Alternative products:Additional isoforms seem to exist ,Catalytic activity:Acetyl-CoA + histone = CoA + acetylhistone. ,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) . ,enzyme 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. ,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. ,miscellaneous:NCOA3 is frequently amplified or overexpressed in breast and ovarian cancers. ,polymorphism:The length of the poly-Gln region is polymorphic in the normal population. ,PTM:Acetylated by CREBBP. Acetylation occurs in the RID domain , and disrupts the interaction with nuclear receptors and regulates its function. ,PTM:Methylated by CARM1. ,PTM:Phosphorylated by IKK complex. Regulated its function. ,similarity:Belongs to the SRC/p160 nuclear receptor coactivator family. ,similarity:Contains 1 basic helix-loop-helix (bHLH) domain. ,similarity:Contains 1 PAS (PER-ARNT-SIM) domain. ,subcellular location:Mainly cytoplasmic and weakly nuclear. Upon TNF activation and subsequent phosphorylation , it translocates from the cytoplasm to the nucleus. ,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. ,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. ,
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