NCOA3
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).
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.
Post-translational modifications
Acetylated by CREBBP. Acetylation occurs in the RID domain, and disrupts the interaction with nuclear receptors and regulates its function.
Methylated by CARM1.
Phosphorylated by IKK complex. Regulated its function. Phosphorylation at Ser-601 by CK1 promotes coactivator function.
Sequence Similarities
Belongs to the SRC/p160 nuclear receptor coactivator family.
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.
Cellular localization
- Cytoplasm
- Nucleus
- Mainly cytoplasmic and weakly nuclear. Upon TNF activation and subsequent phosphorylation, it translocates from the cytoplasm to the nucleus.
Alternative names
AIB1, BHLHE42, RAC3, TRAM1, NCOA3, Nuclear receptor coactivator 3, NCoA-3, ACTR, Amplified in breast cancer 1 protein, CBP-interacting protein, Class E basic helix-loop-helix protein 42, Receptor-associated coactivator 3, Steroid receptor coactivator protein 3, Thyroid hormone receptor activator molecule 1, AIB-1, pCIP, bHLHe42, RAC-3, SRC-3, TRAM-1