{"gene":"ZMYM4","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":1999,"finding":"ZMYM4 (ZNF262/KIAA0425) was identified as a member of the MYM family of zinc-finger proteins, characterized by tandem repeats of a novel zinc-binding MYM motif, and mapped to chromosome band 1p32-p34.","method":"cDNA cloning, FISH mapping, sequence analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct cloning and mapping in a dedicated study, but functional characterization is minimal; structural inference from sequence only","pmids":["10486218"],"is_preprint":false},{"year":2011,"finding":"ZMYM4 contains a DUF3504 domain derived from domesticated Crypton transposon tyrosine recombinase (YR); phylogenetic and synteny analysis indicate ZMYM4 arose via vertebrate genome duplication from the bilaterian WOC gene, and the DUF3504/MYM domain may mediate protein-DNA or protein-protein interactions.","method":"Phylogenetic analysis, domain architecture comparison, synteny analysis, intron position mapping","journal":"Mobile DNA","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — computational/evolutionary analysis only; no direct biochemical or cell-based experiments on ZMYM4 protein function","pmids":["22011512"],"is_preprint":false},{"year":2014,"finding":"The MYM-type zinc fingers present in ZNF262 (ZMYM4) were identified as SUMO-interacting motifs (SIMs) that bind SUMO-2, with individual MYM zinc fingers functioning as SIMs interacting with the same SUMO-2 surface recognized by the canonical SIM consensus.","method":"SUMO-binding assays, domain truncation analysis, immunofluorescence; established for ZNF198 and ZNF261 directly; ZNF262/ZMYM4 identified as a member by sequence homology within the same study","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Weak — direct binding assays were performed for ZNF261 and ZNF198; ZMYM4/ZNF262 was listed as a MYM-family member with predicted SIM activity but direct biochemical validation of ZMYM4 binding was not explicitly reported in the abstract","pmids":["25133527"],"is_preprint":false},{"year":2020,"finding":"ZMYM4 was identified as a novel B-MYB binding protein; ZMYM4 is highly SUMOylated and its interaction with B-MYB is stimulated upon DNA damage induction. Knockdown of ZMYM4 in HEK293 cells had no obvious effect on the cell cycle.","method":"Affinity purification coupled to mass spectrometry (AP-MS), co-immunoprecipitation, knockdown experiments, cell cycle analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — AP-MS discovery confirmed by Co-IP, SUMOylation demonstrated, DNA damage-stimulated interaction shown; single lab but multiple orthogonal methods","pmids":["32439918"],"is_preprint":false}],"current_model":"ZMYM4 is a MYM-type zinc finger protein whose tandem MYM domains function as SUMO-interacting motifs (SIMs) and whose interaction with the transcription factor B-MYB is stimulated by DNA damage; ZMYM4 itself is highly SUMOylated, but its precise molecular role in the DNA-damage response or transcriptional regulation has not been fully resolved."},"narrative":{"mechanistic_narrative":"ZMYM4 (ZNF262/KIAA0425) is a MYM-type zinc-finger protein whose tandem MYM zinc-binding motifs constitute the defining architectural feature of the MYM protein family [PMID:10486218]. These MYM-type zinc fingers function as SUMO-interacting motifs (SIMs) that engage SUMO-2 through the same surface recognized by the canonical SIM consensus, placing ZMYM4 within SUMO-dependent protein interaction networks [PMID:25133527]. Consistent with this, ZMYM4 is itself highly SUMOylated and was identified as a binding partner of the transcription factor B-MYB, an interaction that is stimulated upon induction of DNA damage [PMID:32439918]. Knockdown of ZMYM4 in HEK293 cells produced no overt cell-cycle phenotype, and beyond its SUMO-interaction capacity and DNA-damage-stimulated B-MYB association, the precise molecular role of ZMYM4 in transcriptional regulation or the DNA-damage response has not been resolved in the available corpus [PMID:32439918].","teleology":[{"year":1999,"claim":"Established ZMYM4 as a distinct gene product and defined its core domain architecture, providing the structural framework for all later functional hypotheses.","evidence":"cDNA cloning, FISH chromosomal mapping, and sequence analysis identifying tandem MYM zinc-binding motifs","pmids":["10486218"],"confidence":"Medium","gaps":["No biochemical or cellular function assigned to the protein or its MYM motifs","Zinc-binding and DNA/protein interaction inferred from sequence only"]},{"year":2011,"claim":"Traced the evolutionary origin of ZMYM4 and proposed that its DUF3504/MYM domain mediates protein-DNA or protein-protein interactions, framing a possible