{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15911","secondaryAccessions":["D3DWS8","O15101","Q13719","Q6ZP98"],"uniProtkbId":"ZFHX3_HUMAN","entryAudit":{"firstPublicDate":"2001-10-18","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2006-06-13","entryVersion":226,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Zinc finger homeobox protein 3"}},"alternativeNames":[{"fullName":{"value":"AT motif-binding factor 1"}},{"fullName":{"value":"AT-binding transcription factor 1"}},{"fullName":{"value":"Alpha-fetoprotein enhancer-binding protein"}},{"fullName":{"value":"Zinc finger homeodomain protein 3"},"shortNames":[{"value":"ZFH-3"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"19597492"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:777"}],"value":"ZFHX3"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1719379"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7592926"}],"value":"ATBF1"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:777"}],"value":"C16orf47"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11312261"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17330845"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20599712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20720010"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25105025"}],"value":"Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signaling can repress the transcription of AFP via its interaction with SMAD2/3 (PubMed:25105025). Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain (By similarity). Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression (PubMed:11312261). Down-regulates the MUC5AC promoter in gastric cancer (PubMed:17330845). In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712). Inhibits estrogen receptor (ESR1) function by selectively competing with coactivator NCOA3 for binding to ESR1 in ESR1-positive breast cancer cells (PubMed:20720010)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14715251"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20599712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20720010"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22452784"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23145062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25105025"}],"value":"Interacts with FNBP3 (By similarity). Interacts with ALKBH4 and PIAS3 (PubMed:14715251, PubMed:23145062). Interacts with ESR1 (PubMed:20720010). Interacts with RUNX3 (PubMed:20599712). Interacts with TRIM25 (PubMed:22452784). Interacts with SMAD2 and SMAD3 (PubMed:25105025)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"O14503","geneName":"BHLHE40","intActId":"EBI-711810"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q8NHQ1","geneName":"CEP70","intActId":"EBI-739624"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q9NZN8","geneName":"CNOT2","intActId":"EBI-743033"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q7L5N1","geneName":"COPS6","intActId":"EBI-486838"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q9H6J7-2","geneName":"CSTPP1","intActId":"EBI-13328871"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q05D60","geneName":"DEUP1","intActId":"EBI-748597"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q5JST6","geneName":"EFHC2","intActId":"EBI-2349927"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q08379","geneName":"GOLGA2","intActId":"EBI-618309"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"A6NEM1","geneName":"GOLGA6L9","intActId":"EBI-5916454"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q15323","geneName":"KRT31","intActId":"EBI-948001"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"O76011","geneName":"KRT34","intActId":"EBI-1047093"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q6A162","geneName":"KRT40","intActId":"EBI-10171697"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q03252","geneName":"LMNB2","intActId":"EBI-2830427"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"P35548","geneName":"MSX2","intActId":"EBI-6447480"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q5JR59-3","geneName":"MTUS2","intActId":"EBI-11522433"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q4G0R1","geneName":"PIBF1","intActId":"EBI-14066006"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q9NRD5","geneName":"PICK1","intActId":"EBI-79165"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"P14859-6","geneName":"POU2F1","intActId":"EBI-11526590"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"P78424","geneName":"POU6F2","intActId":"EBI-12029004"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"P57052","geneName":"RBM11","intActId":"EBI-741332"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"Q69YQ0","geneName":"SPECC1L","intActId":"EBI-351113"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"},"interactantTwo":{"uniProtKBAccession":"O75410-7","geneName":"TACC1","intActId":"EBI-12007872"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15911-2","intActId":"EBI-10237226"}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Expressed in nuclear body (NB)-like dots in the nucleus some of which overlap or closely associate with PML body"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20599712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24651376"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20599712"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"A"},"isoformIds":["Q15911-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"B"},"isoformIds":["Q15911-2"],"sequenceIds":["VSP_006825"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17330845"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20599712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20720010"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22452784"}],"value":"Not found in normal gastric mucosa but found in gastric carcinoma cells (at protein level). Expression is higher in ER-positive breast tumors than ER-negative breast tumors (at protein level)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61329"}],"value":"Hyperphosphorylation protects ZFHX3 from calpain/CAPN1-mediated degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22452784"}],"value":"Ubiquitinated, leading to its proteasomal degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24651376"}],"value":"Nuclear localization is essential for its sumoylation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38035881"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38684900"}],"value":"The poly-Gly region is polymorphic due to GGC triplet repeat expansions ranging from 14 to 26 repeats in the general population"}],"commentType":"POLYMORPHISM"},{"commentType":"DISEASE","disease":{"diseaseId":"Atrial fibrillation, familial, 8","diseaseAccession":"DI-06801","acronym":"ATFB8","description":"A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. 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Patient-derived cells have increased ZFHX3 protein levels and show features of abnormal autophagy (PubMed:38684900)"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Epilepsy, idiopathic generalized 20","diseaseAccession":"DI-07149","acronym":"EIG20","description":"An autosomal recessive form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG20 is characterized by onset of partial epilepsy between infancy and teenage years and seizures progression to complex partial epilepsy and secondary generalized tonic-clonic seizures. 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