| Comment type | Description |
|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=SRC-1A, SRC1a; IsoId=Q15788-1; Sequence=Displayed; Name=2; Synonyms=SRC-1E, SRC1e; IsoId=Q15788-2; Sequence=VSP_011739; Note=Major form. Contains a domain at its C-terminus (1241-1399) that is able to mediate transactivation.; Name=3; Synonyms=SRC-1 (-Q); IsoId=Q15788-3; Sequence=VSP_011738; |
| Catalytic Activity | Acetyl-CoA + [histone] = CoA + acetyl- [histone]. |
| Disease | Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children. |
| Domain | Contains 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. |
| Domain | The C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity. |
| Function | Nuclear 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 |
| Interaction | P59598:Asxl1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-5743705; P03372:ESR1; NbExp=10; IntAct=EBI-455189, EBI-78473; P19785:Esr1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-346765; Q63ZY3:KANK2; NbExp=4; IntAct=EBI-455189, EBI-2556193; P25799:Nfkb1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-643958; Q13133:NR1H3; NbExp=14; IntAct=EBI-455189, EBI-781356; P06536:Nr3c1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-1187143; Q9BTK6:PAGR1; NbExp=4; IntAct=EBI-455189, EBI-2372223; P28065:PSMB9; NbExp=3; IntAct=EBI-455189, EBI-603300; P10276:RARA; NbExp=3; IntAct=EBI-455189, EBI-413374; P19793:RXRA; NbExp=5; IntAct=EBI-455189, EBI-78598; |
| Ptm | Sumoylated; 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. |
| Ptm | Ubiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites. |
| Sequence Caution | Sequence=AAA64187.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAC50305.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; |
| Similarity | Belongs to the SRC/p160 nuclear receptor coactivator family. |
| Similarity | Contains 1 bHLH (basic helix-loop-helix) domain. |
| Similarity | Contains 1 PAS (PER-ARNT-SIM) domain. |
| Subcellular Location | Nucleus {ECO |
| Subunit | Interacts with the methyltransferase CARM1 (By similarity). Interacts 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 the histone acetyltransferases EP300 and CREBBP. Interacts with PCAF, COPS5, NR3C1 and TTLL5/STAMP. 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 |
| Tissue Specificity | Widely expressed. |
| Web Resource | Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ncoa1/"; |