Nuclear receptor coactivator protein (NCoA (or SRC for steroid receptor coactivator family members))

Nuclear receptor coactivator proteins (NCoAs) are a family of transcriptional coregulators that interact with ligand-activated nuclear receptors to promote the transcription of target genes[3][5]. The most well-studied group is the p160 coactivator family, comprising NCOA1 (SRC-1), NCOA2 (SRC-2), and NCOA3 (SRC-3)[1][3]. These proteins mediate the recruitment of chromatin-modifying enzymes, facilitate histone acetylation, and enhance DNA accessibility, thus driving gene expression in response to hormones and other signals[2][5]. NCoAs play critical roles in developmental, metabolic, and inflammatory pathways and are implicated in cancer—particularly through gene fusions and overexpression[1]. Their intrinsically disordered regions make them challenging therapeutic targets as they lack defined pockets for small molecules[1]. While not currently targeted by approved drugs, genetic alterations involving NCoAs serve as biomarkers in malignancies, especially certain leukemias and solid tumors[1].

Other names

p160 nuclear receptor coactivatornuclear receptor transcriptional coactivatorsteroid receptor coactivator (SRC-1, SRC-2, SRC-3)NCOA1NCOA2NCOA3

Not directly druggable; mediates transcriptional activation by bridging nuclear receptors and transcriptional machinery, involving histone acetylation and chromatin remodeling[3][5][1]