{"gene":"ZNF200","run_date":"2026-04-28T23:00:24","timeline":{"discoveries":[{"year":2007,"finding":"ZNF200 was identified as a novel 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 showed that three of ZNF200's five C2H2 zinc finger domains mediate the interaction. ZNF200 co-localizes with G9a in the nucleoplasm as discrete speckles.","method":"Yeast two-hybrid (GHD bait screen), in vitro binding assay, co-immunoprecipitation from HEK293 cells, GST pull-down with deletion mapping, co-localization by fluorescence microscopy","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP + in vitro pull-down + domain mapping + co-localization, multiple orthogonal methods in a single study","pmids":["17584299"],"is_preprint":false},{"year":1998,"finding":"ZNF200 encodes a Krüppel-type zinc finger protein with five C2H2 zinc finger motifs located on human chromosome 16p13.3, with the coding sequence distributed across four exons. An alternatively spliced form was identified. Tissue expression is highest in testis.","method":"cDNA cloning, Northern blot analysis, intron-exon structure determination by genomic sequencing","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 — direct molecular characterization of gene structure and expression; foundational characterization paper","pmids":["9787081"],"is_preprint":false},{"year":2024,"finding":"ZNF200 interacts with PRMT3 via its C-terminal zinc finger regions binding to the N-terminal zinc finger domain of PRMT3. 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 at histone H4 arginine 3 (H4R3me2a). The evolutionary emergence of ZNF200 in mammals correlates with the conservation of the PRMT3 zinc finger domain.","method":"Yeast two-hybrid screening, co-immunoprecipitation, in vitro GST pull-down, molecular docking, proteasome inhibition assays, nuclear fractionation, H4R3me2a immunoblotting","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including in vitro pull-down with domain mapping, functional proteasomal assay, nuclear translocation with epigenetic readout in single rigorous study","pmids":["39513743"],"is_preprint":false}],"current_model":"ZNF200 is a nuclear zinc finger protein that functions as a binding partner and regulator of chromatin-modifying enzymes: it interacts with the H3K9 methyltransferase G9a through three of its five C2H2 zinc finger domains and co-localizes with G9a in nuclear speckles, and it also binds PRMT3 (via its C-terminal zinc fingers contacting PRMT3's N-terminal zinc finger domain), stabilizes PRMT3 against proteasomal degradation, promotes its nuclear translocation, and thereby increases global H4R3me2a histone marks."},"narrative":{"teleology":[{"year":1998,"claim":"Cloning of ZNF200 established it as a Krüppel-type zinc finger gene with five C2H2 motifs, an alternatively spliced form, and preferential expression in testis, providing the molecular framework for subsequent functional studies.","evidence":"cDNA cloning, Northern blot, and genomic sequencing in human tissues","pmids":["9787081"],"confidence":"Medium","gaps":["No functional role or binding partners identified","Expression data limited to Northern blot without protein-level confirmation"]},{"year":2007,"claim":"Identification of G9a as a direct binding partner of ZNF200 established the first functional link between ZNF200 and histone methylation, with domain mapping showing that three of five zinc fingers mediate the interaction and co-localization placing both proteins in nuclear speckles.","evidence":"Yeast two-hybrid, reciprocal co-immunoprecipitation from HEK293 cells, GST pull-down with deletion mapping, and fluorescence microscopy co-localization","pmids":["17584299"],"confidence":"High","gaps":["Functional consequence of ZNF200–G9a interaction on H3K9 methylation not measured","No loss-of-function experiment to assess whether ZNF200 is required for G9a activity or localization","Endogenous interaction not confirmed with antibodies against native proteins"]},{"year":2024,"claim":"Discovery of ZNF200 as a PRMT3 stabilizer and nuclear escort revealed a second chromatin-modifier partnership: ZNF200 inhibits PRMT3 proteasomal degradation, drives its nuclear accumulation, and thereby elevates global H4R3me2a, broadening ZNF200's role from a single interaction partner to a general adaptor for chromatin-modifying enzymes.","evidence":"Yeast two-hybrid, co-immunoprecipitation, GST pull-down with domain mapping, proteasome inhibition assays, nuclear fractionation, and H4R3me2a immunoblotting","pmids":["39513743"],"confidence":"High","gaps":["Whether ZNF200's interactions with G9a and PRMT3 are simultaneous or mutually exclusive is unknown","In vivo phenotype of ZNF200 loss in model organisms not reported","Genome-wide chromatin targets of ZNF200-dependent methylation changes not mapped"]},{"year":null,"claim":"It remains unknown whether ZNF200 acts as a DNA-binding transcription factor through its zinc fingers, whether its partnerships with G9a and PRMT3 are coordinated to regulate specific genomic loci, and what physiological consequence ZNF200 deficiency has in vivo.","evidence":"","pmids":[],"confidence":"Low","gaps":["No DNA-binding activity or target genes characterized","No knockout or knockdown phenotype in animal models","Potential role in testis where expression is highest remains unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0,2]},{"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":["G9A","PRMT3"],"other_free_text":[]},"mechanistic_narrative":"ZNF200 is a Krüppel-type zinc finger protein containing five C2H2 zinc finger motifs that functions as a nuclear scaffold linking chromatin-modifying enzymes to their substrates. ZNF200 interacts with the H3K9 methyltransferase G9a through three of its zinc finger domains and co-localizes with G9a in nucleoplasmic speckles [PMID:17584299]. ZNF200 also binds PRMT3 via its C-terminal zinc fingers contacting PRMT3's N-terminal zinc finger domain, stabilizes PRMT3 against proteasomal degradation, promotes its nuclear translocation, and thereby increases global H4R3me2a histone marks [PMID:39513743]."},"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":4641,"output_tokens":970,"usd":0.014236},"stage2":{"model":"claude-opus-4-6","input_tokens":4155,"output_tokens":1245,"usd":0.07785},"total_usd":0.092086,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"ZNF200 was identified as a novel 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 showed that three of ZNF200's five C2H2 zinc finger domains mediate the interaction. ZNF200 co-localizes with G9a in the nucleoplasm as discrete speckles.