{"gene":"C15ORF39","run_date":"2026-06-09T22:02:45","timeline":{"discoveries":[{"year":2022,"finding":"C15orf39 was identified and confirmed as a novel substrate of MAPK1 (ERK2) using proximity labeling (APEX2) combined with phosphorylation enrichment mass spectrometry in HEK293T and HCT116 cells.","method":"Proximity labeling (APEX2-pAPEX) with phosphorylation enrichment and mass spectrometry; kinase ON/OFF conditions","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity labeling plus phospho-enrichment MS with kinase ON/OFF comparison, single lab but two orthogonal enrichment methods; confirmation stated but abstract does not detail mutagenesis or in vitro reconstitution","pmids":["35044772"],"is_preprint":false},{"year":2024,"finding":"C15orf39 physically interacts with the cytoplasmic arginine methyltransferase PRMT2, and this interaction stabilizes IκBα to suppress NF-κB signaling, thereby reducing transcription of inflammatory factors IL-6 and TNFα in human microglia (HMC3 cells).","method":"Co-immunoprecipitation (C15orf39–PRMT2 interaction); overexpression and knockdown with cytokine readouts; NF-κB/IκBα pathway analysis","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP for interaction, gain- and loss-of-function with defined molecular pathway readout (IκBα stabilization, NF-κB activation), single lab","pmids":["38892217"],"is_preprint":false},{"year":2024,"finding":"Under inflammatory conditions, NF-κBp65 activation suppresses C15orf39 promoter activity, creating a negative feedback loop that cancels the C15orf39–PRMT2–IκBα suppressive axis on IL-6 and TNFα expression.","method":"Promoter activation assay with NF-κBp65 manipulation in LPS/IFN-γ-stimulated HMC3 cells","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (promoter assay), limited mechanistic detail in abstract","pmids":["38892217"],"is_preprint":false},{"year":2025,"finding":"C15orf39 promotes gastric cancer cell proliferation, migration, and drug resistance by modulating cell mitosis and cell cycle progression; FOXK2, a transcription factor activated downstream of PI3K/AKT signaling, binds the C15orf39 promoter and positively regulates its expression, defining a PI3K/AKT/FOXK2/C15orf39 axis.","method":"Gain- and loss-of-function studies in gastric cancer cells; chromatin immunoprecipitation or promoter-binding assay for FOXK2; cell proliferation, migration, and cell cycle assays; high-throughput sequencing in PIK3CA/PIK3CB/PIK3CD knockdown cells","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis/pathway placement via KD of three PI3K catalytic subunits plus FOXK2 promoter-binding evidence and functional phenotype readouts, single lab","pmids":["40032127"],"is_preprint":false},{"year":2026,"finding":"In mouse ischemic stroke, PRMT2IP (mouse ortholog 1700017B05Rik / human C15orf39) interacts with PRMT2 and inhibits NF-κB signaling through the PRMT2–IκBα axis, reducing IL-6 and TNFα expression; PRMT2IP overexpression reduced cerebral ischemia injury while PRMT2IP knockout worsened outcomes in mice.","method":"Mouse knockout and overexpression in ischemic stroke model; Co-immunoprecipitation (PRMT2IP–PRMT2); NF-κB/IκBα pathway analysis; Mendelian randomization for causal association","journal":"Brain, behavior, and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal genetic manipulation (KO + OE) with defined pathway mechanism (PRMT2–IκBα–NF-κB), Co-IP interaction, single lab replicating prior in vitro findings","pmids":["41887540"],"is_preprint":false}],"current_model":"C15orf39 (PRMT2IP) is a MAPK1 phosphosubstrate that, under basal conditions, physically interacts with PRMT2 to stabilize IκBα and suppress NF-κB–driven transcription of IL-6 and TNFα; in cancer contexts it acts downstream of a PI3K/AKT/FOXK2 transcriptional axis to promote cell cycle progression, proliferation, and migration, while inflammatory NF-κBp65 activation creates a negative feedback loop by repressing the C15orf39 promoter."