{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q99684","secondaryAccessions":["Q8N564"],"uniProtkbId":"GFI1_HUMAN","entryAudit":{"firstPublicDate":"1999-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2003-08-15","entryVersion":210,"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":{"value":"Zinc finger protein Gfi-1"}},"alternativeNames":[{"fullName":{"value":"Growth factor independent protein 1"}},{"fullName":{"value":"Zinc finger protein 163"}}]},"genes":[{"geneName":{"value":"GFI1"},"synonyms":[{"value":"ZNF163"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P70338"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11060035"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12778173"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16287849"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17197705"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17646546"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18805794"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19026687"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20190815"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20547752"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29651020"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8754800"}],"value":"Transcription repressor essential for hematopoiesis (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Functions in a cell-context and development-specific manner (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16287849). Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development (PubMed:12778173). Inhibits SPI1 transcriptional activity at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (By similarity). Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling (By similarity). Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA (PubMed:20547752). Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth (PubMed:19026687). Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters (PubMed:16287849). Required for the maintenance of inner ear hair cells (By similarity). In addition to its role in transcription, acts as a substrate adapter for PRMT1 in the DNA damage response: facilitates the recognition of TP53BP1 and MRE11 substrates by PRMT1, promoting their methylation and the DNA damage response (PubMed:29651020)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P70338"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11060035"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12874834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16287849"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17197705"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17646546"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18805794"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20190815"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20547752"}],"value":"Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2 (By similarity). Also interacts with HDAC1. Interacts (via the zinc-finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation of H3 (H3K9Me2) and repress expression of target genes. Interacts directly with EHMT2. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly with AJUBA (via ITS LIM domains); the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes and, occurs independently of the SNAG domain. Interacts with SPI1; the interaction inhibits SPI1 transcriptional activity targeted at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (By similarity). Interacts with RUNX1T1; the interaction represses HDAC-mediated transcriptional activity. Interacts with RELA; the interaction occurs on liposaccharide (LPS) stimulation and controls RELA DNA binding activity and regulates endotoxin-mediated TOLL-like receptor inflammatory response. Interacts (via the C-terminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 and CDKN1B promoters and repression of transcription"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"Q13111","geneName":"CHAF1A","intActId":"EBI-1020839"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"Q96KQ7","geneName":"EHMT2","intActId":"EBI-744366"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"Q13547","geneName":"HDAC1","intActId":"EBI-301834"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"Q9NQX1","geneName":"PRDM5","intActId":"EBI-4292031"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"Q04206","geneName":"RELA","intActId":"EBI-73886"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"Q91XC0","geneName":"Ajuba","intActId":"EBI-1565930"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q99684","intActId":"EBI-949368"},"interactantTwo":{"uniProtKBAccession":"P17433","geneName":"Spi1","intActId":"EBI-607588"},"numberOfExperiments":2,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"value":"Colocalizes with PIAS3 and RUNX1T1 in nuclear dots"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11060035"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12874834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18805794"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20547752"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8754800"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20190815"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20547752"}],"value":"Down-regulated by TGFB1"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17197705"}],"value":"Zinc fingers 3, 4 and 5 are required for DNA-binding and for interaction with SPI1"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17646546"}],"value":"Ubiquitinated. Ubiquitination and degradation by the proteasome is inhibited by the ubiquitin ligase, ARIH2"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Neutropenia, severe congenital 2, autosomal dominant","diseaseAccession":"DI-01226","acronym":"SCN2","description":"A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.","diseaseCrossReference":{"database":"MIM","id":"613107"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12778173"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Dominant nonimmune chronic idiopathic neutropenia of adults","diseaseAccession":"DI-01499","acronym":"NI-CINA","description":"Relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients.","diseaseCrossReference":{"database":"MIM","id":"607847"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12778173"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"WEB RESOURCE","resourceName":"GFI1base","resourceUrl":"https://databases.lovd.nl/shared/genes/GFI1","ftp":false,"note":"GFI1 mutation db"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/40706/GFI1","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":422,"modifier":"EXACT"}},"description":"Zinc finger protein Gfi-1","featureId":"PRO_0000047193"},{"type":"Zinc finger","location":{"start":{"value":255,"modifier":"EXACT"},"end":{"value":278,"modifier":"EXACT"}},"description":"C2H2-type 1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":284,"modifier":"EXACT"},"end":{"value":306,"modifier":"EXACT"}},"description":"C2H2-type 2","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":312,"modifier":"EXACT"},"end":{"value":334,"modifier":"EXACT"}},"description":"C2H2-type 3","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":340,"modifier":"EXACT"},"end":{"value":362,"modifier":"EXACT"}},"description":"C2H2-type 4","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":368,"modifier":"EXACT"},"end":{"value":390,"modifier":"EXACT"}},"description":"C2H2-type 5","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":396,"modifier":"EXACT"},"end":{"value":419,"modifier":"EXACT"}},"description":"C2H2-type 6","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":109,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":20,"modifier":"EXACT"}},"description":"SNAG domain","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Region","location":{"start":{"value":140,"modifier":"EXACT"},"end":{"value":257,"modifier":"EXACT"}},"description":"Required for interaction with RELA","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20547752"}]},{"type":"Modified residue","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":20,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q07120"}]},{"type":"Modified residue","location":{"start":{"value":56,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q07120"}]},{"type":"Natural variant","location":{"start":{"value":36,"modifier":"EXACT"},"end":{"value":36,"modifier":"EXACT"}},"description":"in dbSNP:rs34631763","featureCrossReferences":[{"database":"dbSNP","id":"rs34631763"}],"featureId":"VAR_052722","alternativeSequence":{"originalSequence":"S","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":382,"modifier":"EXACT"},"end":{"value":382,"modifier":"EXACT"}},"description":"in SCN2; zero neutrophil count. marked monocytosis and reduced T- and B-lymphocyte number leading to recurrent infectious complications. 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