{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15596","secondaryAccessions":["Q14CD2"],"uniProtkbId":"NCOA2_HUMAN","entryAudit":{"firstPublicDate":"2001-02-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1997-05-01","entryVersion":251,"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":"Nuclear receptor coactivator 2"},"shortNames":[{"value":"NCoA-2"}]},"alternativeNames":[{"fullName":{"value":"Class E basic helix-loop-helix protein 75"},"shortNames":[{"value":"bHLHe75"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"8670870"}],"value":"Transcriptional intermediary factor 2"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"8670870"}],"value":"hTIF2"}]}]},"genes":[{"geneName":{"value":"NCOA2"},"synonyms":[{"value":"BHLHE75"},{"value":"SRC2"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"8670870"}],"value":"TIF2"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61026"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22504882"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23508108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26553876"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8670870"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9430642"}],"value":"Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61026"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10478845"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10594042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11971985"},{"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":"19481530"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21152046"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22504882"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23508108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26553876"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27694446"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31419141"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32631515"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33335203"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35503419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9430642"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9590696"}],"value":"Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP (PubMed:11971985, PubMed:9430642). Present in a complex containing CARM1 and EP300/P300. Interacts (via C-terminus) with CREBBP (PubMed:11971985, PubMed:9430642). Interacts (via LXXLL 1, 2 and 3 motifs) with RORA (via AF-2 motif) (PubMed:10478845). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif). Interacts with APEX1 (PubMed:10594042). Interacts with BMAL1 (By similarity). Interacts with CARM1. Interacts with CASP8AP2. Interacts with CLOCK. Interacts with ESR1 (PubMed:9430642). Interacts with HIF1A (PubMed:10594042). Interacts with NCOA1 (PubMed:10594042). Interacts with NR4A1/Nur77 (PubMed:18690216). Interacts with NR4A3; potentiates the activity of the NR4A3 (By similarity). Interacts with NR1H3 (PubMed:19481530). Interacts with NR3C1 (PubMed:23508108, PubMed:9590696). Interacts with NR3C2. Interacts with PSMB9 (PubMed:16957778). Interacts with RARA (PubMed:21152046, PubMed:9430642). Interacts with RXRA (PubMed:21152046, PubMed:9430642). Interacts with RWDD3 (PubMed:23508108). Interacts with TTLL5/STAMP (PubMed:17116691). Interacts with NR5A2 (PubMed:22504882, PubMed:26553876, PubMed:27694446, PubMed:31419141, PubMed:33335203, PubMed:32631515, PubMed:35503419)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15596","intActId":"EBI-81236"},"interactantTwo":{"uniProtKBAccession":"P10275","geneName":"AR","intActId":"EBI-608057"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15596","intActId":"EBI-81236"},"interactantTwo":{"uniProtKBAccession":"P03372","geneName":"ESR1","intActId":"EBI-78473"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15596","intActId":"EBI-81236"},"interactantTwo":{"uniProtKBAccession":"O00482-1","geneName":"NR5A2","intActId":"EBI-15960777"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15596","intActId":"EBI-81236"},"interactantTwo":{"uniProtKBAccession":"P19793","geneName":"RXRA","intActId":"EBI-78598"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15596","intActId":"EBI-81236"},"interactantTwo":{"uniProtKBAccession":"Q13239","geneName":"SLA","intActId":"EBI-726214"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8670870"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9430642"}],"value":"Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9430642"}],"value":"The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9430642"}],"value":"Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61026"}],"value":"Acetylated. Deacetylation at Lys-780 by SIRT6 stimulates its ability to coactivate PPARA"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12676584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15657427"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9558366"}],"value":"Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation"}]}},{"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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