{"gene":"ZNF200","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":2007,"finding":"ZNF200 was identified as a direct binding partner of histone H3 lysine 9 methyltransferase G9a. The interaction was demonstrated by in vitro binding assays and co-immunoprecipitation from HEK293 cell extracts. GST pull-down assays with deletion derivatives mapped the interaction to a region encompassing three of the five C2H2 zinc finger domains of ZNF200. ZNF200 co-localizes with G9a in the nucleoplasm as discrete speckles.","method":"Yeast two-hybrid (GHD bait), in vitro binding assay, co-immunoprecipitation from HEK293 extracts, GST pull-down with deletion derivatives, co-localization by immunofluorescence","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and GST pull-down with domain mapping in a single lab; interaction region defined but no functional readout of the complex","pmids":["17584299"],"is_preprint":false},{"year":1998,"finding":"ZNF200 encodes a protein with five C2H2-type zinc finger motifs in tandem arrays; the coding region is distributed across four exons on chromosome 16p13.3. Highest expression is in testis, with very low levels in other tissues, established by Northern blot.","method":"cDNA cloning, sequence analysis, intron-exon structure determination, Northern blot analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — structural/genomic characterization by sequencing and Northern blot, replicated in later studies; no functional assay","pmids":["9787081"],"is_preprint":false},{"year":2024,"finding":"ZNF200 interacts with PRMT3 through its C-terminal zinc finger regions binding to the N-terminal zinc finger domain of PRMT3, as shown by yeast two-hybrid screening, co-immunoprecipitation, in vitro pull-down, and molecular docking. ZNF200 stabilizes PRMT3 by inhibiting its proteasomal degradation. As a nuclear-predominant protein, ZNF200 promotes nuclear translocation of PRMT3, leading to a global increase in asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a).","method":"Yeast two-hybrid screening, co-immunoprecipitation, GST pull-down, molecular docking, proteasomal degradation assay, nuclear fractionation, H4R3me2a immunoblot","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Y2H, Co-IP, GST pull-down, fractionation, histone modification readout) in a single lab; no independent replication yet","pmids":["39513743"],"is_preprint":false}],"current_model":"ZNF200 is a nuclear zinc finger protein (five C2H2 domains) that functions as a protein scaffold/regulator: it binds histone H3K9 methyltransferase G9a via three of its zinc finger domains and co-localizes with G9a in nuclear speckles, and it binds PRMT3 via its C-terminal zinc finger regions, stabilizing PRMT3 against proteasomal degradation and promoting its nuclear translocation to drive H4R3me2a histone modifications."},"narrative":{"mechanistic_narrative":"ZNF200 is a nuclear C2H2-type zinc finger protein that acts as a scaffold and regulator of histone-modifying enzymes [PMID:17584299, PMID:39513743]. It binds the H3K9 methyltransferase G9a through a region encompassing three of its five tandem zinc finger domains and co-localizes with G9a as discrete nucleoplasmic speckles [PMID:17584299]. Through its C-terminal zinc finger regions, ZNF200 also binds the N-terminal zinc finger domain of the arginine methyltransferase PRMT3, stabilizing PRMT3 against proteasomal degradation and promoting its nuclear translocation, which drives a global increase in asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a) [PMID:39513743]. The encoding gene comprises five C2H2 zinc finger motifs distributed across four exons on chromosome 16p13.3 and is expressed predominantly in testis [PMID:9787081]. Beyond these protein-protein interactions with G9a and PRMT3, the direct DNA-binding targets and broader physiological role of ZNF200 have not been characterized in the available corpus.","teleology":[{"year":1998,"claim":"The first question was the basic molecular identity of ZNF200, answered by defining it as a tandem C2H2 zinc finger protein with a testis-restricted expression pattern, establishing it as a candidate sequence-specific nucleic-acid- or protein-binding factor.","evidence":"cDNA cloning, intron-exon mapping, and Northern blot across tissues","pmids":["9787081"],"confidence":"Medium","gaps":["No DNA-binding target or biochemical activity identified","Functional role of testis-enriched expression unaddressed"]},{"year":2007,"claim":"The first functional partner was identified, linking ZNF200 to chromatin regulation by showing it binds the H3K9 methyltransferase G9a and co-localizes with it in nuclear speckles, implicating ZNF200 in repressive histone methylation machinery.","evidence":"Yeast two-hybrid, reciprocal Co-IP from HEK293 extracts, GST pull-down domain mapping, and immunofluorescence co-localization","pmids":["17584299"],"confidence":"Medium","gaps":["No functional readout of the ZNF200-G9a complex on chromatin or transcription","Single-lab interaction without independent replication","Whether ZNF200 modulates G9a activity unknown"]},{"year":2024,"claim":"A second enzyme partner established a mechanistic output: ZNF200 binds PRMT3, protects it from proteasomal degradation, and promotes its nuclear import, thereby increasing H4R3me2a — defining ZNF200 as a stabilizing scaffold that channels arginine methyltransferase activity into the nucleus.","evidence":"Yeast two-hybrid