nucleic-acid-associated function.","evidence":"Phylogenetic, synteny, domain-architecture, and intron-position analysis (computational only)","pmids":["22011512"],"confidence":"Low","gaps":["Purely computational; no experimental test of DNA or protein binding by ZMYM4","Functional consequence of the DUF3504 domain in ZMYM4 not demonstrated"]},{"year":2014,"claim":"Assigned a biochemical activity to the MYM zinc fingers by showing they act as SUMO-interacting motifs binding SUMO-2, reframing MYM-family proteins as SUMO readers.","evidence":"SUMO-binding assays and domain truncation; direct binding shown for ZNF198/ZNF261, with ZMYM4/ZNF262 included as a homologous family member","pmids":["25133527"],"confidence":"Low","gaps":["Direct SUMO-2 binding was validated for paralogs, not for ZMYM4 itself","SUMO target and biological context of ZMYM4 SIM activity not defined"]},{"year":2020,"claim":"Connected ZMYM4 to a specific cellular context by identifying it as a SUMOylated B-MYB interactor whose binding is induced by DNA damage, linking its SUMO-related properties to a transcription factor and a stress signal.","evidence":"AP-MS discovery with Co-IP confirmation, SUMOylation analysis, knockdown, and cell-cycle analysis in HEK293 cells","pmids":["32439918"],"confidence":"Medium","gaps":["Functional consequence of the ZMYM4-B-MYB interaction unresolved (no cell-cycle effect on knockdown)","Whether ZMYM4 SUMOylation or SIM activity drives the DNA-damage-stimulated binding not established","Downstream transcriptional or repair outputs not identified"]},{"year":null,"claim":"The precise molecular function of ZMYM4 — whether it acts as a SUMO-dependent scaffold, transcriptional cofactor, or DNA-damage-response component — remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstrated catalytic activity or defined substrate","No structural model of MYM-domain engagement with SUMO or B-MYB","Biological pathway and phenotype of ZMYM4 loss largely uncharacterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MYBL2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5VZL5","full_name":"Zinc finger MYM-type protein 4","aliases":["Zinc finger protein 262"],"length_aa":1548,"mass_kda":172.8,"function":"Plays a role in the regulation of cell morphology and cytoskeletal organization","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q5VZL5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZMYM4","classification":"Not Classified","n_dependent_lines":24,"n_total_lines":1208,"dependency_fraction":0.019867549668874173},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DYNLL2","stoichiometry":10.0},{"gene":"DYNLL1","stoichiometry":4.0},{"gene":"CBX1","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"H2AFZ","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGA1","stoichiometry":0.2},{"gene":"HMGN5","stoichiometry":0.2},{"gene":"NUCKS1","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ZMYM4","total_profiled":1310},"omim":[{"mim_id":"617387","title":"GLUTAMINE-RICH PROTEIN 1; QRICH1","url":"https://www.omim.org/entry/617387"},{"mim_id":"613568","title":"ZINC FINGER, MYM-TYPE 4; ZMYM4","url":"https://www.omim.org/entry/613568"},{"mim_id":"602221","title":"ZINC FINGER, MYM-TYPE 2; ZMYM2","url":"https://www.omim.org/entry/602221"},{"mim_id":"300061","title":"ZINC FINGER, MYM-TYPE 3; ZMYM3","url":"https://www.omim.org/entry/300061"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZMYM4"},"hgnc":{"alias_symbol":["KIAA0425","ZNF198L3","MYM"],"prev_symbol":["ZNF262"]},"alphafold":{"accession":"Q5VZL5","domains":[{"cath_id":"-","chopping":"452-484","consensus_level":"medium","plddt":85.28,"start":452,"end":484},{"cath_id":"-","chopping":"1206-1225_1271-1347","consensus_level":"medium","plddt":92.5925,"start":1206,"end":1347},{"cath_id":"3.90.15","chopping":"1371-1428_1456-1548","consensus_level":"medium","plddt":86.1425,"start":1371,"end":1548}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5VZL5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5VZL5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5VZL5-F1-predicted_aligned_error_v6.png","plddt_mean":58.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZMYM4","jax_strain_url":"https://www.jax.org/strain/search?query=ZMYM4"},"sequence":{"accession":"Q5VZL5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5VZL5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5VZL5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5VZL5"}},"corpus_meta":[{"pmid":"9716603","id":"PMC_9716603","title":"Consistent 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Knockdown of ZMYM4 in HEK293 cells had no obvious effect on the cell cycle.