nuclear receptor coactivator 6; amplified in breast cancer protein 3; cancer-amplified transcriptional coactivator ASC-2; activating signal cointegrator 2; ASC-2; peroxisome proliferator-activated receptor-interacting protein; PPAR-interacting protein; PRIP; nuclear receptor-activating protein, 250 kDa; nuclear receptor coactivator RAP250; NRC RAP250; thyroid hormone receptor-binding protein (NCOA6, AIB3, KIAA0181, RAP250, TRBP)

Function

• directly binds nuclear receptors & stimulates hormone-dependent transcriptional activity
• steroids (glucocorticoid receptor, estrogen receptor),
• retinoids (RAR, RXR)
• thyroid hormone receptor
• vitamin D3 receptor
• PPAR
• general coactivator, NOT ONLY nuclear receptor coactivator
• coactivation of the NF-kappa-B pathway
• remodeling of chromatin
• interaction with histone acetyltransferase
• interacts with RNPC2, GTF2A, TBP, NCOA1, CRSP3, RBM14, EP300, CREBBP, NCOA6IP, PRMT2/HRMT1L1
• phosphorylated by PRKDC
• phosphorylation on Ser884 decreases binding to ESR1, ESR2
• component of: ASC2/NCOA6 complex (ASCOM)

Structure

• monomer, homodimer
• contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs
• only motif 1 is essential for the association with nuclear receptors, while adjacent Ser-884 displays selectivity for nuclear receptors

Compartment

nucleus

Expression

• ubiquitous
• highly expressed in brain, prostate, testis, ovary
• weakly expressed in lung, thymus, small intestine

Pathology

• frequently amplified or ovexpressed in colon cancer, breast cancer, lung cancers

More general terms

• nuclear (steroid) receptor coactivator (NRC, SRC, NCoA)
• phosphoprotein

Additional terms

• nuclear hormone receptor family

Component of

• ASC-2/NCOA6 complex (MLL2/MLL3 complex, ASCOM complex)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=23054
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:23054
• OMIM: https://mirror.omim.org/entry/605299
• UniProt: http://www.uniprot.org/uniprot/Q14686.html