screen, Co-IP, GST pull-down, molecular docking, proteasomal degradation assay, nuclear fractionation, and H4R3me2a immunoblot","pmids":["39513743"],"confidence":"Medium","gaps":["No independent replication","Genomic loci where ZNF200-PRMT3-driven H4R3me2a acts not mapped","Functional/phenotypic consequence of altered H4R3me2a not established"]},{"year":null,"claim":"Whether ZNF200's two documented partnerships (G9a and PRMT3) act in a common pathway, and whether its zinc fingers confer sequence-specific DNA binding to direct these enzymes to target loci, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct DNA target identified","Integration of G9a and PRMT3 functions not tested","No in vivo or disease phenotype established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,2]}],"complexes":[],"partners":["EHMT2","PRMT3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P98182","full_name":"Zinc finger protein 200","aliases":[],"length_aa":395,"mass_kda":45.5,"function":"Localizes protein arginine N-methyltransferase PRMT3 to the nucleus","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P98182/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNF200","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ZNF200","total_profiled":1310},"omim":[{"mim_id":"604599","title":"EUCHROMATIC HISTONE-LYSINE N-METHYLTRANSFERASE 2; EHMT2","url":"https://www.omim.org/entry/604599"},{"mim_id":"603436","title":"ZINC FINGER PROTEIN 205; ZNF205","url":"https://www.omim.org/entry/603436"},{"mim_id":"603231","title":"ZINC FINGER PROTEIN 200; ZNF200","url":"https://www.omim.org/entry/603231"},{"mim_id":"602428","title":"HYALURONAN SYNTHASE 3; HAS3","url":"https://www.omim.org/entry/602428"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mitochondria","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":16.8}],"url":"https://www.proteinatlas.org/search/ZNF200"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"P98182","domains":[{"cath_id":"3.30.160,3.30.160","chopping":"363-391","consensus_level":"medium","plddt":81.8576,"start":363,"end":391}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P98182","model_url":"https://alphafold.ebi.ac.uk/files/AF-P98182-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P98182-F1-predicted_aligned_error_v6.png","plddt_mean":49.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNF200","jax_strain_url":"https://www.jax.org/strain/search?query=ZNF200"},"sequence":{"accession":"P98182","fasta_url":"https://rest.uniprot.org/uniprotkb/P98182.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P98182/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P98182"}},"corpus_meta":[{"pmid":"20111712","id":"PMC_20111712","title":"Risk of ovarian cancer and inherited variants in relapse-associated genes.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/20111712","citation_count":35,"is_preprint":false},{"pmid":"17584299","id":"PMC_17584299","title":"Identification of ZNF200 as a novel binding partner of histone H3 methyltransferase G9a.","date":"2007","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/17584299","citation_count":21,"is_preprint":false},{"pmid":"33717105","id":"PMC_33717105","title":"Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps.","date":"2021","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/33717105","citation_count":12,"is_preprint":false},{"pmid":"27478502","id":"PMC_27478502","title":"A balanced chromosomal translocation involving chromosomes 3 and 16 in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome reveals new candidate genes at 3p22.3 and 16p13.3.","date":"2016","source":"Molecular cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/27478502","citation_count":10,"is_preprint":false},{"pmid":"9787081","id":"PMC_9787081","title":"Identification of two Krüppel-related zinc finger genes (ZNF200 and ZNF210) from human chromosome 16p13.3.","date":"1998","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9787081","citation_count":8,"is_preprint":false},{"pmid":"39513743","id":"PMC_39513743","title":"The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation.","date":"2024","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/39513743","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5360,"output_tokens":968,"usd":0.0153,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7440,"output_tokens":1667,"usd":0.039438,"stage2_stop_reason":"end_turn"},"total_usd":0.054738,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"ZNF200 was identified as a direct binding partner of histone H3 lysine 9 methyltransferase G9a. The interaction was demonstrated by in vitro binding assays and co-immunoprecipitation from HEK293 cell extracts. GST pull-down assays with deletion derivatives mapped the interaction to a region encompassing three of the five C2H2 zinc finger domains of ZNF200. ZNF200 co-localizes with G9a in the nucleoplasm as discrete speckles.\",\n      \"method\": \"Yeast two-hybrid (GHD bait), in vitro binding assay, co-immunoprecipitation from HEK293 extracts, GST pull-down with deletion derivatives, co-localization by immunofluorescence\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and GST pull-down with domain mapping in a single lab; interaction region defined but no functional readout of the complex\",\n      \"pmids\": [\"17584299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"ZNF200 encodes a protein with five C2H2-type zinc finger motifs in tandem arrays; the coding region is distributed across four exons on chromosome 16p13.3. Highest expression is in testis, with very low levels in other tissues, established by Northern blot.