", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CCT2 (P78371, 535 AA)\n Function: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: MVB12A (Q96EY5, 273 AA)\n Function: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor\n Location: Cytoplasm\n Domains: MABP; UMA\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1598497, "gene_symbol_1": "CCT2", "gene_symbol_2": "MVB12A", "detection_method": null, "compartment_type": "same", "uniprot_1": "P78371", "uniprot_2": "Q96EY5"}} +{"question_id": "PPIL3-0160", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MAFG (O15525, 162 AA)\n Function: Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (PubMed:11154691). However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1 and NFE2L2, and recruiting them to specific DNA-binding sites (PubMed:11154691, PubMed:8932385, PubMed:9421508). Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NFE2L2 transcription factor (PubMed:11154691). Transcription factor, component of erythroid-specific transcription factor NFE2L2 (PubMed:11154691). Activates globin gene expression when associated with NFE2L2 (PubMed:11154691). May be involved in signal transduction of extracellular H(+) (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nProtein 2: AZI2 (Q9H6S1, 392 AA)\n Function: Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomerization (PubMed:14560022, PubMed:21931631). Enhances the phosphorylation of NF-kappa-B p65 subunit RELA by TBK1 (PubMed:14560022, PubMed:21931631). Promotes TBK1-induced as well as TNF or PMA-induced activation of NF-kappa-B (PubMed:14560022, PubMed:21931631). Participates in IFNB promoter activation via TICAM1 (PubMed:15611223)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1584228, "gene_symbol_1": "MAFG", "gene_symbol_2": "AZI2", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15525", "uniprot_2": "Q9H6S1"}} +{"question_id": "PPIL3-0161", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TFAM (Q00059, 246 AA)\n Function: Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (PubMed:29445193, PubMed:32183942). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (PubMed:29149603). In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:20410300). Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase (PubMed:22037172). Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites (PubMed:22037172). Is able to unwind DNA (PubMed:22037172). Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes (PubMed:1737790). Required for maintenance of normal levels of mitochondrial DNA (PubMed:19304746, PubMed:22841477). May play a role in organizing and compacting mitochondrial DNA (PubMed:22037171)\n Location: Mitochondrion\n Domains: None\n\nProtein 2: ZBTB8OS (Q8IWT0, 167 AA)\n Function: Activation factor of RTCB, the catalytic subunit of the tRNA-splicing ligase complex (tRNA-LC), which is involved in the enzyme-dependent maturation of intron-containing pre-tRNAs. Functions downstream of the tRNA-splicing endonuclease that removes introns, ligating the two generated halves via phosphodiester bond formation. Catalyzes the GTP-dependent activation of RTCB, both proteins forming a composite active site coordinating GTP and metal ions to enable the guanylylation of RTCB a prerequisite to undergo multiple catalytic cycles (PubMed:24870230, PubMed:38493148). Also required for the activation of RTCB in non-canonical, spliceosome-independent, cytoplasmic splicing of XBP1 mRNAs during the unfolded protein response (UPR). Upon endoplasmic reticulum (ER) stress, the endoribonuclease IRE1/ERN1 excises a short intron, generating free exon ends that are aligned by RNA-intrinsic, zipper-like stem-loop structures. These exon ends are then recognized and ligated by RTCB. This splicing event yields the active XBP1s transcription factor, which induces genes required to resolve protein folding defects in the endoplasmic reticulum (PubMed:25378478, PubMed:26483401, PubMed:38493148)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1390407, "gene_symbol_1": "TFAM", "gene_symbol_2": "ZBTB8OS", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q00059", "uniprot_2": "Q8IWT0"}} +{"question_id": "PPIL3-0162", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RAD23B (P54727, 409 AA)\n Function: Multifunctional protein that participates in histone H4K20 demethylation, DNA repair, ubiquitin-dependent protein degradation and transcriptional regulation (PubMed:10488153, PubMed:32209475, PubMed:9372924). Specifically demethylates mono-, di- and trimethylated 'Lys-20' of histone H4 (H4K20me1, H4K20me2, H4K20me3, respectively) into unmethylated forms. Activates the transcription of coding genes by demethylating H4K20me1 and the transcription of repetitive elements by demethylating H4K20me3 (PubMed:32209475). Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome (PubMed:10488153, PubMed:19435460). May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome (PubMed:15358861). Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex, a nucleotide-excision repair complex that is involved in damage sensing during global genome nucleotide excision repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA. Recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix including single-stranded loops, mismatched bubbles or single-stranded overhangs. Cooperatively with CETN2 appears to stabilize XPC (PubMed:10873465, PubMed:12815074, PubMed:9372924)\n Location: Nucleus\n Domains: STI1; UBA 1; UBA 2; Ubiquitin-like\n\nProtein 2: SEC11A (P67812, 179 AA)\n Function: Catalytic component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (PubMed:34388369). Specifically cleaves N-terminal signal peptides that contain a hydrophobic alpha-helix (h-region) shorter than 18-20 amino acids (PubMed:34388369)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1027786, "gene_symbol_1": "RAD23B", "gene_symbol_2": "SEC11A", "detection_method": null, "compartment_type": "different", "uniprot_1": "P54727", "uniprot_2": "P67812"}} +{"question_id": "PPIL3-0163", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: EXOSC7 (Q15024, 291 AA)\n Function: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes\n Location: Nucleus, nucleolus\n Domains: None\n\nProtein 2: SPTSSB (Q8NFR3, 76 AA)\n Function: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases (PubMed:19416851). The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core (PubMed:19416851). Within the SPT complex, SPTSSB stimulates the catalytic activity and plays a role in substrate specificity. SPT complexes with this subunit showing a preference for longer acyl-CoAs. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1529937, "gene_symbol_1": "EXOSC7", "gene_symbol_2": "SPTSSB", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q15024", "uniprot_2": "Q8NFR3"}} +{"question_id": "PPIL3-0164", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MSN (P26038, 577 AA)\n Function: Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (PubMed:10212266). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (PubMed:12387735, PubMed:15039356). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:9298994, PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By similarity). Also participates in immunologic synapse formation (PubMed:27405666)\n Location: Cell membrane\n Domains: FERM\n\nProtein 2: CYBRD1 (Q53TN4, 286 AA)\n Function: Plasma membrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) into Fe(2+) (PubMed:30272000). Probably functions in dietary iron absorption at the brush border of duodenal enterocytes by producing Fe(2+), the divalent form of iron that can be transported into enterocytes (PubMed:30272000). It is also able to reduce extracellular monodehydro-L-ascorbate and may be involved in extracellular ascorbate regeneration by erythrocytes in blood (PubMed:17068337). May also act as a ferrireductase in airway epithelial cells (Probable). May also function as a cupric transmembrane reductase (By similarity)\n Location: Cell membrane\n Domains: Cytochrome b561\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 189170, "gene_symbol_1": "MSN", "gene_symbol_2": "CYBRD1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P26038", "uniprot_2": "Q53TN4"}} +{"question_id": "PPIL3-0165", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CCND3 (P30281, 292 AA)\n Function: Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:8114739). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:8114739). Hypophosphorylates RB1 in early G(1) phase (PubMed:8114739). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:8114739). Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:16782892). Shows transcriptional coactivator activity with ATF5 independently of CDK4 (PubMed:15358120)\n Location: Nucleus\n Domains: Cyclin N-terminal\n\nProtein 2: POLR2J (P52435, 117 AA)\n Function: Core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 198271, "gene_symbol_1": "CCND3", "gene_symbol_2": "POLR2J", "detection_method": null, "compartment_type": "same", "uniprot_1": "P30281", "uniprot_2": "P52435"}} +{"question_id": "PPIL3-0166", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BLOC1S2 (Q6QNY1, 142 AA)\n Function: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes (PubMed:15102850, PubMed:17182842). In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension (By similarity). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (PubMed:25898167). May play a role in cell proliferation (PubMed:15381421)\n Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome\n Domains: None\n\nProtein 2: MTOR (P42345, 2549 AA)\n Function: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity)\n Location: Lysosome membrane\n Domains: FAT; FATC; PI3K/PI4K catalytic\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 833472, "gene_symbol_1": "BLOC1S2", "gene_symbol_2": "MTOR", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q6QNY1", "uniprot_2": "P42345"}} +{"question_id": "PPIL3-0167", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CDC5L (Q99459, 802 AA)\n Function: DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30705154, PubMed:30728453). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable)\n Location: Nucleus\n Domains: HTH myb-type 1; HTH myb-type 2\n\nProtein 2: EPC1 (Q9H2F5, 836 AA)\n Function: Component of the NuA4 histone acetyltransferase (HAT) complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR) (PubMed:27153538). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone acetylation is required for histone replacement during the transition from round to elongating spermatids (By similarity). In the NuA4 complex, EPC1 is required to recruit MBTD1 into the complex (PubMed:32209463)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 700931, "gene_symbol_1": "CDC5L", "gene_symbol_2": "EPC1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q99459", "uniprot_2": "Q9H2F5"}} +{"question_id": "PPIL3-0168", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: PFKL (P17858, 780 AA)\n Function: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (By similarity)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: HSPA9 (P38646, 679 AA)\n Function: Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382)\n Location: Mitochondrion\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1514557, "gene_symbol_1": "PFKL", "gene_symbol_2": "HSPA9", "detection_method": null, "compartment_type": "different", "uniprot_1": "P17858", "uniprot_2": "P38646"}} +{"question_id": "PPIL3-0169", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: EXOC3L1 (Q86VI1, 746 AA)\n Function: As part of the exocyst, may play a role in regulated exocytosis of insulin granules\n Location: Cytoplasmic vesicle, secretory vesicle\n Domains: None\n\nProtein 2: RSPH9 (Q9H1X1, 276 AA)\n Function: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:19200523). Essential for both the radial spoke head assembly and the central pair microtubule stability in ependymal motile cilia (By similarity). Required for motility of olfactory and neural cilia and for the structural integrity of ciliary axonemes in both 9+0 and 9+2 motile cilia (By similarity)\n Location: Cytoplasm, cytoskeleton, cilium axoneme\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 396441, "gene_symbol_1": "EXOC3L1", "gene_symbol_2": "RSPH9", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q86VI1", "uniprot_2": "Q9H1X1"}} +{"question_id": "PPIL3-0170", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TRRAP (Q9Y4A5, 3859 AA)\n Function: Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. Component of the NuA4 histone acetyltransferase complex which is responsible for acetylation of nucleosomal histones H4 and H2A. Plays a central role in MYC transcription activation, and also participates in cell transformation by MYC. Required for p53/TP53-, E2F1- and E2F4-mediated transcription activation. Also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes. Probably acts by linking transcription factors such as E1A, MYC or E2F1 to HAT complexes such as STAGA thereby allowing transcription activation. Probably not required in the steps following histone acetylation in processes of transcription activation. May be required for the mitotic checkpoint and normal cell cycle progression. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. May play a role in the formation and maintenance of the auditory system (By similarity)\n Location: Nucleus\n Domains: FAT; FATC; PI3K/PI4K catalytic\n\nProtein 2: MED23 (Q9ULK4, 1368 AA)\n Function: Required for transcriptional activation subsequent to the assembly of the pre-initiation complex (By similarity). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Required for transcriptional activation by adenovirus E1A protein. Required for ELK1-dependent transcriptional activation in response to activated Ras signaling\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1098811, "gene_symbol_1": "TRRAP", "gene_symbol_2": "MED23", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9Y4A5", "uniprot_2": "Q9ULK4"}} +{"question_id": "PPIL3-0171", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MDM4 (O15151, 490 AA)\n Function: Contributes to p53/TP53 regulation (PubMed:32300648). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding their transcriptional activation domains. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions\n Location: Nucleus\n Domains: SWIB/MDM2\n\nProtein 2: TAF4 (O00268, 1085 AA)\n Function: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:10594036, PubMed:33795473, PubMed:8942982). TAF4 may maintain an association between the TFIID and TFIIA complexes, while bound to the promoter, together with TBP, during PIC assembly (PubMed:33795473). Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone (PubMed:9192867)\n Location: Nucleus\n Domains: TAFH\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1138384, "gene_symbol_1": "MDM4", "gene_symbol_2": "TAF4", "detection_method": null, "compartment_type": "same", "uniprot_1": "O15151", "uniprot_2": "O00268"}} +{"question_id": "PPIL3-0172", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SYCE1 (Q8N0S2, 351 AA)\n Function: Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination\n Location: Nucleus\n Domains: None\n\nProtein 2: TSEN2 (Q8NCE0, 465 AA)\n Function: Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Isoform 1 probably carries the active site for 5'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. Isoform 2 is responsible for processing a yet unknown RNA substrate. The complex containing isoform 2 is not able to cleave pre-tRNAs properly, although it retains endonucleolytic activity\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 412078, "gene_symbol_1": "SYCE1", "gene_symbol_2": "TSEN2", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q8N0S2", "uniprot_2": "Q8NCE0"}} +{"question_id": "PPIL3-0173", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: MCM7 (P33993, 719 AA)\n Function: Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for S-phase checkpoint activation upon UV-induced damage\n Location: Nucleus\n Domains: MCM C-terminal AAA(+) ATPase\n\nProtein 2: BATF (Q16520, 125 AA)\n Function: AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8(+) dendritic cells and class-switch recombination (CSR) in B-cells. Acts via the formation of a heterodimer with JUNB that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3'. The BATF-JUNB heterodimer also forms a complex with IRF4 (or IRF8) in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 (or IRF8) and activation of genes. Controls differentiation of T-helper cells producing interleukin-17 (Th17 cells) by binding to Th17-associated gene promoters: regulates expression of the transcription factor RORC itself and RORC target genes such as IL17 (IL17A or IL17B). Also involved in differentiation of follicular T-helper cells (TfH) by directing expression of BCL6 and MAF. In B-cells, involved in class-switch recombination (CSR) by controlling the expression of both AICDA and of germline transcripts of the intervening heavy-chain region and constant heavy-chain region (I(H)-C(H)). Following infection, can participate in CD8(+) dendritic cell differentiation via interaction with IRF4 and IRF8 to mediate cooperative gene activation. Regulates effector CD8(+) T-cell differentiation by regulating expression of SIRT1. Following DNA damage, part of a differentiation checkpoint that limits self-renewal of hematopoietic stem cells (HSCs): up-regulated by STAT3, leading to differentiation of HSCs, thereby restricting self-renewal of HSCs (By similarity)\n Location: Nucleus\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1493257, "gene_symbol_1": "MCM7", "gene_symbol_2": "BATF", "detection_method": null, "compartment_type": "same", "uniprot_1": "P33993", "uniprot_2": "Q16520"}} +{"question_id": "PPIL3-0174", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SS18 (Q15532, 418 AA)\n Function: Appears to function synergistically with RBM14 as a transcriptional coactivator. Isoform 1 and isoform 2 function in nuclear receptor coactivation. Isoform 1 and isoform 2 function in general transcriptional coactivation. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058)\n Location: Nucleus\n Domains: None\n\nProtein 2: IKBKG (Q9Y6K9, 419 AA)\n Function: Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:14695475, PubMed:20724660, PubMed:21518757, PubMed:9751060). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:19185524, PubMed:21606507, PubMed:27777308, PubMed:33567255). Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:19185524, PubMed:21606507, PubMed:27777308). Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3 (PubMed:19854139). Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (PubMed:20724660)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1644769, "gene_symbol_1": "SS18", "gene_symbol_2": "IKBKG", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q15532", "uniprot_2": "Q9Y6K9"}} +{"question_id": "PPIL3-0175", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: TAF9 (Q16594, 264 AA)\n Function: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). TAF9 is also a component of the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex (PubMed:15899866). TAF9 and its paralog TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes (PubMed:15899866). Essential for cell viability (PubMed:15899866). May have a role in gene regulation associated with apoptosis (PubMed:15899866)\n Location: Nucleus\n Domains: None\n\nProtein 2: KPNA3 (O00505, 521 AA)\n Function: Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9\n Location: Cytoplasm\n Domains: IBB\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1510165, "gene_symbol_1": "TAF9", "gene_symbol_2": "KPNA3", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q16594", "uniprot_2": "O00505"}} +{"question_id": "PPIL3-0176", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: PMM2 (O15305, 246 AA)\n Function: Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions\n Location: Cytoplasm\n Domains: None\n\nProtein 2: CD3D (P04234, 171 AA)\n Function: Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly. Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells (PubMed:12215456)\n Location: Cell membrane\n Domains: ITAM\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 51275, "gene_symbol_1": "PMM2", "gene_symbol_2": "CD3D", "detection_method": null, "compartment_type": "different", "uniprot_1": "O15305", "uniprot_2": "P04234"}} +{"question_id": "PPIL3-0177", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RAD21 (O60216, 631 AA)\n Function: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions (PubMed:11509732). The cohesin complex may also play a role in spindle pole assembly during mitosis (PubMed:11590136). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May control RUNX1 gene expression (Probable). Binds to and represses APOB gene promoter (PubMed:25575569). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity)\n Location: Nucleus\n Domains: None\n\nProtein 2: MED21 (Q13503, 144 AA)\n Function: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 519606, "gene_symbol_1": "RAD21", "gene_symbol_2": "MED21", "detection_method": null, "compartment_type": "same", "uniprot_1": "O60216", "uniprot_2": "Q13503"}} +{"question_id": "PPIL3-0178", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NAA38 (Q9BRA0, 125 AA)\n Function: Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues (PubMed:19398576, PubMed:37891180). N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway (PubMed:37891180)\n Location: Cytoplasm\n Domains: Sm\n\nProtein 2: MRPS2 (Q9Y399, 296 AA)\n Function: Required for mitoribosome formation and stability, and mitochondrial translation\n Location: Mitochondrion\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1674535, "gene_symbol_1": "NAA38", "gene_symbol_2": "MRPS2", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9BRA0", "uniprot_2": "Q9Y399"}} +{"question_id": "PPIL3-0179", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ORC1 (Q13415, 861 AA)\n Function: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication\n Location: Nucleus\n Domains: BAH\n\nProtein 2: SPTLC1 (O15269, 473 AA)\n Function: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 872468, "gene_symbol_1": "ORC1", "gene_symbol_2": "SPTLC1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q13415", "uniprot_2": "O15269"}} +{"question_id": "PPIL3-0180", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NUDT21 (O43809, 227 AA)\n Function: Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:14690600, PubMed:15937220, PubMed:17024186, PubMed:17098938, PubMed:29276085, PubMed:8626397, PubMed:9659921). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:14690600, PubMed:17024186, PubMed:8626397, PubMed:9659921). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:17098938, PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:17098938, PubMed:20695905, PubMed:29276085). NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7 (PubMed:29276085). Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing (PubMed:14690600, PubMed:15169763, PubMed:17024186, PubMed:20479262, PubMed:22813749, PubMed:8626397). The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA (PubMed:20479262, PubMed:21295486). Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function (By similarity). Binds to chromatin (By similarity). Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629)\n Location: Nucleus\n Domains: Nudix hydrolase\n\nProtein 2: MAD2L2 (Q9UI95, 211 AA)\n Function: Adapter protein able to interact with different proteins and involved in different biological processes (PubMed:11459825, PubMed:11459826, PubMed:17296730, PubMed:17719540, PubMed:19443654, PubMed:29656893). Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis (PubMed:20164194, PubMed:23143872). Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions (PubMed:20164194). Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1 (PubMed:17296730). Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle (PubMed:11459825, PubMed:17719540). Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation (PubMed:19443654)\n Location: Nucleus\n Domains: HORMA\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1224333, "gene_symbol_1": "NUDT21", "gene_symbol_2": "MAD2L2", "detection_method": null, "compartment_type": "same", "uniprot_1": "O43809", "uniprot_2": "Q9UI95"}} +{"question_id": "PPIL3-0181", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: RNASEH2B (Q5TBB1, 312 AA)\n Function: Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes\n Location: Nucleus\n Domains: None\n\nProtein 2: NXF1 (Q9UBU9, 619 AA)\n Function: Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway) (PubMed:10924507). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex (PubMed:18364396, PubMed:19165146, PubMed:9660949). ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export (PubMed:18364396, PubMed:19165146, PubMed:9660949). Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244)\n Location: Nucleus\n Domains: NTF2; RRM; TAP-C\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1397355, "gene_symbol_1": "RNASEH2B", "gene_symbol_2": "NXF1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q5TBB1", "uniprot_2": "Q9UBU9"}} +{"question_id": "PPIL3-0182", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CAPNS1 (P04632, 268 AA)\n Function: Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Essential for embryonic development (By similarity)\n Location: Cytoplasm\n Domains: EF-hand 1; atypical; EF-hand 2; EF-hand 3; EF-hand 4; EF-hand 5\n\nProtein 2: POT1 (Q9NUX5, 634 AA)\n Function: Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. Is a component of the double-stranded telomeric DNA-binding TRF1 complex which is involved in the regulation of telomere length by cis-inhibition of telomerase. Also acts as a single-stranded telomeric DNA-binding protein and thus may act as a downstream effector of the TRF1 complex and may transduce information about telomere maintenance and/or length to the telomere terminus. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Binds to two or more telomeric single-stranded 5'-TTAGGG-3' repeats (G-strand) and with high specificity to a minimal telomeric single-stranded 5'-TAGGGTTAG-3' sequence. Binds telomeric single-stranded sequences internally or at proximity of a 3'-end. Its activity is TERT dependent but it does not increase TERT activity by itself. In contrast, the ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 857291, "gene_symbol_1": "CAPNS1", "gene_symbol_2": "POT1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P04632", "uniprot_2": "Q9NUX5"}} +{"question_id": "PPIL3-0183", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ITGB7 (P26010, 798 AA)\n Function: Integrin ITGA4/ITGB7 (alpha-4/beta-7) (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT) (Probable). Integrin ITGA4/ITGB7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract (PubMed:10837471, PubMed:14608374). Also interacts with VCAM1 and fibronectin, an extracellular matrix component (Probable). It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin (Probable). Interactions involve the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin (Probable). Integrin ITGAE/ITGB7 (alpha-E/beta-7, HML-1) is a receptor for E-cadherin (PubMed:10837471)\n Location: Cell membrane\n Domains: I-EGF 1; I-EGF 2; I-EGF 3; I-EGF 4; PSI; VWFA\n\nProtein 2: ZC3H8 (Q8N5P1, 291 AA)\n Function: Acts as a transcriptional repressor of the GATA3 promoter. Sequence-specific DNA-binding factor that binds to the 5'-AGGTCTC-3' sequence within the negative cis-acting element intronic regulatory region (IRR) of the GATA3 gene (By similarity). Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:23932780). Induces thymocyte apoptosis when overexpressed, which may indicate a role in regulation of thymocyte homeostasis\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 995193, "gene_symbol_1": "ITGB7", "gene_symbol_2": "ZC3H8", "detection_method": null, "compartment_type": "different", "uniprot_1": "P26010", "uniprot_2": "Q8N5P1"}} +{"question_id": "PPIL3-0184", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: COXFA4 (O00483, 81 AA)\n Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (PubMed:22902835). COXFA4 is required for complex IV maintenance (PubMed:22902835)\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: STIL (Q15468, 1287 AA)\n Function: Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CPAP to the base of the procentriole to initiate procentriole assembly (PubMed:22020124). In complex with STIL acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility (PubMed:29712910, PubMed:32107292)\n Location: Cytoplasm, cytosol\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1490450, "gene_symbol_1": "COXFA4", "gene_symbol_2": "STIL", "detection_method": null, "compartment_type": "different", "uniprot_1": "O00483", "uniprot_2": "Q15468"}} +{"question_id": "PPIL3-0185", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ERLIN1 (O75477, 348 AA)\n Function: Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway (PubMed:37683630). Binds cholesterol and may promote ER retention of the SCAP-SREBF complex (PubMed:24217618)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nProtein 2: POLD3 (Q15054, 466 AA)\n Function: Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the tetrameric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906)\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 987594, "gene_symbol_1": "ERLIN1", "gene_symbol_2": "POLD3", "detection_method": null, "compartment_type": "different", "uniprot_1": "O75477", "uniprot_2": "Q15054"}} +{"question_id": "PPIL3-0186", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BCL2 (P10415, 239 AA)\n Function: Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondrial membrane permeability (PubMed:11368354). Appears to function in a feedback loop system with caspases (PubMed:11368354). Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1) (PubMed:11368354). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function (PubMed:18570871, PubMed:20889974, PubMed:21358617). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785)\n Location: Mitochondrion outer membrane\n Domains: None\n\nProtein 2: UTRN (P46939, 3433 AA)\n Function: May play a role in anchoring the cytoskeleton to the plasma membrane\n Location: Postsynaptic cell membrane\n Domains: Calponin-homology (CH) 1; Calponin-homology (CH) 2; WW\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1580641, "gene_symbol_1": "BCL2", "gene_symbol_2": "UTRN", "detection_method": null, "compartment_type": "same", "uniprot_1": "P10415", "uniprot_2": "P46939"}} +{"question_id": "PPIL3-0187", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SLC39A6 (Q13433, 755 AA)\n Function: Zinc-influx transporter which plays a role in zinc homeostasis and in the induction of epithelial-to-mesenchymal transition (EMT) (PubMed:12839489, PubMed:18272141, PubMed:21422171, PubMed:23919497, PubMed:27274087, PubMed:34394081). When associated with SLC39A10, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial- to-mesenchymal transition (EMT) (PubMed:27274087). The SLC39A10-SLC39A6 heterodimer also controls NCAM1 phosphorylation and its integration into focal adhesion complexes during EMT (By similarity). Zinc influx inactivates GSK3B, enabling unphosphorylated SNAI1 in the nucleus to down-regulate adherence genes such as CDH1, causing loss of cell adherence (PubMed:23919497). In addition, the SLC39A10-SLC39A6 heterodimer plays an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (PubMed:32797246). Participates in the T-cell receptor signaling regulation by mediating cellular zinc uptake into activated lymphocytes (PubMed:21422171, PubMed:30552163, PubMed:34394081). Regulates the zinc influx necessary for proper meiotic progression to metaphase II (MII) that allows the oocyte-to-egg transition (PubMed:25143461)\n Location: Cell membrane\n Domains: None\n\nProtein 2: SCNM1 (Q9BWG6, 230 AA)\n Function: As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:36084634). Plays a role in the regulation of primary cilia length and Hedgehog signaling (PubMed:36084634)\n Location: Nucleus, nucleoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 