},"narrative":{"mechanistic_narrative":"C15ORF39 (PRMT2IP) is a regulatory protein that couples kinase signaling to control of NF-κB–driven inflammation and, in cancer, to cell cycle progression [PMID:38892217, PMID:40032127]. It was first defined biochemically as a phosphosubstrate of the MAPK1/ERK2 kinase [PMID:35044772]. C15ORF39 physically associates with the cytoplasmic arginine methyltransferase PRMT2, and this interaction stabilizes IκBα to suppress NF-κB activation, thereby dampening transcription of the inflammatory cytokines IL-6 and TNFα in microglia [PMID:38892217]; the same PRMT2–IκBα axis operates for the mouse ortholog, where overexpression reduces and knockout worsens cerebral ischemic injury [PMID:41887540]. This suppressive axis is itself under inflammatory control, as activated NF-κBp65 represses the C15ORF39 promoter to form a negative feedback loop [PMID:38892217]. In gastric cancer, C15ORF39 is transcriptionally driven by FOXK2 downstream of PI3K/AKT signaling and promotes proliferation, migration, drug resistance, and cell cycle progression, defining a PI3K/AKT/FOXK2/C15ORF39 axis [PMID:40032127].","teleology":[{"year":2022,"claim":"Established the first molecular handle on C15ORF39 by placing it downstream of a specific kinase, answering whether the uncharacterized protein is a regulated signaling node.","evidence":"APEX2 proximity labeling with phospho-enrichment mass spectrometry under kinase ON/OFF conditions in HEK293T and HCT116 cells","pmids":["35044772"],"confidence":"Medium","gaps":["Phosphosite(s) and functional consequence of MAPK1 phosphorylation not defined","No in vitro kinase reconstitution or phosphosite mutagenesis reported","Downstream effect of phosphorylation on C15ORF39 activity unknown"]},{"year":2024,"claim":"Identified PRMT2 as a physical partner and defined the IκBα–NF-κB suppressive mechanism, answering what cellular pathway C15ORF39 regulates.","evidence":"Co-IP, gain- and loss-of-function with cytokine and IκBα/NF-κB readouts in HMC3 microglia","pmids":["38892217"],"confidence":"Medium","gaps":["Whether C15ORF39 affects PRMT2 catalytic activity is not resolved","Mechanism by which the interaction stabilizes IκBα unknown","Single lab, no reciprocal interaction mapping or structural detail"]},{"year":2024,"claim":"Showed the suppressive axis is feedback-regulated, answering how inflammatory signaling overrides C15ORF39's anti-inflammatory function.","evidence":"Promoter activation assay with NF-κBp65 manipulation in LPS/IFN-γ-stimulated HMC3 cells","pmids":["38892217"],"confidence":"Low","gaps":["Single method (promoter assay), no direct evidence of p65 binding to the C15ORF39 promoter","Endogenous promoter regulatory elements not mapped","Kinetics of the feedback loop not characterized"]},{"year":2025,"claim":"Placed C15ORF39 in an oncogenic transcriptional axis, answering how its expression is driven and what proliferative phenotype it produces in cancer.","evidence":"Gain/loss-of-function, FOXK2 promoter-binding assay, cell cycle/migration assays, and sequencing in PIK3CA/B/D knockdown gastric cancer cells","pmids":["40032127"],"confidence":"Medium","gaps":["Molecular effectors C15ORF39 uses to drive mitosis/cell cycle not identified","Whether the PRMT2/NF-κB axis contributes to the cancer phenotype unclear","FOXK2 direct binding site on the promoter not finely mapped"]},{"year":2026,"claim":"Provided in vivo genetic validation of the PRMT2–IκBα–NF-κB axis in a disease model, answering whether the mechanism has physiological consequence.","evidence":"Mouse knockout and overexpression in ischemic stroke, Co-IP, NF-κB/IκBα analysis, and Mendelian randomization","pmids":["41887540"],"confidence":"Medium","gaps":["Cell-type-specific contribution within the brain not dissected","Whether MAPK1 phosphorylation modulates the protective effect untested","Single lab confirmation of prior in vitro mechanism"]},{"year":null,"claim":"The biochemical activity of C15ORF39 itself — how it stabilizes IκBα, whether MAPK1 phosphorylation gates the PRMT2 interaction, and its molecular role in cell cycle progression — remains undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined enzymatic or structural activity for C15ORF39","Integration of MAPK1, PRMT2/NF-κB, and PI3K/FOXK2 inputs into one model untested","No structural data on the C15ORF39–PRMT2 complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,4]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,3,4]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,4]}],"complexes":[],"partners":["PRMT2","MAPK1","FOXK2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6ZRI6","full_name":"Uncharacterized protein C15orf39","aliases":[],"length_aa":1047,"mass_kda":110.7,"function":"Negatively regulates microglial inflammatory responses (PubMed:38892217). Inhibits NF-kappa-B signaling by interacting with PRMT2, thereby reducing the production of pro-inflammatory cytokines, maintaining a steady-state in microglia and limiting excessive inflammation (PubMed:38892217)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q6ZRI6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/C15ORF39"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/C15ORF39","total_profiled":1310},"omim":[{"mim_id":"621142","title":"CHROMOSOME 15 OPEN READING FRAME 39; C15ORF39","url":"https://www.omim.org/entry/621142"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":58.4},{"tissue":"testis","ntpm":69.4}],"url":"https://www.proteinatlas.org/search/C15ORF39"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q6ZRI6","domains":[{"cath_id":"-","chopping":"761-931","consensus_level":"high","plddt":88.4744,"start":761,"end":931}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRI6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRI6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRI6-F1-predicted_aligned_error_v6.png","plddt_mean":48.41},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=C15ORF39","jax_strain_url":"https://www.jax.org/strain/search?query=C15ORF39"},"sequence":{"accession":"Q6ZRI6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZRI6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZRI6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRI6"}},"corpus_meta":[{"pmid":"35044772","id":"PMC_35044772","title":"Interrogating Kinase-Substrate Relationships with Proximity Labeling and Phosphorylation Enrichment.","date":"2022","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/35044772","citation_count":20,"is_preprint":false},{"pmid":"38892217","id":"PMC_38892217","title":"Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38892217","citation_count":3,"is_preprint":false},{"pmid":"40032127","id":"PMC_40032127","title":"C15orf39, a downstream effector of PI3K/AKT signaling, promotes gastric carcinogenesis and correlates with patient outcomes.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40032127","citation_count":2,"is_preprint":false},{"pmid":"39506873","id":"PMC_39506873","title":"The causal association between COVID-19 and ischemic stroke: a mendelian randomization study.","date":"2024","source":"Virology journal","url":"https://pubmed.ncbi.nlm.nih.gov/39506873","citation_count":2,"is_preprint":false},{"pmid":"41887540","id":"PMC_41887540","title":"Microglial PRMT2IP alleviates ischemia-induced brain injury.","date":"2026","source":"Brain, behavior, and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/41887540","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4777,"output_tokens":1427,"usd":0.017868,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8250,"output_tokens":2376,"usd":0.050325,"stage2_stop_reason":"end_turn"},"total_usd":0.068193,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"C15orf39 was identified and confirmed as a novel substrate of MAPK1 (ERK2) using proximity labeling (APEX2) combined with phosphorylation enrichment mass spectrometry in HEK293T and HCT116 cells.\",\n      \"method\": \"Proximity labeling (APEX2-pAPEX) with phosphorylation enrichment and mass spectrometry; kinase ON/OFF conditions\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labeling plus phospho-enrichment MS with kinase ON/OFF comparison, single lab but two orthogonal enrichment methods; confirmation stated but abstract does not detail mutagenesis or in vitro reconstitution\",\n      \"pmids\": [\"35044772\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"C15orf39 physically interacts with the cytoplasmic arginine methyltransferase PRMT2, and this interaction stabilizes IκBα to suppress NF-κB signaling, thereby reducing transcription of inflammatory factors IL-6 and TNFα in human microglia (HMC3 cells).