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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 a) translocation generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 & the C-terminus part of NCOA1 b) the fusion protein acts as a transcriptional activator

Related

nuclear hormone receptor family

General

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

Properties

SIZE: entity length = 1441 aa MW = 157 kD COMPARTMENT: cell nucleus MOTIF: DNA-binding motif SITE: 17-20 helix-loop-helix NAME: helix-loop-helix SITE: 21-81 FOR-BINDING-VIA: helix-loop-helix MOTIF: Ser phosphorylation site {S22} LXXLL motif 1 {46-50} Ser phosphorylation site {S103} PAS domain {109-180} MOTIF: LXXLL motif 2 {112-116} STAT3 interaction {361-567} MOTIF: Ser phosphorylation site {S372} serine-rich region {389-682} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S395} Ser phosphorylation site {S517} Ser phosphorylation site {S569} LXXLL motif 3 {633-637} LXXLL motif 4 {690-694} LXXLL motif 5 {749-753} CREBBP interaction {781-988} MOTIF: breakpoint {867-868} LXXLL motif 6 {913-917} Ser phosphorylation site {S1033} glutamine-rich region {1053-1138} MOTIF: glutamine residue (SEVERAL) Thr phosphorylation site {T1179} Ser phosphorylation site {S1185} LXXLL motif 7 {1435-1439}

Database Correlations

OMIM 602691 UniProt Q15788 PFAM correlations Entrez Gene 8648 Kegg hsa:8648 ENZYME 2.3.1.48

References

  1. UniProt :accession Q15788
  2. SeattleSNPs http://pga.gs.washington.edu/data/ncoa1/
  3. OMIM :accession 602691
  4. Corton JC, Anderson SP, Stauber A. Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators. Annu Rev Pharmacol Toxicol. 2000;40:491-518. Review. PMID: 10836145