LMPD Database

LMP004832

UniProt Annotations

Entry Information
Gene Namenuclear receptor coactivator 1
Protein EntryNCOA1_MOUSE
UniProt IDP70365
SpeciesMouse
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=SRC-1A, SRC1a; IsoId=P70365-1; Sequence=Displayed; Name=2; Synonyms=SRC-1E, SRC1e; IsoId=P70365-2; Sequence=VSP_011740; Name=3; IsoId=P70365-3; Sequence=VSP_011741; Note=No experimental confirmation available.; Name=4; IsoId=P70365-4; Sequence=VSP_027855, VSP_027856; Note=No experimental confirmation available.;
Catalytic ActivityAcetyl-CoA + [histone] = CoA + acetyl- [histone].
Disruption PhenotypeMice show partial hormone resistance: target organs such as uterus, prostate, testis and mammary gland exhibiting decreased growth and development in response to steroid hormones. Moreover, such mice are prone to obesity due to reduced energy expenditure. {ECO:0000269|PubMed:9506940}.
DomainContains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 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.
DomainThe C-terminal (1113-1447) part mediates the histone acetyltransferase (HAT) activity. {ECO:0000250}.
FunctionNuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3. {ECO:0000269|PubMed:12507421, ECO:0000269|PubMed:16148126, ECO:0000269|PubMed:8616895, ECO:0000269|PubMed:9506940}.
PtmSumoylated; sumoylation increases its interaction with PGR and prolongs its retention in the nucleus. It does not prevent its ubiquitination and does not exert a clear effect on the stability of the protein (By similarity). {ECO:0000250}.
PtmUbiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites (By similarity). {ECO:0000250}.
SimilarityBelongs to the SRC/p160 nuclear receptor coactivator family. {ECO:0000305}.
SimilarityContains 1 bHLH (basic helix-loop-helix) domain. {ECO:0000255|PROSITE-ProRule:PRU00981}.
SimilarityContains 1 PAS (PER-ARNT-SIM) domain. {ECO:0000255|PROSITE-ProRule:PRU00140}.
Subcellular LocationNucleus {ECO:0000255|PROSITE- ProRule:PRU00981, ECO:0000269|PubMed:8855229}.
SubunitInteracts with NCOA6 and NCOA2. Interacts with the FDL motif of STAT5A and STAT5B. Interacts with the LXXLL motif of STAT6. Interacts with STAT3 following IL-6 stimulation. Interacts with the basal transcription factor GTF2B. Interacts with COPS5, NR3C1, PCAF and TTLL5/STAMP. Interacts with the histone acetyltransferases EP300 and CREBBP, and the methyltransferase CARM1. Interacts with PSMB9. Interacts with UBE2L3; they functionally interact to regulate progesterone receptor transcriptional activity. Interacts with PRMT2 and DDX5. Interacts with ASXL1. Interacts with PRMT6. Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif). Interacts in a ligand- dependent fashion with RXRA. {ECO:0000269|PubMed:10381882, ECO:0000269|PubMed:14757047, ECO:0000269|PubMed:16148126, ECO:0000269|PubMed:8616895, ECO:0000269|PubMed:8855229}.
Tissue SpecificityWidely expressed. {ECO:0000269|PubMed:8855229, ECO:0000269|PubMed:9192892}.