\",\n      \"method\": \"Co-immunoprecipitation (C15orf39–PRMT2 interaction); overexpression and knockdown with cytokine readouts; NF-κB/IκBα pathway analysis\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP for interaction, gain- and loss-of-function with defined molecular pathway readout (IκBα stabilization, NF-κB activation), single lab\",\n      \"pmids\": [\"38892217\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Under inflammatory conditions, NF-κBp65 activation suppresses C15orf39 promoter activity, creating a negative feedback loop that cancels the C15orf39–PRMT2–IκBα suppressive axis on IL-6 and TNFα expression.\",\n      \"method\": \"Promoter activation assay with NF-κBp65 manipulation in LPS/IFN-γ-stimulated HMC3 cells\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (promoter assay), limited mechanistic detail in abstract\",\n      \"pmids\": [\"38892217\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"C15orf39 promotes gastric cancer cell proliferation, migration, and drug resistance by modulating cell mitosis and cell cycle progression; FOXK2, a transcription factor activated downstream of PI3K/AKT signaling, binds the C15orf39 promoter and positively regulates its expression, defining a PI3K/AKT/FOXK2/C15orf39 axis.\",\n      \"method\": \"Gain- and loss-of-function studies in gastric cancer cells; chromatin immunoprecipitation or promoter-binding assay for FOXK2; cell proliferation, migration, and cell cycle assays; high-throughput sequencing in PIK3CA/PIK3CB/PIK3CD knockdown cells\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis/pathway placement via KD of three PI3K catalytic subunits plus FOXK2 promoter-binding evidence and functional phenotype readouts, single lab\",\n      \"pmids\": [\"40032127\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In mouse ischemic stroke, PRMT2IP (mouse ortholog 1700017B05Rik / human C15orf39) interacts with PRMT2 and inhibits NF-κB signaling through the PRMT2–IκBα axis, reducing IL-6 and TNFα expression; PRMT2IP overexpression reduced cerebral ischemia injury while PRMT2IP knockout worsened outcomes in mice.\",\n      \"method\": \"Mouse knockout and overexpression in ischemic stroke model; Co-immunoprecipitation (PRMT2IP–PRMT2); NF-κB/IκBα pathway analysis; Mendelian randomization for causal association\",\n      \"journal\": \"Brain, behavior, and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal genetic manipulation (KO + OE) with defined pathway mechanism (PRMT2–IκBα–NF-κB), Co-IP interaction, single lab replicating prior in vitro findings\",\n      \"pmids\": [\"41887540\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"C15orf39 (PRMT2IP) is a MAPK1 phosphosubstrate that, under basal conditions, physically interacts with PRMT2 to stabilize IκBα and suppress NF-κB–driven transcription of IL-6 and TNFα; in cancer contexts it acts downstream of a PI3K/AKT/FOXK2 transcriptional axis to promote cell cycle progression, proliferation, and migration, while inflammatory NF-κBp65 activation creates a negative feedback loop by repressing the C15orf39 promoter.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"C15ORF39 (PRMT2IP) is a regulatory protein that couples kinase signaling to control of NF-\\u03baB\\u2013driven inflammation and, in cancer, to cell cycle progression [#1, #3]. It was first defined biochemically as a phosphosubstrate of the MAPK1/ERK2 kinase [#0]. C15ORF39 physically associates with the cytoplasmic arginine methyltransferase PRMT2, and this interaction stabilizes I\\u03baB\\u03b1 to suppress NF-\\u03baB activation, thereby dampening transcription of the inflammatory cytokines IL-6 and TNF\\u03b1 in microglia [#1]; the same PRMT2\\u2013I\\u03baB\\u03b1 axis operates for the mouse ortholog, where overexpression reduces and knockout worsens cerebral ischemic injury [#4]. This suppressive axis is itself under inflammatory control, as activated NF-\\u03baBp65 represses the C15ORF39 promoter to form a negative feedback loop [#2]. In gastric cancer, C15ORF39 is transcriptionally driven by FOXK2 downstream of PI3K/AKT signaling and promotes proliferation, migration, drug resistance, and cell cycle progression, defining a PI3K/AKT/FOXK2/C15ORF39 axis [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Established the first molecular handle on C15ORF39 by placing it downstream of a specific kinase, answering whether the uncharacterized protein is a regulated signaling node.