\",\n      \"method\": \"Yeast two-hybrid (GHD bait screen), in vitro binding assay, co-immunoprecipitation from HEK293 cells, GST pull-down with deletion mapping, co-localization by fluorescence microscopy\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP + in vitro pull-down + domain mapping + co-localization, multiple orthogonal methods in a single study\",\n      \"pmids\": [\"17584299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"ZNF200 encodes a Krüppel-type zinc finger protein with five C2H2 zinc finger motifs located on human chromosome 16p13.3, with the coding sequence distributed across four exons. An alternatively spliced form was identified. Tissue expression is highest in testis.\",\n      \"method\": \"cDNA cloning, Northern blot analysis, intron-exon structure determination by genomic sequencing\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct molecular characterization of gene structure and expression; foundational characterization paper\",\n      \"pmids\": [\"9787081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ZNF200 interacts with PRMT3 via its C-terminal zinc finger regions binding to the N-terminal zinc finger domain of PRMT3. 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 at histone H4 arginine 3 (H4R3me2a). The evolutionary emergence of ZNF200 in mammals correlates with the conservation of the PRMT3 zinc finger domain.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, in vitro GST pull-down, molecular docking, proteasome inhibition assays, nuclear fractionation, H4R3me2a immunoblotting\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including in vitro pull-down with domain mapping, functional proteasomal assay, nuclear translocation with epigenetic readout in single rigorous study\",\n      \"pmids\": [\"39513743\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNF200 is a nuclear zinc finger protein that functions as a binding partner and regulator of chromatin-modifying enzymes: it interacts with the H3K9 methyltransferase G9a through three of its five C2H2 zinc finger domains and co-localizes with G9a in nuclear speckles, and it also binds PRMT3 (via its C-terminal zinc fingers contacting PRMT3's N-terminal zinc finger domain), stabilizes PRMT3 against proteasomal degradation, promotes its nuclear translocation, and thereby increases global H4R3me2a histone marks.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ZNF200 is a Krüppel-type zinc finger protein containing five C2H2 zinc finger motifs that functions as a nuclear scaffold linking chromatin-modifying enzymes to their substrates. ZNF200 interacts with the H3K9 methyltransferase G9a through three of its zinc finger domains and co-localizes with G9a in nucleoplasmic speckles [PMID:17584299]. ZNF200 also binds PRMT3 via its C-terminal zinc fingers contacting PRMT3's N-terminal zinc finger domain, stabilizes PRMT3 against proteasomal degradation, promotes its nuclear translocation, and thereby increases global H4R3me2a histone marks [PMID:39513743].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Cloning of ZNF200 established it as a Krüppel-type zinc finger gene with five C2H2 motifs, an alternatively spliced form, and preferential expression in testis, providing the molecular framework for subsequent functional studies.\",\n      \"evidence\": \"cDNA cloning, Northern blot, and genomic sequencing in human tissues\",\n      \"pmids\": [\"9787081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional role or binding partners identified\",\n        \"Expression data limited to Northern blot without protein-level confirmation\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identification of G9a as a direct binding partner of ZNF200 established the first functional link between ZNF200 and histone methylation, with domain mapping showing that three of five zinc fingers mediate the interaction and co-localization placing both proteins in nuclear speckles.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal co-immunoprecipitation from HEK293 cells, GST pull-down with deletion mapping, and fluorescence microscopy co-localization\",\n      \"pmids\": [\"17584299\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Functional consequence of ZNF200–G9a interaction on H3K9 methylation not measured\",\n        \"No loss-of-function experiment to assess whether ZNF200 is required for G9a activity or localization\",\n        \"Endogenous interaction not confirmed with antibodies against native proteins\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Discovery of ZNF200 as a PRMT3 stabilizer and nuclear escort revealed a second chromatin-modifier partnership: ZNF200 inhibits PRMT3 proteasomal degradation, drives its nuclear accumulation, and thereby elevates global H4R3me2a, broadening ZNF200's role from a single interaction partner to a general adaptor for chromatin-modifying enzymes.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, GST pull-down with domain mapping, proteasome inhibition assays, nuclear fractionation, and H4R3me2a immunoblotting\",\n      \"pmids\": [\"39513743\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether ZNF200's interactions with G9a and PRMT3 are simultaneous or mutually exclusive is unknown\",\n        \"In vivo phenotype of ZNF200 loss in model organisms not reported\",\n        \"Genome-wide chromatin targets of ZNF200-dependent methylation changes not mapped\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether ZNF200 acts as a DNA-binding transcription factor through its zinc fingers, whether its partnerships with G9a and PRMT3 are coordinated to regulate specific genomic loci, and what physiological consequence ZNF200 deficiency has in vivo.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No DNA-binding activity or target genes characterized\",\n        \"No knockout or knockdown phenotype in animal models\",\n        \"Potential role in testis where expression is highest remains unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0, 2]},\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\": [\"G9a\", \"PRMT3\"],\n    \"other_free_text\": []\n  }\n}\n```"}