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nuclear receptor coactivator 3; NCoA-3; thyroid hormone receptor activator molecule 1; TRAM-1; receptor-associated coactivator 3; RAC-3; amplified in breast cancer 1 protein; AIB-1; steroid receptor coactivator protein 3; SRC-3; CBP-interacting protein; pCIP; ACTR; class E basic helix-loop-helix protein 42; bHLHe42 (NCOA3, AIB1, BHLHE42, RAC3, TRAM1)

Function: - nuclear receptor coactivator - binds nuclear receptors & stimulates the transcriptional activities (hormone-dependent) - role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin - role in coactivation of different nuclear receptors, including a) steroid hormone receptors (GR & ER) b) retinoid receptors (RAR & RXR) c) thyroid hormone receptors (erbA) d) vitamin D3 receptor (VDR) e) prostanoid receptors (PPARs) - histone acetyltransferase activity - role in coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. - interacts with PSMB9 - coactivator activity on nuclear receptors & NF-kappa-B pathways is enhanced by various hormones, & TNF, 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 - acetylated by CREBBP - acetylation occurs in the RID domain, & disrupts interaction with nuclear receptors - methylated by CARM1 (putative) - phosphorylated by IKK complex - interacts with CARM1 (putative) - present in a complex containing NCOA2, IKKA, IKKB, IKBKG & the histone acetyltransferase protein CREBBP - interacts with CASP8AP2, NR3C1 & PCAF - interacts with ATAD2; interaction is enhanced by estradiol Structure: - contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs - motifs 1 & 2 are essential for the association with nuclear receptors, & constitute the RID domain (receptor-interacting domain) - 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: - cytoplasm, nucleus - mainly cytoplasmic & weakly nuclear - upon TNF activation & subsequent phosphorylation, it translocates from the cytoplasm to the nucleus Alternative splicing: - named isoforms=5 - additional isoforms seem to exist Expression: - widely expressed - high expression in heart, skeletal muscle, pancreas & placenta - low expression in brain - very low expression in lung, liver & kidney Polymorphism: - the length of the poly-Gln region is polymorphic in the normal population Pathology: - NCOA3 is frequently amplified or overexpressed in breast cancer & ovarian cancer

Related

nuclear hormone receptor family

General

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

Properties

SIZE: entity length = 1424 aa MW = 155 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: DNA-binding motif SITE: 35-43 helix-loop-helix NAME: helix-loop-helix SITE: 44-80 FOR-BINDING-VIA: helix-loop-helix PAS domain {110-180} Ser phosphorylation site {S214} serine-rich region {505-671} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S551} LXXLL motif 1 {685-689} Ser phosphorylation site {S728} LXXLL motif 2 {738-742} Ser phosphorylation site {S857} Ser phosphorylation site {S867} glutamine-rich region {976-980} MOTIF: glutamine residue (SEVERAL) CREBBP interaction {1023-1093} MOTIF: Ser phosphorylation site {S1042} LXXLL motif 3 {1057-1061} Acetyltransferase {1097-1304} MOTIF: glutamine-rich region {1248-1278} MOTIF: glutamine residue (SEVERAL)

Database Correlations

OMIM 601937 UniProt Q9Y6Q9 PFAM correlations Entrez Gene 8202 Kegg hsa:8202 ENZYME 2.3.1.48

References

  1. UniProt :accession Q9Y6Q9
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/NCOA3ID505ch20q13.html
  3. NIEHS-SNPs http://egp.gs.washington.edu/data/ncoa3/
  4. OMIM :accession 601937