NCOA3 Gene: Function, Expression, Mutations, and Disease Associations | Biomedical Database

NCOA3 (Nuclear Receptor Coactivator 3), also known as AIB1 (Amplified In Breast cancer 1) or SRC-3 (Steroid Receptor Coactivator-3), is a member of the p160 steroid receptor coactivator family. It functions as a transcriptional coactivator for nuclear receptors, including estrogen receptor (ER) and progesterone receptor (PR), as well as other transcription factors. NCOA3 is involved in chromatin remodeling, histone acetylation, and recruitment of additional coactivators. It plays critical roles in cell proliferation, differentiation, and metabolism. Overexpression and gene amplification of NCOA3 are frequently observed in breast and ovarian cancers, contributing to tumor progression and endocrine resistance. NCOA3 also participates in inflammatory signaling and lipid metabolism, linking it to metabolic disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Estrogen signaling pathway

• Progesterone signaling pathway

• Androgen receptor signaling

• Nuclear receptor transcription pathway

• PI3K-Akt signaling pathway (via coactivation)

• Notch signaling (crosstalk)

NCOA3 is a 1420-amino acid protein with a molecular weight of approximately 160 kDa. It contains an N-terminal basic helix-loop-helix-Per/ARNT/Sim (bHLH-PAS) domain, a central nuclear receptor interaction domain with LXXLL motifs, and C-terminal activation domains AD1 and AD2. AD1 recruits histone acetyltransferases such as CBP/p300, while AD2 interacts with protein arginine methyltransferases. NCOA3 undergoes post-translational modifications including phosphorylation, acetylation, and ubiquitination, which regulate its stability and activity. It is predominantly nuclear and acts as a scaffold for transcriptional complexes.