297194, "gene_symbol_1": "SLC39A6", "gene_symbol_2": "SCNM1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q13433", "uniprot_2": "Q9BWG6"}} +{"question_id": "PPIL3-0188", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: SPINDOC (Q9BUA3, 381 AA)\n Function: Chromatin protein that stabilizes SPIN1 and enhances its association with histone H3 trimethylated at both 'Lys-4' and 'Lys-9' (H3K4me3K9me3) (PubMed:33574238). Positively regulates poly-ADP-ribosylation in response to DNA damage; acts by facilitating PARP1 ADP-ribosyltransferase activity (PubMed:34737271)\n Location: Nucleus\n Domains: None\n\nProtein 2: LHX3 (Q9UBR4, 397 AA)\n Function: Transcription factor. Recognizes and binds to the consensus sequence motif 5'-AATTAATTA-3' in the regulatory elements of target genes, such as glycoprotein hormones alpha chain CGA and visual system homeobox CHX10, positively modulating transcription; transcription can be co-activated by LDB2. Synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (By similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system (PubMed:21149718). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1 (By similarity)\n Location: Nucleus\n Domains: LIM zinc-binding 1; LIM zinc-binding 2\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 477866, "gene_symbol_1": "SPINDOC", "gene_symbol_2": "LHX3", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9BUA3", "uniprot_2": "Q9UBR4"}} +{"question_id": "PPIL3-0189", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ANXA1 (P04083, 346 AA)\n Function: Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T cells (PubMed:17008549). Promotes the differentiation of T cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). In the context of antitumor immunity, interacts with FPR1 on dendritic cells allowing for tumor-associated antigens uptake and cross-presentation to T cells to mount an antitumor specific T cell response\n Location: Nucleus\n Domains: None\n\nProtein 2: RNF2 (Q99496, 336 AA)\n Function: E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation (PubMed:15386022, PubMed:16359901, PubMed:21772249, PubMed:25355358, PubMed:25519132, PubMed:26151332, PubMed:33864376). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation (By similarity). Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:16359901, PubMed:26151332). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:26151332). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:21772249). Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (Probable). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes (By similarity). Also acts as a negative regulator of autophagy by mediating ubiquitination of AMBRA1, leading to its subsequent degradation (By similarity)\n Location: Nucleus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 127994, "gene_symbol_1": "ANXA1", "gene_symbol_2": "RNF2", "detection_method": null, "compartment_type": "same", "uniprot_1": "P04083", "uniprot_2": "Q99496"}} +{"question_id": "PPIL3-0190", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATP6V1B1 (P15313, 513 AA)\n Function: Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:16769747). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). Essential for the proper assembly and activity of V-ATPase (PubMed:16769747). In renal intercalated cells, mediates secretion of protons (H+) into the urine thereby ensuring correct urinary acidification (PubMed:16769747). Required for optimal olfactory function by mediating the acidification of the nasal olfactory epithelium (By similarity)\n Location: Apical cell membrane\n Domains: None\n\nProtein 2: SIRT1 (Q96EB6, 747 AA)\n Function: NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy (PubMed:11672523, PubMed:12006491, PubMed:14976264, PubMed:14980222, PubMed:15126506, PubMed:15152190, PubMed:15205477, PubMed:15469825, PubMed:15692560, PubMed:16079181, PubMed:16166628, PubMed:16892051, PubMed:16998810, PubMed:17283066, PubMed:17290224, PubMed:17334224, PubMed:17505061, PubMed:17612497, PubMed:17620057, PubMed:17936707, PubMed:18203716, PubMed:18296641, PubMed:18662546, PubMed:18687677, PubMed:19188449, PubMed:19220062, PubMed:19364925, PubMed:19690166, PubMed:19934257, PubMed:20097625, PubMed:20100829, PubMed:20203304, PubMed:20375098, PubMed:20620956, PubMed:20670893, PubMed:20817729, PubMed:20955178, PubMed:21149730, PubMed:21245319, PubMed:21471201, PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047, PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893, PubMed:21947282, PubMed:22274616, PubMed:22918831, PubMed:24415752, PubMed:24824780, PubMed:29681526, PubMed:29765047, PubMed:30409912). Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression (PubMed:15469825). Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively (PubMed:14976264, PubMed:14980222, PubMed:15152190). Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction (PubMed:15205477). Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT) (By similarity). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes (PubMed:18485871). The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus (PubMed:18485871, PubMed:21504832). Deacetylates 'Lys-266' of SUV39H1, leading to its activation (PubMed:21504832). Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 (PubMed:19188449). Deacetylates H2A and 'Lys-26' of H1-4 (PubMed:15469825). Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression (PubMed:20375098). Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting (By similarity). Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1 (PubMed:15469825, PubMed:18004385). Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 (PubMed:18004385, PubMed:21504832). This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response (PubMed:18004385, PubMed:21504832). Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence (PubMed:11672523, PubMed:12006491, PubMed:22542455). Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I (By similarity). Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability (PubMed:19364925, PubMed:21807113). Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation (PubMed:14976264, PubMed:14980222, PubMed:21841822). Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis (PubMed:15126506). Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing (PubMed:21947282). Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF (PubMed:15152190). Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 (PubMed:17283066, PubMed:17620057, PubMed:20100829, PubMed:20620956). Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver (PubMed:15692560). Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation (PubMed:16892051). Involved in HES1- and HEY2-mediated transcriptional repression (PubMed:12535671). In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' (PubMed:21698133). Deacetylates MEF2D (PubMed:16166628). Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 (PubMed:17505061). Represses HNF1A-mediated transcription (By similarity). Required for the repression of ESRRG by CREBZF (PubMed:19690166). Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed (PubMed:17936707). Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis (PubMed:20817729, PubMed:29765047). Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2 (By similarity). Deacetylates p300/EP300 and PRMT1 (By similarity). Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation (PubMed:21701047). Involved in liver and muscle metabolism. Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis (PubMed:23142079). Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression (PubMed:17290224, PubMed:20817729). Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2 (PubMed:15205477, PubMed:16998810, PubMed:17334224, PubMed:17612497, PubMed:20670893, PubMed:21149730). Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN (PubMed:15205477, PubMed:17334224, PubMed:20097625). Promotes DNA double-strand breaks by mediating deacetylation of SIRT6 (PubMed:32538779). Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage (PubMed:18203716). Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 (PubMed:19934257). Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER) (PubMed:32034146). Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8 (PubMed:18296641). Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation (PubMed:21775285). Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear (PubMed:18687677, PubMed:20203304). In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability (PubMed:21890893). Deacetylates MECOM/EVI1 (PubMed:21555002). Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization (PubMed:22274616). During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling (PubMed:18662546). Deacetylates BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator (By similarity). Deacetylates PER2, facilitating its ubiquitination and degradation by the proteasome (By similarity). Protects cardiomyocytes against palmitate-induced apoptosis (By similarity). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (PubMed:20955178). Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis (PubMed:30193097). Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 (PubMed:24415752). Deacetylates CTNB1 at 'Lys-49' (PubMed:24824780). In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (By similarity). Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity (By similarity). Involved in the regulation of centrosome duplication: deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly (PubMed:31722219). Deacetylates NDC80/HEC1 (PubMed:30409912). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating protein delactylation, depropionylation and decrotonylation (PubMed:28497810, PubMed:38512451). Mediates depropionylation of Osterix (SP7) (By similarity). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase (PubMed:28497810). Mediates protein delactylation of TEAD1 and YAP1 (PubMed:38512451)\n Location: Nucleus, PML body\n Domains: Deacetylase sirtuin-type\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1029779, "gene_symbol_1": "ATP6V1B1", "gene_symbol_2": "SIRT1", "detection_method": null, "compartment_type": "different", "uniprot_1": "P15313", "uniprot_2": "Q96EB6"}} +{"question_id": "PPIL3-0191", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: POLE3 (Q9NRF9, 147 AA)\n Function: Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity). Forms a complex with CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1 (PubMed:10801849). Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex (PubMed:14759371)\n Location: Nucleus\n Domains: None\n\nProtein 2: LAMTOR3 (Q9UHA4, 124 AA)\n Function: As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:20381137, PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492, PubMed:30181260). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492, PubMed:30181260). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492, PubMed:30181260). Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2 (By similarity)\n Location: Late endosome membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 925790, "gene_symbol_1": "POLE3", "gene_symbol_2": "LAMTOR3", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9NRF9", "uniprot_2": "Q9UHA4"}} +{"question_id": "PPIL3-0192", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: FCHSD2 (O94868, 740 AA)\n Function: Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor (PubMed:29887380). Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling (PubMed:30249660). Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits (PubMed:29887380). Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate (PubMed:29887380). When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex. Does not promote actin polymerisation in the absence of membranes (PubMed:29887380)\n Location: Cytoplasm\n Domains: F-BAR; SH3 1; SH3 2\n\nProtein 2: DCLK2 (Q8N568, 766 AA)\n Function: Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity)\n Location: Cytoplasm, cytoskeleton\n Domains: Doublecortin 1; Doublecortin 2; Protein kinase\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "same", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 99884, "gene_symbol_1": "FCHSD2", "gene_symbol_2": "DCLK2", "detection_method": null, "compartment_type": "same", "uniprot_1": "O94868", "uniprot_2": "Q8N568"}} +{"question_id": "PPIL3-0193", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: BCL2L1 (Q07817, 233 AA)\n Function: Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis\n Location: Mitochondrion inner membrane\n Domains: None\n\nProtein 2: CREBZF (Q9NS37, 354 AA)\n Function: Strongly activates transcription when bound to HCFC1. Suppresses the expression of HSV proteins in cells infected with the virus in a HCFC1-dependent manner. Also suppresses the HCFC1-dependent transcriptional activation by CREB3 and reduces the amount of CREB3 in the