nuclear receptor coactivator 1; NCoA-1; steroid receptor coactivator 1; SRC-1; RIP160; protein Hin-2; renal carcinoma antigen NY-REN-52; class E basic helix-loop-helix protein 74; bHLHe74 (NCOA1, BHLHE74, SRC1)

Function

• nuclear receptor coactivator
• binds nuclear receptors & stimulates the transcriptional activities (hormone-dependent)
• role in coactivation of different nuclear receptors, including steroids receptor (PGR, GR & ER), retinoid receptors (RXRs), thyroid hormone receptors (erbA) & prostanoid receptors (PPAR)
• involved in coactivation mediated by STAT3, STAT5A, STAT5B & STAT6 transcription factors.
• displays histone acetyltransferase activity toward H3 & H4; relevance is unclear
• role in creating multisubunit coactivator complexes that act via remodeling of chromatin, & possibly acts by participating in both chromatin remodeling & recruitment of general transcription factors required with NCOA2 to control energy balance between white & brown adipose tissues
• required for mediating steroid hormone response
• isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 & isoform 3
• sumoylated; sumoylation increases its interaction with PGR & prolongs its retention in the nucleus
• sumoylation does not prevent its ubiquitination & does not exert a clear effect on the stability of the protein
• ubiquitinated; leading to proteasome-mediated degradation
• ubiquitination & sumoylation take place at different sites
• phosphorylated upon DNA damage, probably by ATM or ATR
• interacts with the methyltransferase CARM1
• interacts with NCOA6 & NCOA2.
• interacts with the FDL motif of STAT5A & STAT5B
• interacts with the LXXLL motif of STAT6
• interacts with STAT3 following IL-6 stimulation
• interacts with the basal transcription factor GTF2B
• interacts with the histone acetyltransferases EP300 & CREBBP
• interacts with PCAF, COPS5, NR3C1 & TTLL5/STAMP
• interacts with PSMB9

Structure

• the C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity
• contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs
• LXXLL motifs 3, 4 & 5 are essential for the association with nuclear receptors
• LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro
• belongs to the SRC/p160 nuclear receptor coactivator family
• contains 1 basic helix-loop-helix (bHLH) domain
• contains 1 PAS (PER-ARNT-SIM) domain

Compartment

nucleus (putative)

Alternative splicing

• named isoforms=3
• major form contains a domain at its C-terminus (1241-1399) that is able to mediate transactivation

Expression

widely expressed

Pathology

• chromosomal translocation t(2;2)(q35;p23) involving NCOA1 with PAX3 is a cause of rhabdomyosarcoma
  • translocation generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 & the C-terminus part of NCOA1
  • the fusion protein acts as a transcriptional activator

More general terms

• nuclear (steroid) receptor coactivator (NRC, SRC, NCoA)
• DNA-binding protein
• phosphoprotein
• acetyltransferase

Additional terms

• nuclear hormone receptor family

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8648
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8648
• OMIM: https://mirror.omim.org/entry/602691
• UniProt: http://www.uniprot.org/uniprot/Q15788.html