Human Gene NCOA1 (ENST00000288599.9) from GENCODE V44
Description: Homo sapiens nuclear receptor coactivator 1 (NCOA1), transcript variant 2, mRNA. (from RefSeq NM_147223) RefSeq Summary (NM_147223): The protein encoded by this gene acts as a transcriptional coactivator for steroid and nuclear hormone receptors. It is a member of the p160/steroid receptor coactivator (SRC) family and like other family members has histone acetyltransferase activity and contains a nuclear localization signal, as well as bHLH and PAS domains. The product of this gene binds nuclear receptors directly and stimulates the transcriptional activities in a hormone-dependent fashion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000288599.9 Gencode Gene: ENSG00000084676.16 Transcript (Including UTRs) Position: hg38 chr2:24,584,477-24,770,702 Size: 186,226 Total Exon Count: 22 Strand: + Coding Region Position: hg38 chr2:24,658,678-24,768,123 Size: 109,446 Coding Exon Count: 19
ID:NCOA1_HUMAN DESCRIPTION: RecName: Full=Nuclear receptor coactivator 1; Short=NCoA-1; EC=2.3.1.48; AltName: Full=Class E basic helix-loop-helix protein 74; Short=bHLHe74; AltName: Full=Protein Hin-2; AltName: Full=RIP160; AltName: Full=Renal carcinoma antigen NY-REN-52; AltName: Full=Steroid receptor coactivator 1; Short=SRC-1; 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. CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl- [histone]. 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. INTERACTION: P59598:Asxl1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-5743705; P03372:ESR1; NbExp=5; IntAct=EBI-455189, EBI-78473; P19785:Esr1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-346765; P25799:Nfkb1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-643958; P06536:Nr3c1 (xeno); NbExp=2; IntAct=EBI-455189, EBI-1187143; SUBCELLULAR LOCATION: Nucleus (By similarity). TISSUE SPECIFICITY: Widely expressed. DOMAIN: The C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity. 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. 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. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. 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. 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. SEQUENCE CAUTION: Sequence=AAA64187.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAC50305.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ncoa1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15788
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000435 positive regulation of transcription from RNA polymerase II promoter by galactose GO:0002155 regulation of thyroid hormone mediated signaling pathway GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0015721 bile acid and bile salt transport GO:0019216 regulation of lipid metabolic process GO:0030521 androgen receptor signaling pathway GO:0030522 intracellular receptor signaling pathway GO:0032870 cellular response to hormone stimulus GO:0043065 positive regulation of apoptotic process GO:0043967 histone H4 acetylation GO:0045666 positive regulation of neuron differentiation GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0060713 labyrinthine layer morphogenesis GO:1904017 cellular response to Thyroglobulin triiodothyronine GO:2001038 regulation of cellular response to drug GO:2001141 regulation of RNA biosynthetic process
AK226063 - Homo sapiens mRNA for nuclear receptor coactivator 1 isoform 1 variant, clone: aj00045. AK290019 - Homo sapiens cDNA FLJ76652 complete cds, highly similar to Homo sapiens nuclear receptor coactivator 1 (NCOA1), transcript variant 2, mRNA. AJ000881 - Homo sapiens mRNA for steroid receptor coactivator 1a. AJ000882 - Homo sapiens mRNA for steroid receptor coactivator 1e. U59302 - Human steroid receptor coactivator-1 F-SRC-1 mRNA, complete cds. LF209464 - JP 2014500723-A/16967: Polycomb-Associated Non-Coding RNAs. MA445041 - JP 2018138019-A/16967: Polycomb-Associated Non-Coding RNAs. JD428880 - Sequence 409904 from Patent EP1572962. JD503122 - Sequence 484146 from Patent EP1572962. BC111533 - Homo sapiens nuclear receptor coactivator 1, mRNA (cDNA clone MGC:129719 IMAGE:40027438), complete cds. BC111534 - Homo sapiens nuclear receptor coactivator 1, mRNA (cDNA clone MGC:129720 IMAGE:40027439), complete cds. U90661 - Homo sapiens steroid receptor coactivator-1 mRNA, complete cds. BC035976 - Homo sapiens, clone IMAGE:4769500, mRNA. U40396 - Human steroid receptor coactivator (SRC-1) mRNA, complete cds. AF242870 - Synthetic construct SRC1 interaction domain-EYFP fusion protein mRNA, complete cds. AY633656 - Homo sapiens PAX3/NCOA1 fusion protein (PAX3/NCOA1 fusion) mRNA, complete cds. U19179 - Human (Hin-2) mRNA, complete cds. U19177 - Human (Hin-2)/HIV1 promoter region chimeric mRNA, partial cds. JD040914 - Sequence 21938 from Patent EP1572962. JD068019 - Sequence 49043 from Patent EP1572962. JD420626 - Sequence 401650 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ppargPathway - Role of PPAR-gamma Coactivators in Obesity and Thermogenesis h_rarrxrPathway - Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_vdrPathway - Control of Gene Expression by Vitamin D Receptor
Reactome (by CSHL, EBI, and GO)
Protein Q15788 (Reactome details) participates in the following event(s):
US Server
