{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q05066","uniProtkbId":"SRY_HUMAN","entryAudit":{"firstPublicDate":"1994-06-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1994-06-01","entryVersion":234,"sequenceVersion":1},"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:0000303","source":"PubMed","id":"1695712"}],"value":"Sex-determining region Y protein"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12970737"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1695712"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"2247149"}],"value":"Testis-determining factor"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1695712"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:11311"}],"value":"SRY"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12970737"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1695712"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"2247149"}],"value":"TDF"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P36394"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11563911"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11818535"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1425584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15170344"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16762365"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8159753"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8265659"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9525897"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"16414182"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"16996051"}],"value":"Transcriptional regulator that controls a genetic switch in male development (PubMed:11563911). It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (PubMed:16414182, PubMed:16996051). Involved in different aspects of gene regulation including promoter activation or repression (PubMed:9525897). Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' (PubMed:11563911, PubMed:1425584, PubMed:15170344, PubMed:8159753, PubMed:8265659). SRY HMG box recognizes DNA by partial intercalation in the minor groove and promotes DNA bending (PubMed:11563911, PubMed:1425584, PubMed:15170344, PubMed:16762365, PubMed:8159753, PubMed:8265659). Also involved in pre-mRNA splicing (PubMed:11818535). In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12871148"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12970737"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15469996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15746192"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16904257"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9054412"}],"value":"Interacts with CALM, EP300, HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1, SLC9A3R2 and WT1 (PubMed:12871148, PubMed:12970737, PubMed:15297880, PubMed:15469996, PubMed:15746192, PubMed:16904257, PubMed:9054412). The interaction with EP300 modulates its DNA-binding activity. The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form (PubMed:15297880). Interaction with PARP1 impaired its DNA-binding activity (PubMed:16904257)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q05066","intActId":"EBI-464987"},"interactantTwo":{"uniProtKBAccession":"Q15599","geneName":"NHERF2","intActId":"EBI-1149760"},"numberOfExperiments":9,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q05738"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11818535"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15746192"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19349578"}],"value":"Acetylation contributes to its nuclear localization and deacetylation by HDAC3 induces a cytoplasmic delocalization (PubMed:15297880). Colocalizes with SOX6 in speckles (PubMed:11818535). Colocalizes with CAML in the nucleus (PubMed:15746192). Colocalizes in the nucleus with ZNF208 isoform KRAB-O and tyrosine hydroxylase (TH) (By similarity). Nuclear import is facilitated by XPO4, a protein that usually acts as a nuclear export signal receptor (PubMed:19349578)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11818535"}],"value":"Nucleus speckle","id":"SL-0186"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19349578"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15746192"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16762365"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19349578"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28030592"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1425584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8159753"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8265659"}],"value":"DNA binding and bending properties of the HMG domains of human and mouse SRY differ form each other. Human SRY shows more extensive minor groove contacts with DNA and a lower specificity of sequence recognition than mouse SRY"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9525897"}],"value":"Phosphorylated on serine residues by PKA. Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"}],"value":"Acetylation of Lys-136 contributes to its nuclear localization and enhances its interaction with KPNB1. Deacetylated by HDAC3"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16904257"}],"value":"Poly-ADP-ribosylated by PARP1. ADP-ribosylation reduces its DNA-binding activity"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"46,XY sex reversal 1","diseaseAccession":"DI-01682","acronym":"SRXY1","description":"A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal.","diseaseCrossReference":{"database":"MIM","id":"400044"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10670762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10721678"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10843173"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10852465"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11563911"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12107262"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12793612"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1339396"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1415266"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1483689"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1570829"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16762365"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17063144"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2247149"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28030592"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7717397"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7776083"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7985018"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8019555"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8105086"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8353496"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8447323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9450909"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9521592"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9678356"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.42"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.48"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10843173"}],"value":"A 45,X chromosomal aberration involving SRY is found in Turner syndrome, a disease characterized by gonadal dysgenesis with short stature, 'streak gonads', variable abnormalities such as webbing of the neck, cubitus valgus, cardiac defects, low posterior hair line. The phenotype is female"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"46,XX sex reversal 1","diseaseAccession":"DI-02395","acronym":"SRXX1","description":"A condition in which male gonads develop in a genetic female (female to male sex reversal).","diseaseCrossReference":{"database":"MIM","id":"400045"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10602113"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9652903"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the SRY family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Protein Spotlight","resourceUrl":"https://www.proteinspotlight.org/back_issues/080","ftp":false,"note":"The tenuous nature of sex - Issue 80 of March 2007"},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/SRY","ftp":false,"note":"SRY entry"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":204,"modifier":"EXACT"}},"description":"Sex-determining region Y protein","featureId":"PRO_0000048671"},{"type":"DNA binding","location":{"start":{"value":60,"modifier":"EXACT"},"end":{"value":128,"modifier":"EXACT"}},"description":"HMG box","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00267"}]},{"type":"Region","location":{"start":{"value":59,"modifier":"EXACT"},"end":{"value":136,"modifier":"EXACT"}},"description":"Sufficient for interaction with KPNB1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"}]},{"type":"Region","location":{"start":{"value":61,"modifier":"EXACT"},"end":{"value":77,"modifier":"EXACT"}},"description":"Required for nuclear localization","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12764225"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15746192"}]},{"type":"Region","location":{"start":{"value":107,"modifier":"EXACT"},"end":{"value":139,"modifier":"EXACT"}},"description":"Sufficient for interaction with EP300","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"}]},{"type":"Region","location":{"start":{"value":130,"modifier":"EXACT"},"end":{"value":136,"modifier":"EXACT"}},"description":"Required for nuclear localization","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"}]},{"type":"Region","location":{"start":{"value":138,"modifier":"EXACT"},"end":{"value":155,"modifier":"EXACT"}},"description":"Necessary for interaction with ZNF208 isoform KRAB-O","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15469996"}]},{"type":"Region","location":{"start":{"value":175,"modifier":"EXACT"},"end":{"value":204,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":198,"modifier":"EXACT"},"end":{"value":204,"modifier":"EXACT"}},"description":"Necessary for interaction with SLC9A3R2","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9054412"}]},{"type":"Compositional bias","location":{"start":{"value":194,"modifier":"EXACT"},"end":{"value":204,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified residue","location":{"start":{"value":136,"modifier":"EXACT"},"end":{"value":136,"modifier":"EXACT"}},"description":"N6-acetyllysine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15297880"}]},{"type":"Natural variant","location":{"start":{"value":3,"modifier":"EXACT"},"end":{"value":3,"modifier":"EXACT"}},"description":"in SRXY1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17063144"}],"featureId":"VAR_030019","alternativeSequence":{"originalSequence":"S","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":18,"modifier":"EXACT"},"end":{"value":18,"modifier":"EXACT"}},"description":"in SRXY1; 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