ID:NCOA3_HUMAN DESCRIPTION: RecName: Full=Nuclear receptor coactivator 3; Short=NCoA-3; EC=2.3.1.48; AltName: Full=ACTR; AltName: Full=Amplified in breast cancer 1 protein; Short=AIB-1; AltName: Full=CBP-interacting protein; Short=pCIP; AltName: Full=Class E basic helix-loop-helix protein 42; Short=bHLHe42; AltName: Full=Receptor-associated coactivator 3; Short=RAC-3; AltName: Full=Steroid receptor coactivator protein 3; Short=SRC-3; AltName: Full=Thyroid hormone receptor activator molecule 1; Short=TRAM-1; FUNCTION: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. Interacts with PSMB9. CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl- [histone]. ENZYME REGULATION: Coactivator activity on nuclear receptors and NF-kappa-B pathways is enhanced by various hormones, and the TNF cytokine, respectively. TNF stimulation probably enhances phosphorylation, which in turn activates coactivator function. In contrast, acetylation by CREBBP apparently suppresses coactivation of target genes by disrupting its association with nuclear receptors. Binds to CSNK1D. SUBUNIT: Interacts with CARM1 (By similarity). Present in a complex containing NCOA2, IKKA, IKKB, IKBKG and the histone acetyltransferase protein CREBBP. Interacts with CASP8AP2, NR3C1 and PCAF. Interacts with ATAD2 and this interaction is enhanced by estradiol. Found in a complex containing NCOA3, AR and MAK. Interacts with DDX5. INTERACTION: Q92841:DDX17; NbExp=2; IntAct=EBI-81196, EBI-746012; P03372:ESR1; NbExp=2; IntAct=EBI-81196, EBI-78473; O14920:IKBKB; NbExp=3; IntAct=EBI-81196, EBI-81266; P61289:PSME3; NbExp=5; IntAct=EBI-81196, EBI-355546; O43791:SPOP; NbExp=6; IntAct=EBI-81196, EBI-743549; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Mainly cytoplasmic and weakly nuclear. Upon TNF activation and subsequent phosphorylation, it translocates from the cytoplasm to the nucleus. TISSUE SPECIFICITY: Widely expressed. High expression in heart, skeletal muscle, pancreas and placenta. Low expression in brain, and very low in lung, liver and kidney. DOMAIN: Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs 1 and 2 are essential for the association with nuclear receptors, and constitute the RID domain (Receptor-interacting domain). PTM: Acetylated by CREBBP. Acetylation occurs in the RID domain, and disrupts the interaction with nuclear receptors and regulates its function. PTM: Methylated by CARM1 (By similarity). PTM: Phosphorylated by IKK complex. Regulated its function. Phosphorylation at Ser-601 by CK1 promotes coactivator function. POLYMORPHISM: The length of the poly-Gln region is polymorphic in the normal population. MISCELLANEOUS: NCOA3 is frequently amplified or overexpressed in breast and ovarian cancers. 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. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NCOA3ID505ch20q13.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ncoa3/";
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.
Pfam Domains: PF00989 - PAS fold PF07469 - Domain of unknown function (DUF1518) PF08815 - Nuclear receptor coactivator PF08832 - Steroid receptor coactivator PF13426 - PAS domain PF14598 - PAS domain PF16279 - Domain of unknown function (DUF4927) PF16665 - Unstructured region on nuclear receptor coactivator protein
ModBase Predicted Comparative 3D Structure on Q9Y6Q9
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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.
