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NCOA3/SRC3 (nuclear receptor coactivator 3/steroid receptor coactivator 3 (SRC3)) is a 155 kD member of the p160/steroid receptor coactivator family containing a nuclear localization sequence, bHLH, and PAS domain. There are two reported isoforms of this protein. NCOA3/SRC3 is localized mainly in the cytoplasm, with weak nuclear expression. The protein is translocated to the nucleus upon phosphorylation. NCOA3/SRC3 is widely expressed with high expression in the heart, skeletal muscle, pancreas, and placenta and low expression in the brain. NCOA3/SRC3 is expressed at very low levels in the lung, liver, and kidney and overexpressed in breast and ovarian cancers. This protein has histone acetyltransferase activity and functions as a transcriptional coactivator for steroid and nuclear hormone receptors. Phosphorylation by I kappaB kinase enhances coactivator function. Acetylation by CREB-BP disrupts interaction with nuclear receptors. NCOA3/SRC3 forms a multisubunit coactivation complex with NCOA2 IKKA, IKKB, IKBKG and histone acetyltransferase protein CREB binding protein and has also been shown to interact with PCAF.