\",\n      \"method\": \"Affinity purification coupled to mass spectrometry (AP-MS), co-immunoprecipitation, knockdown experiments, cell cycle analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — AP-MS discovery confirmed by Co-IP, SUMOylation demonstrated, DNA damage-stimulated interaction shown; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"32439918\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZMYM4 is a MYM-type zinc finger protein whose tandem MYM domains function as SUMO-interacting motifs (SIMs) and whose interaction with the transcription factor B-MYB is stimulated by DNA damage; ZMYM4 itself is highly SUMOylated, but its precise molecular role in the DNA-damage response or transcriptional regulation has not been fully resolved.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZMYM4 (ZNF262/KIAA0425) is a MYM-type zinc-finger protein whose tandem MYM zinc-binding motifs constitute the defining architectural feature of the MYM protein family [#0]. These MYM-type zinc fingers function as SUMO-interacting motifs (SIMs) that engage SUMO-2 through the same surface recognized by the canonical SIM consensus, placing ZMYM4 within SUMO-dependent protein interaction networks [#2]. Consistent with this, ZMYM4 is itself highly SUMOylated and was identified as a binding partner of the transcription factor B-MYB, an interaction that is stimulated upon induction of DNA damage [#3]. Knockdown of ZMYM4 in HEK293 cells produced no overt cell-cycle phenotype, and beyond its SUMO-interaction capacity and DNA-damage-stimulated B-MYB association, the precise molecular role of ZMYM4 in transcriptional regulation or the DNA-damage response has not been resolved in the available corpus [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established ZMYM4 as a distinct gene product and defined its core domain architecture, providing the structural framework for all later functional hypotheses.\",\n      \"evidence\": \"cDNA cloning, FISH chromosomal mapping, and sequence analysis identifying tandem MYM zinc-binding motifs\",\n      \"pmids\": [\"10486218\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical or cellular function assigned to the protein or its MYM motifs\",\n        \"Zinc-binding and DNA/protein interaction inferred from sequence only\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Traced the evolutionary origin of ZMYM4 and proposed that its DUF3504/MYM domain mediates protein-DNA or protein-protein interactions, framing a possible nucleic-acid-associated function.\",\n      \"evidence\": \"Phylogenetic, synteny, domain-architecture, and intron-position analysis (computational only)\",\n      \"pmids\": [\"22011512\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational; no experimental test of DNA or protein binding by ZMYM4\",\n        \"Functional consequence of the DUF3504 domain in ZMYM4 not demonstrated\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Assigned a biochemical activity to the MYM zinc fingers by showing they act as SUMO-interacting motifs binding SUMO-2, reframing MYM-family proteins as SUMO readers.\",\n      \"evidence\": \"SUMO-binding assays and domain truncation; direct binding shown for ZNF198/ZNF261, with ZMYM4/ZNF262 included as a homologous family member\",\n      \"pmids\": [\"25133527\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Direct SUMO-2 binding was validated for paralogs, not for ZMYM4 itself\",\n        \"SUMO target and biological context of ZMYM4 SIM activity not defined\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected ZMYM4 to a specific cellular context by identifying it as a SUMOylated B-MYB interactor whose binding is induced by DNA damage, linking its SUMO-related properties to a transcription factor and a stress signal.\",\n      \"evidence\": \"AP-MS discovery with Co-IP confirmation, SUMOylation analysis, knockdown, and cell-cycle analysis in HEK293 cells\",\n      \"pmids\": [\"32439918\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the ZMYM4-B-MYB interaction unresolved (no cell-cycle effect on knockdown)\",\n        \"Whether ZMYM4 SUMOylation or SIM activity drives the DNA-damage-stimulated binding not established\",\n        \"Downstream transcriptional or repair outputs not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular function of ZMYM4 — whether it acts as a SUMO-dependent scaffold, transcriptional cofactor, or DNA-damage-response component — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstrated catalytic activity or defined substrate\",\n        \"No structural model of MYM-domain engagement with SUMO or B-MYB\",\n        \"Biological pathway and phenotype of ZMYM4 loss largely uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"MYBL2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}