{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15788","secondaryAccessions":["O00150","O43792","O43793","Q13071","Q13420","Q2T9G5","Q53SX3","Q6GVI5","Q7KYV3"],"uniProtkbId":"NCOA1_HUMAN","entryAudit":{"firstPublicDate":"2004-10-11","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-09-11","entryVersion":223,"sequenceVersion":3},"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 1"},"shortNames":[{"value":"NCoA-1"}],"ecNumbers":[{"value":"2.3.1.48"}]},"alternativeNames":[{"fullName":{"value":"Class E basic helix-loop-helix protein 74"},"shortNames":[{"value":"bHLHe74"}]},{"fullName":{"value":"Protein Hin-2"}},{"fullName":{"value":"RIP160"}},{"fullName":{"value":"Renal carcinoma antigen NY-REN-52"}},{"fullName":{"value":"Steroid receptor coactivator 1"},"shortNames":[{"value":"SRC-1"}]}]},"genes":[{"geneName":{"value":"NCOA1"},"synonyms":[{"value":"BHLHE74"},{"value":"SRC1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10449719"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12954634"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7481822"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9223281"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9223431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9296499"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9427757"}],"value":"Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3"}],"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"}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P70365"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10567404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10594042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10722692"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11698662"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11773079"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11864604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12039952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12138096"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12917342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12954634"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15367689"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16606617"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16957778"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17116691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18690216"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19786558"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20047962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25219498"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28698609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7481822"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8754792"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9296499"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9744270"}],"value":"Interacts with PPARA; the interaction is direct (PubMed:11698662). Interacts with PPARG; the interaction is direct (PubMed:11698662, PubMed:9744270). Interacts with ESRRG; the interaction is direct (PubMed:11864604). Interacts with STAT5A (via FDL motif) (PubMed:12954634). Interacts with STAT5B (via FDL motif) (PubMed:12954634). Interacts with STAT6 (via LXXLL motif) (PubMed:12138096). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif) (By similarity). Interacts with ASXL1 (PubMed:16606617). Interacts with the methyltransferase CARM1 (By similarity). Interacts with COPS5 (PubMed:10722692). Interacts with the histone acetyltransferase CREBBP (By similarity). Interacts with the histone acetyltransferase EP300 (By similarity). Interacts with ESR1 (PubMed:7481822). Interacts with GCCR (PubMed:7481822). Interacts with the basal transcription factor GTF2B (PubMed:8754792). Interacts with NCOA6 (PubMed:10567404). Interacts with NCOA2 (PubMed:10594042). Interacts with NR3C1 (PubMed:12917342). Interacts with NR4A1/Nur77 (PubMed:18690216). Interacts with NR4A3 (By similarity). Interacts with PCAF (PubMed:9296499). Interacts with PGR (PubMed:7481822). Interacts with PRMT2 (PubMed:12039952). Interacts with PRMT6 (PubMed:20047962). Interacts with PSMB9 (PubMed:16957778). Interacts with RXRA, the interaction is ligand-dependent (PubMed:19786558, PubMed:7481822). Interacts with STAT3 following IL-6 stimulation (PubMed:11773079). Interacts with TRA (PubMed:7481822). Interacts with TRIP4 (PubMed:25219498). Interacts with TTLL5/STAMP (PubMed:17116691). Interacts with UBE2L3; they functionally interact to regulate progesterone receptor transcriptional activity (PubMed:15367689). Interacts with VDR 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LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors. LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12529333"}],"value":"Sumoylated; sumoylation increases its interaction with PGR and prolongs its retention in the nucleus. It does not prevent its ubiquitination and does not exert a clear effect on the stability of the protein"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12529333"}],"value":"Ubiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15313887"}],"value":"A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Major form. Contains a domain at its C-terminus (1241-1399) that is able to mediate transactivation"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the SRC/p160 nuclear receptor coactivator family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"11250900"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"25452582"}],"value":"Was previously reported to interact with DDX1. 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