\",\n      \"evidence\": \"APEX2 proximity labeling with phospho-enrichment mass spectrometry under kinase ON/OFF conditions in HEK293T and HCT116 cells\",\n      \"pmids\": [\"35044772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phosphosite(s) and functional consequence of MAPK1 phosphorylation not defined\",\n        \"No in vitro kinase reconstitution or phosphosite mutagenesis reported\",\n        \"Downstream effect of phosphorylation on C15ORF39 activity unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified PRMT2 as a physical partner and defined the I\\u03baB\\u03b1\\u2013NF-\\u03baB suppressive mechanism, answering what cellular pathway C15ORF39 regulates.\",\n      \"evidence\": \"Co-IP, gain- and loss-of-function with cytokine and I\\u03baB\\u03b1/NF-\\u03baB readouts in HMC3 microglia\",\n      \"pmids\": [\"38892217\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether C15ORF39 affects PRMT2 catalytic activity is not resolved\",\n        \"Mechanism by which the interaction stabilizes I\\u03baB\\u03b1 unknown\",\n        \"Single lab, no reciprocal interaction mapping or structural detail\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed the suppressive axis is feedback-regulated, answering how inflammatory signaling overrides C15ORF39's anti-inflammatory function.\",\n      \"evidence\": \"Promoter activation assay with NF-\\u03baBp65 manipulation in LPS/IFN-\\u03b3-stimulated HMC3 cells\",\n      \"pmids\": [\"38892217\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (promoter assay), no direct evidence of p65 binding to the C15ORF39 promoter\",\n        \"Endogenous promoter regulatory elements not mapped\",\n        \"Kinetics of the feedback loop not characterized\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed C15ORF39 in an oncogenic transcriptional axis, answering how its expression is driven and what proliferative phenotype it produces in cancer.\",\n      \"evidence\": \"Gain/loss-of-function, FOXK2 promoter-binding assay, cell cycle/migration assays, and sequencing in PIK3CA/B/D knockdown gastric cancer cells\",\n      \"pmids\": [\"40032127\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular effectors C15ORF39 uses to drive mitosis/cell cycle not identified\",\n        \"Whether the PRMT2/NF-\\u03baB axis contributes to the cancer phenotype unclear\",\n        \"FOXK2 direct binding site on the promoter not finely mapped\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Provided in vivo genetic validation of the PRMT2\\u2013I\\u03baB\\u03b1\\u2013NF-\\u03baB axis in a disease model, answering whether the mechanism has physiological consequence.\",\n      \"evidence\": \"Mouse knockout and overexpression in ischemic stroke, Co-IP, NF-\\u03baB/I\\u03baB\\u03b1 analysis, and Mendelian randomization\",\n      \"pmids\": [\"41887540\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Cell-type-specific contribution within the brain not dissected\",\n        \"Whether MAPK1 phosphorylation modulates the protective effect untested\",\n        \"Single lab confirmation of prior in vitro mechanism\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of C15ORF39 itself \\u2014 how it stabilizes I\\u03baB\\u03b1, whether MAPK1 phosphorylation gates the PRMT2 interaction, and its molecular role in cell cycle progression \\u2014 remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined enzymatic or structural activity for C15ORF39\",\n        \"Integration of MAPK1, PRMT2/NF-\\u03baB, and PI3K/FOXK2 inputs into one model untested\",\n        \"No structural data on the C15ORF39\\u2013PRMT2 complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 3, 4]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PRMT2\", \"MAPK1\", \"FOXK2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}