cell. Able to down-regulate expression of some cellular genes in CREBZF-expressing cells\n Location: Nucleus\n Domains: bZIP\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1040845, "gene_symbol_1": "BCL2L1", "gene_symbol_2": "CREBZF", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q07817", "uniprot_2": "Q9NS37"}} +{"question_id": "PPIL3-0194", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: AP4B1 (Q9Y6B7, 739 AA)\n Function: Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable)\n Location: Golgi apparatus, trans-Golgi network membrane\n Domains: None\n\nProtein 2: SPTLC1 (O15269, 473 AA)\n Function: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity)\n Location: Endoplasmic reticulum membrane\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1020452, "gene_symbol_1": "AP4B1", "gene_symbol_2": "SPTLC1", "detection_method": null, "compartment_type": "same", "uniprot_1": "Q9Y6B7", "uniprot_2": "O15269"}} +{"question_id": "PPIL3-0195", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: APH1B (Q8WW43, 257 AA)\n Function: Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A\n Location: Membrane\n Domains: None\n\nProtein 2: OTUB1 (Q96FW1, 271 AA)\n Function: Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation (PubMed:12401499, PubMed:12704427, PubMed:14661020, PubMed:23827681). Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen (PubMed:14661020). Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy (PubMed:14661020). Isoform 1 destabilizes RNF128, leading to prevent anergy (PubMed:14661020). In contrast, isoform 2 stabilizes RNF128 and promotes anergy (PubMed:14661020). Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128 (PubMed:14661020). Deubiquitinates estrogen receptor alpha (ESR1) (PubMed:19383985). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains (PubMed:18954305, PubMed:19211026, PubMed:23827681). Not able to cleave di-ubiquitin (PubMed:18954305, PubMed:23827681). Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (PubMed:18954305, PubMed:23827681)\n Location: Cytoplasm\n Domains: OTU\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 441479, "gene_symbol_1": "APH1B", "gene_symbol_2": "OTUB1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q8WW43", "uniprot_2": "Q96FW1"}} +{"question_id": "PPIL3-0196", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: LSM6 (P62312, 80 AA)\n Function: Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320). Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner, facilitating the efficient association of RNA processing factors with their substrates. Component of the cytoplasmic LSM1-LSM7 complex, which is thought to be involved in mRNA degradation by activating the decapping step in the 5'-to-3' mRNA decay pathway (Probable)\n Location: Cytoplasm\n Domains: Sm\n\nProtein 2: CDC16 (Q13042, 620 AA)\n Function: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132)\n Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 1225129, "gene_symbol_1": "LSM6", "gene_symbol_2": "CDC16", "detection_method": null, "compartment_type": "same", "uniprot_1": "P62312", "uniprot_2": "Q13042"}} +{"question_id": "PPIL3-0197", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: ATF4 (P18848, 351 AA)\n Function: Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:16682973, PubMed:17684156, PubMed:31023583, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:31023583, PubMed:32132707). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:31023583, PubMed:32132706, PubMed:32132707). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Activates the expression of COX7A2L/SCAF1 downstream of the EIF2AK3/PERK-mediated unfolded protein response, thereby promoting formation of respiratory chain supercomplexes and increasing mitochondrial oxidative phosphorylation (PubMed:31023583). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988). May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (PubMed:33384352). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471)\n Location: Nucleus\n Domains: bZIP\n\nProtein 2: BOP1 (Q14137, 746 AA)\n Function: Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome\n Location: Nucleus, nucleolus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "same", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 648930, "gene_symbol_1": "ATF4", "gene_symbol_2": "BOP1", "detection_method": null, "compartment_type": "same", "uniprot_1": "P18848", "uniprot_2": "Q14137"}} +{"question_id": "PPIL3-0198", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: NOSIP (Q9Y314, 301 AA)\n Function: E3 ubiquitin-protein ligase that is essential for proper development of the forebrain, the eye, and the face. Catalyzes monoubiquitination of serine/threonine-protein phosphatase 2A (PP2A) catalytic subunit PPP2CA/PPP2CB (By similarity). Negatively regulates nitric oxide production by inducing NOS1 and NOS3 translocation to actin cytoskeleton and inhibiting their enzymatic activity (PubMed:11149895, PubMed:15548660, PubMed:16135813)\n Location: Cytoplasm\n Domains: None\n\nProtein 2: UTP11 (Q9Y3A2, 253 AA)\n Function: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA\n Location: Nucleus, nucleolus\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "huri", "gold_category": "different", "metadata": {"source_db": "huri", "confidence_tier": "gold", "result_id": 500436, "gene_symbol_1": "NOSIP", "gene_symbol_2": "UTP11", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q9Y314", "uniprot_2": "Q9Y3A2"}} +{"question_id": "PPIL3-0199", "task": "ppi-l3", "split": "test", "difficulty": "medium", "context_text": "Protein 1: CCNL2 (Q96S94, 520 AA)\n Function: Regulatory component of the cyclin-L-CDK11 complex that regulates transcription and pre-mRNA splicing (PubMed:14684736, PubMed:18216018, PubMed:36104565, PubMed:38059508). May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors (PubMed:14684736)\n Location: Nucleus speckle\n Domains: None\n\nProtein 2: CCNB1 (P14635, 433 AA)\n Function: Essential for the control of the cell cycle at the G2/M (mitosis) transition\n Location: Cytoplasm\n Domains: None\n\nExperimental evidence: experimental assay confirmed no physical interaction.", "gold_answer": "humap", "gold_category": "different", "metadata": {"source_db": "humap", "confidence_tier": "silver", "result_id": 621276, "gene_symbol_1": "CCNL2", "gene_symbol_2": "CCNB1", "detection_method": null, "compartment_type": "different", "uniprot_1": "Q96S94", "uniprot_2": "P14635"}}