\",\n      \"method\": \"cDNA cloning, sequence analysis, intron-exon structure determination, Northern blot analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — structural/genomic characterization by sequencing and Northern blot, replicated in later studies; no functional assay\",\n      \"pmids\": [\"9787081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ZNF200 interacts with PRMT3 through its C-terminal zinc finger regions binding to the N-terminal zinc finger domain of PRMT3, as shown by yeast two-hybrid screening, co-immunoprecipitation, in vitro pull-down, and molecular docking. ZNF200 stabilizes PRMT3 by inhibiting its proteasomal degradation. As a nuclear-predominant protein, ZNF200 promotes nuclear translocation of PRMT3, leading to a global increase in asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a).\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, GST pull-down, molecular docking, proteasomal degradation assay, nuclear fractionation, H4R3me2a immunoblot\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Y2H, Co-IP, GST pull-down, fractionation, histone modification readout) in a single lab; no independent replication yet\",\n      \"pmids\": [\"39513743\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNF200 is a nuclear zinc finger protein (five C2H2 domains) that functions as a protein scaffold/regulator: it binds histone H3K9 methyltransferase G9a via three of its zinc finger domains and co-localizes with G9a in nuclear speckles, and it binds PRMT3 via its C-terminal zinc finger regions, stabilizing PRMT3 against proteasomal degradation and promoting its nuclear translocation to drive H4R3me2a histone modifications.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNF200 is a nuclear C2H2-type zinc finger protein that acts as a scaffold and regulator of histone-modifying enzymes [#0, #2]. It binds the H3K9 methyltransferase G9a through a region encompassing three of its five tandem zinc finger domains and co-localizes with G9a as discrete nucleoplasmic speckles [#0]. Through its C-terminal zinc finger regions, ZNF200 also binds the N-terminal zinc finger domain of the arginine methyltransferase PRMT3, stabilizing PRMT3 against proteasomal degradation and promoting its nuclear translocation, which drives a global increase in asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a) [#2]. The encoding gene comprises five C2H2 zinc finger motifs distributed across four exons on chromosome 16p13.3 and is expressed predominantly in testis [#1]. Beyond these protein-protein interactions with G9a and PRMT3, the direct DNA-binding targets and broader physiological role of ZNF200 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"The first question was the basic molecular identity of ZNF200, answered by defining it as a tandem C2H2 zinc finger protein with a testis-restricted expression pattern, establishing it as a candidate sequence-specific nucleic-acid- or protein-binding factor.\",\n      \"evidence\": \"cDNA cloning, intron-exon mapping, and Northern blot across tissues\",\n      \"pmids\": [\"9787081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No DNA-binding target or biochemical activity identified\", \"Functional role of testis-enriched expression unaddressed\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The first functional partner was identified, linking ZNF200 to chromatin regulation by showing it binds the H3K9 methyltransferase G9a and co-localizes with it in nuclear speckles, implicating ZNF200 in repressive histone methylation machinery.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP from HEK293 extracts, GST pull-down domain mapping, and immunofluorescence co-localization\",\n      \"pmids\": [\"17584299\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional readout of the ZNF200-G9a complex on chromatin or transcription\", \"Single-lab interaction without independent replication\", \"Whether ZNF200 modulates G9a activity unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A second enzyme partner established a mechanistic output: ZNF200 binds PRMT3, protects it from proteasomal degradation, and promotes its nuclear import, thereby increasing H4R3me2a — defining ZNF200 as a stabilizing scaffold that channels arginine methyltransferase activity into the nucleus.\",\n      \"evidence\": \"Yeast two-hybrid screen, Co-IP, GST pull-down, molecular docking, proteasomal degradation assay, nuclear fractionation, and H4R3me2a immunoblot\",\n      \"pmids\": [\"39513743\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No independent replication\", \"Genomic loci where ZNF200-PRMT3-driven H4R3me2a acts not mapped\", \"Functional/phenotypic consequence of altered H4R3me2a not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether ZNF200's two documented partnerships (G9a and PRMT3) act in a common pathway, and whether its zinc fingers confer sequence-specific DNA binding to direct these enzymes to target loci, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct DNA target identified\", \"Integration of G9a and PRMT3 functions not tested\", \"No in vivo or disease phenotype established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EHMT2\", \"PRMT3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}