U80737 - Homo sapiens CAGH16 mRNA, complete cds. BC092516 - Homo sapiens nuclear receptor coactivator 3, mRNA (cDNA clone MGC:104986 IMAGE:3064877), complete cds. AK308346 - Homo sapiens cDNA, FLJ98294. AK289683 - Homo sapiens cDNA FLJ77005 complete cds, highly similar to Homo sapiens nuclear receptor coactivator 3 (NCOA3), transcript variant 1, mRNA. AF012108 - Homo sapiens Amplified in Breast Cancer (AIB1) mRNA, complete cds. AB209863 - Homo sapiens mRNA for nuclear receptor coactivator 3 isoform a variant protein. AF016031 - Homo sapiens thyroid hormone receptor activator molecule (TRAM-1) mRNA, complete cds. AF036892 - Homo sapiens nuclear receptor coactivator (ACTR) mRNA, complete cds. BC119001 - Homo sapiens nuclear receptor coactivator 3, mRNA (cDNA clone MGC:141849 IMAGE:40083362), complete cds. BC122547 - Homo sapiens nuclear receptor coactivator 3, mRNA (cDNA clone MGC:141848 IMAGE:40083361), complete cds. AF010227 - Homo sapiens receptor-associated coactivator 3 (RAC3) mRNA, complete cds. KJ892475 - Synthetic construct Homo sapiens clone ccsbBroadEn_01869 NCOA3 gene, encodes complete protein. KJ904597 - Synthetic construct Homo sapiens clone ccsbBroadEn_13991 NCOA3-like gene, encodes complete protein. AB385115 - Synthetic construct DNA, clone: pF1KB5528, Homo sapiens NCOA3 gene for nuclear receptor coactivator 3, complete cds, without stop codon, in Flexi system. AK302595 - Homo sapiens cDNA FLJ53590 complete cds, highly similar to Nuclear receptor coactivator 3 (EC 2.3.1.48). BC036778 - Homo sapiens, clone IMAGE:5755782, mRNA. AK302588 - Homo sapiens cDNA FLJ52175 complete cds, highly similar to Nuclear receptor coactivator 3 (EC 2.3.1.48). AK296810 - Homo sapiens cDNA FLJ51630 complete cds, highly similar to Nuclear receptor coactivator 3 (EC 2.3.1.48). JD279789 - Sequence 260813 from Patent EP1572962. JD432800 - Sequence 413824 from Patent EP1572962. JD527648 - Sequence 508672 from Patent EP1572962. JD530535 - Sequence 511559 from Patent EP1572962. JD357762 - Sequence 338786 from Patent EP1572962. JD112712 - Sequence 93736 from Patent EP1572962. JD090148 - Sequence 71172 from Patent EP1572962. JD326372 - Sequence 307396 from Patent EP1572962. JD287368 - Sequence 268392 from Patent EP1572962. JD328497 - Sequence 309521 from Patent EP1572962. JD091595 - Sequence 72619 from Patent EP1572962. JD556741 - Sequence 537765 from Patent EP1572962. JD330880 - Sequence 311904 from Patent EP1572962. JD314990 - Sequence 296014 from Patent EP1572962. JD374819 - Sequence 355843 from Patent EP1572962. JD563304 - Sequence 544328 from Patent EP1572962. JD390582 - Sequence 371606 from Patent EP1572962. JD315339 - Sequence 296363 from Patent EP1572962. JD221195 - Sequence 202219 from Patent EP1572962. JD369026 - Sequence 350050 from Patent EP1572962. JD508481 - Sequence 489505 from Patent EP1572962. JD145762 - Sequence 126786 from Patent EP1572962. JD237572 - Sequence 218596 from Patent EP1572962. JD492771 - Sequence 473795 from Patent EP1572962. JD287911 - Sequence 268935 from Patent EP1572962. JD512315 - Sequence 493339 from Patent EP1572962. JD233424 - Sequence 214448 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9Y6Q9 (Reactome details) participates in the following event(s):
R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands R-HSA-5687090 p-S MAPK6 phosphorylates NCOA3 R-HSA-9008258 NCOA3 binds ESR1:estrogen:TFGA gene R-HSA-5687097 p-S857 NCOA3 binds ETV4 R-HSA-9008285 NCOA3 recruits EP300 to ESR1:estrogen:TFGA gene:NCOA3 R-HSA-9023840 HATs and coactivators are recruited to the CTSD gene R-HSA-5687099 p-S857 NCOA3:ETV4 bind MMP2 and MMP10 promoter R-HSA-9023860 Histone acetyltransferases are recruited to the TFF1 gene R-HSA-381340 Transcriptional regulation of white adipocyte differentiation R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-5687128 MAPK6/MAPK4 signaling R-HSA-9018519 Estrogen-dependent gene expression R-HSA-1266738 Developmental Biology R-HSA-5619507 Activation of HOX genes during differentiation R-HSA-5683057 MAPK family signaling cascades R-HSA-8939211 ESR-mediated signaling R-HSA-162582 Signal Transduction R-HSA-9006931 Signaling by Nuclear Receptors
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
