UniProt functional annotation for Q9Y6Q9



	UniProt functional annotation for Q9Y6Q9

UniProt code: Q9Y6Q9.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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.

Catalytic activity: Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L- lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; Evidence={ECO:0000269|PubMed:9267036};

Activity regulation: 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. Binds to CSNK1D.

Subunit: Interacts with CARM1 (By similarity). Present in a complex containing NCOA2, IKKA, IKKB, IKBKG and the histone acetyltransferase protein CREBBP. Interacts with CASP8AP2, NR3C1 and PCAF. Interacts with ATAD2 and this interaction is enhanced by estradiol. Found in a complex containing NCOA3, AR and MAK. Interacts with DDX5. Interacts with PSMB9. Interacts with NPAS2. Interacts with NR4A3 (By similarity). 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). {ECO:0000250, ECO:0000250|UniProtKB:O09000, ECO:0000269|PubMed:11094166, ECO:0000269|PubMed:11250900, ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:12917342, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:15698540, ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:16957778, ECO:0000269|PubMed:17998543, ECO:0000269|PubMed:19339517, ECO:0000269|PubMed:9238002, ECO:0000269|PubMed:9252329, ECO:0000269|PubMed:9346901}.

Subcellular location: Cytoplasm. Nucleus. Note=Mainly cytoplasmic and weakly nuclear. Upon TNF activation and subsequent phosphorylation, it translocates from the cytoplasm to the nucleus.

Tissue specificity: Widely expressed. High expression in heart, skeletal muscle, pancreas and placenta. Low expression in brain, and very low in lung, liver and kidney.

Domain: 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).

Ptm: Acetylated by CREBBP. Acetylation occurs in the RID domain, and disrupts the interaction with nuclear receptors and regulates its function. {ECO:0000269|PubMed:10490106}.

Ptm: Methylated by CARM1. {ECO:0000250}.

Ptm: Phosphorylated by IKK complex. Regulated its function. Phosphorylation at Ser-601 by CK1 promotes coactivator function. {ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:19339517}.

Polymorphism: The length of the poly-Gln region is polymorphic in the normal population. {ECO:0000269|PubMed:9727751}.

Miscellaneous: NCOA3 is frequently amplified or overexpressed in breast and ovarian cancers.

Similarity: Belongs to the SRC/p160 nuclear receptor coactivator family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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.


Catalytic activity:		Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L- lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; Evidence={ECO:0000269\|PubMed:9267036};
Activity regulation:		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. Binds to CSNK1D.
Subunit:		Interacts with CARM1 (By similarity). Present in a complex containing NCOA2, IKKA, IKKB, IKBKG and the histone acetyltransferase protein CREBBP. Interacts with CASP8AP2, NR3C1 and PCAF. Interacts with ATAD2 and this interaction is enhanced by estradiol. Found in a complex containing NCOA3, AR and MAK. Interacts with DDX5. Interacts with PSMB9. Interacts with NPAS2. Interacts with NR4A3 (By similarity). 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). {ECO:0000250, ECO:0000250\|UniProtKB:O09000, ECO:0000269\|PubMed:11094166, ECO:0000269\|PubMed:11250900, ECO:0000269\|PubMed:11971985, ECO:0000269\|PubMed:12917342, ECO:0000269\|PubMed:14645221, ECO:0000269\|PubMed:15698540, ECO:0000269\|PubMed:16951154, ECO:0000269\|PubMed:16957778, ECO:0000269\|PubMed:17998543, ECO:0000269\|PubMed:19339517, ECO:0000269\|PubMed:9238002, ECO:0000269\|PubMed:9252329, ECO:0000269\|PubMed:9346901}.
Subcellular location:		Cytoplasm. Nucleus. Note=Mainly cytoplasmic and weakly nuclear. Upon TNF activation and subsequent phosphorylation, it translocates from the cytoplasm to the nucleus.
Tissue specificity:		Widely expressed. High expression in heart, skeletal muscle, pancreas and placenta. Low expression in brain, and very low in lung, liver and kidney.
Domain:		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).
Ptm:		Acetylated by CREBBP. Acetylation occurs in the RID domain, and disrupts the interaction with nuclear receptors and regulates its function. {ECO:0000269\|PubMed:10490106}.
Ptm:		Methylated by CARM1. {ECO:0000250}.
Ptm:		Phosphorylated by IKK complex. Regulated its function. Phosphorylation at Ser-601 by CK1 promotes coactivator function. {ECO:0000269\|PubMed:11971985, ECO:0000269\|PubMed:19339517}.
Polymorphism:		The length of the poly-Gln region is polymorphic in the normal population. {ECO:0000269\|PubMed:9727751}.
Miscellaneous:		NCOA3 is frequently amplified or overexpressed in breast and ovarian cancers.
Similarity:		Belongs to the SRC/p160 nuclear receptor coactivator family. {ECO:0000305}.