{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9Y6Q9","secondaryAccessions":["A4LAZ5","Q0VF45","Q5JYD9","Q5JYE0","Q9BR49","Q9UPC9","Q9UPG4","Q9UPG7"],"uniProtkbId":"NCOA3_HUMAN","entryAudit":{"firstPublicDate":"2002-09-19","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1999-11-01","entryVersion":244,"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":{"value":"Nuclear receptor coactivator 3"},"shortNames":[{"value":"NCoA-3"}],"ecNumbers":[{"value":"2.3.1.48"}]},"alternativeNames":[{"fullName":{"value":"ACTR"}},{"fullName":{"value":"Amplified in breast cancer 1 protein"},"shortNames":[{"value":"AIB-1"}]},{"fullName":{"value":"CBP-interacting protein"},"shortNames":[{"value":"pCIP"}]},{"fullName":{"value":"Class E basic helix-loop-helix protein 42"},"shortNames":[{"value":"bHLHe42"}]},{"fullName":{"value":"Receptor-associated coactivator 3"},"shortNames":[{"value":"RAC-3"}]},{"fullName":{"value":"Steroid receptor coactivator protein 3"},"shortNames":[{"value":"SRC-3"}]},{"fullName":{"value":"Thyroid hormone receptor activator molecule 1"},"shortNames":[{"value":"TRAM-1"}]}]},"genes":[{"geneName":{"value":"NCOA3"},"synonyms":[{"value":"AIB1"},{"value":"BHLHE42"},{"value":"RAC3"},{"value":"TRAM1"}]}],"comments":[{"texts":[{"value":"Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:45948"},{"database":"Rhea","id":"RHEA-COMP:9752"},{"database":"Rhea","id":"RHEA-COMP:10731"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29969"},{"database":"ChEBI","id":"CHEBI:57287"},{"database":"ChEBI","id":"CHEBI:57288"},{"database":"ChEBI","id":"CHEBI:61930"}],"ecNumber":"2.3.1.48","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9267036"}]}},{"texts":[{"value":"Coactivator activity on nuclear receptors and NF-kappa-B pathways is enhanced by various hormones, and the TNF cytokine, respectively. TNF stimulation probably enhances phosphorylation, which in turn activates coactivator function. In contrast, acetylation by CREBBP apparently suppresses coactivation of target genes by disrupting its association with nuclear receptors"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O09000"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11094166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11971985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12917342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14645221"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15698540"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16951154"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16957778"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17998543"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9238002"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9252329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9346901"}],"value":"Present in a complex containing NCOA2, IKKA, IKKB, IKBKG and the histone acetyltransferase protein CREBBP (PubMed:11971985, PubMed:9346901). Found in a complex containing NCOA3, AR and MAK (PubMed:16951154). Interacts with ATAD2; the interaction is enhanced by estradiol (PubMed:17998543). Interacts with CARM1 (By similarity). Interacts with CASP8AP2 (PubMed:15698540). Interacts with ESR (PubMed:9238002, PubMed:9252329, PubMed:9346901). Interacts with ESRRB; mediates the interaction between ESRRB and RNA polymerase II complexes and allows NCOA3 corecruitment to ESRRB, KLF4, NANOG, and SOX2 enhancer regions to trigger ESRRB-dependent gene activation involved in self-renewal and pluripotency (By similarity). Interacts with NFKB1 (PubMed:11094166). Interacts with NPAS2 (PubMed:14645221). Interacts with NR3C1 (PubMed:12917342). Interacts with NR4A1/Nur77 (PubMed:18690216). Interacts with NR4A3 (By similarity). Interacts with PCAF (PubMed:9346901). Interacts with PPARA (PubMed:9238002). Interacts with PSMB9 (PubMed:16957778). Interacts with RARA (PubMed:9238002, PubMed:9346901). Interacts with RXRA (PubMed:9238002, PubMed:9346901). Interacts with THRA (PubMed:9238002, PubMed:9346901). Interacts with VDR (PubMed:9238002)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"Q6PL18","geneName":"ATAD2","intActId":"EBI-6598454"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"Q86X55","geneName":"CARM1","intActId":"EBI-2339854"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"P03372","geneName":"ESR1","intActId":"EBI-78473"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"O14920","geneName":"IKBKB","intActId":"EBI-81266"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"P28065","geneName":"PSMB9","intActId":"EBI-603300"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"P61289","geneName":"PSME3","intActId":"EBI-355546"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"P60484","geneName":"PTEN","intActId":"EBI-696162"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"P10276","geneName":"RARA","intActId":"EBI-413374"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"O43791","geneName":"SPOP","intActId":"EBI-743549"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"Q8VIM5-1","geneName":"Myocd","intActId":"EBI-15626132"},"numberOfExperiments":5,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9","intActId":"EBI-81196"},"interactantTwo":{"uniProtKBAccession":"P48281","geneName":"Vdr","intActId":"EBI-346797"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q9Y6Q9-5","intActId":"EBI-11057583"},"interactantTwo":{"uniProtKBAccession":"Q96CV9","geneName":"OPTN","intActId":"EBI-748974"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"value":"Mainly cytoplasmic and weakly nuclear. 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High expression in heart, skeletal muscle, pancreas and placenta. Low expression in brain, and very low in lung, liver and kidney"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"value":"Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs 1 and 2 are essential for the association with nuclear receptors, and constitute the RID domain (Receptor-interacting domain)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10490106"}],"value":"Acetylated by CREBBP. 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However the paper was retracted because certain images were duplicated, leading to concerns regarding the findings of the manuscript"}],"commentType":"CAUTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19339517"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34718754"}],"value":"Was originally reported to be phosphorylated at Ser-601 by CSNK1D/CK1 (PubMed:19339517). However, the corresponding article has been retracted (PubMed:34718754)"}],"commentType":"CAUTION"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/505/NCOA3","ftp":false}],"features":[{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"22814378"}]},{"type":"Chain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":1424,"modifier":"EXACT"}},"description":"Nuclear receptor coactivator 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