NCOA3 (Nuclear Receptor Coactivator 3)
2005-04-01 Sarah L Anzick AffiliationCancer Genetics Branch National Human Genome, Research Institute National Institutes of Health 50 South Drive, MSC 8000 Bldg. 50, Rm. 5148 Bethesda, MD 20892-8000, USA
Identity
HGNC
LOCATION
20q13.12
IMAGE
LEGEND
AIB1 (20q12)
LOCUSID
ALIAS
ACTR,AIB-1,AIB1,CAGH16,CTG26,KAT13B,RAC3,SRC-3,SRC3,TNRC14,TNRC16,TRAM-1,bHLHe42,pCIP
FUSION GENES
DNA/RNA
Genomic structure of NCOA3 with NCBI Build 35.1 genomic positions indicated. Black boxes indicate exons. The translational start (*) and stop codons (^) are also shown. UTR, untranslated region.
Description
The human AIB1 gene spans approximately155 kb and has 23 exons. RNA Expression: Highly expressed in placenta, heart, pancreas, muscle, brain, liver, uterus, pituitary, mammary gland, and testis. Lower levels of expression are found in lung and kidney.
Transcription
Transcription is from centromere to telomere. There are two reported transcripts: Isoform a (7935 bp) and isoform b (7923 bp). Isoform b uses an alternate in-frame splice site and lacks exon 3.
Pseudogene
Chromosome 8 (AF010227)
Proteins
Structural features of AIB1. AIB1 contains a basic helix-loop-helix preceding a PAS (Per/Arnt/Sim) region, serine-and threonine-rich regions, and a charged cluster. There is also a glutamine-rich region that contains a polyglutamine tract. The central portion of the protein contains three LXXLL motifs (L=leucine, X=any amino acid) that are critical for interaction with ligand-bound nuclear receptors. An activation domain located C-terminal to the nuclear receptor interaction domain contains three LXXLL motifs that are important for interaction with general transcription cointegrators, CREB binding protein (CBP)/p300. A second transcriptional activation domain is responsible for interaction with histone methyltransferases, coactivator-associated arginine methyltranserase 1 (CARM1) and PRMT1.
Description
A member of the p160/steroid receptor coactivator family. 1424 amino acids. 155 kDa (130 kDa encoded by isoform b).
Expression
Protein expression found in testis, lung, liver, brain, mammary gland, and heart.
Localisation
Mainly cytoplasmic and weakly nuclear. The protein translocates to the nucleus upon TNF activation and phosphorylation.
Function
A transcriptional coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activation. AIB1 interacts with other transcription factors including TP52, NfkB, and ER81. It has intrinsic histone acytyltransferase activity and recruits CREB Binding Protein (CBP)/p300 cointegrators to a multisubunit coactivator complete.
Mutations
Somatic
The gene copy number and expression levels are altered in several cancer types. Overexpression has been found in breast, ovarian, endometrial, gastric, and pancreatic cancers. Amplification of AIB1 in hepatocellular carcinoma is associated with poor prognosis.
Increased numbers of polyglutamine repeats correlate with higher breast cancer risk in BRCA1 and BRCA2 mutation carriers. However, the polymorphic repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population.
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9252329 | 1997 | AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. | Anzick SL et al |
| 9865902 | 1998 | In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity. | Bautista S et al |
| 9267036 | 1997 | Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. | Chen H et al |
| 10027410 | 1999 | Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas. | Ghadimi BM et al |
| 11355743 | 2001 | Gene amplification and expression of the steroid receptor coactivator SRC3 (AIB1) in sporadic breast and endometrial carcinomas. | Glaeser M et al |
| 14747462 | 2004 | Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu. | Goel A et al |
| 11056690 | 2000 | Polymorphic repeat in AIB1 does not alter breast cancer risk. | Haiman CA et al |
| 15448000 | 2004 | Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during progression of pancreatic adenocarcinoma. | Henke RT et al |
| 14648706 | 2004 | Polyglutamine repeat length in the AIB1 gene modifies breast cancer susceptibility in BRCA1 carriers. | Kadouri L et al |
| 10551785 | 1999 | Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53. | Lee SK et al |
| 9488734 | 1998 | The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation. | Li H et al |
| 9238002 | 1997 | RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. | Li H et al |
| 12618500 | 2003 | Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. | Osborne CK et al |
| 11454686 | 2001 | Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. | Rebbeck TR et al |
| 11502741 | 2001 | An isoform of the coactivator AIB1 that increases hormone and growth factor sensitivity is overexpressed in breast cancer. | Reiter R et al |
| 10861496 | 2000 | Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers. | Sakakura C et al |
| 9765300 | 1998 | A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity. | Suen CS et al |
| 9346901 | 1997 | TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1. | Takeshita A et al |
| 9192892 | 1997 | The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. | Torchia J et al |
| 12436441 | 2002 | Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. | Wang Y et al |
| 12417041 | 2002 | Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers. | Watanabe T et al |
| 11094166 | 2000 | RAC-3 is a NF-kappa B coactivator. | Werbajh S et al |
| 15383283 | 2004 | Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling pathways. | Wu RC et al |
| 10823921 | 2000 | The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. | Xu J et al |
Other Information
Locus ID:
NCBI: 8202
MIM: 601937
HGNC: 7670
Ensembl: ENSG00000124151
Variants:
dbSNP: 8202
ClinVar: 8202
TCGA: ENSG00000124151
COSMIC: NCOA3
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000124151 | ENST00000371997 | Q9Y6Q9 |
| ENSG00000124151 | ENST00000371998 | Q9Y6Q9 |
| ENSG00000124151 | ENST00000372004 | Q9Y6Q9 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38483947 | 2024 | Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy. | 2 |
| 38483947 | 2024 | Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy. | 2 |
| 36658474 | 2023 | Protective role of circRNA CCND1 in ulcerative colitis via miR-142-5p/NCOA3 axis. | 3 |
| 36658474 | 2023 | Protective role of circRNA CCND1 in ulcerative colitis via miR-142-5p/NCOA3 axis. | 3 |
| 33509057 | 2022 | PAX2 promoter methylation and AIB1 overexpression promote tamoxifen resistance in breast carcinoma patients. | 4 |
| 34251576 | 2022 | NCOA3 is a critical oncogene in thyroid cancer via the modulation of major signaling pathways. | 6 |
| 35521817 | 2022 | ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma. | 0 |
| 33509057 | 2022 | PAX2 promoter methylation and AIB1 overexpression promote tamoxifen resistance in breast carcinoma patients. | 4 |
| 34251576 | 2022 | NCOA3 is a critical oncogene in thyroid cancer via the modulation of major signaling pathways. | 6 |
| 35521817 | 2022 | ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma. | 0 |
| 33326993 | 2021 | NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss. | 9 |
| 33408774 | 2021 | Upregulation of amplified in breast cancer 1 contributes to pancreatic ductal adenocarcinoma progression and vulnerability to blockage of hedgehog activation. | 3 |
| 33420368 | 2021 | Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype. | 7 |
| 33564037 | 2021 | Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs. | 14 |
| 33589584 | 2021 | Targeting NSD2-mediated SRC-3 liquid-liquid phase separation sensitizes bortezomib treatment in multiple myeloma. | 35 |
Citation
Sarah L Anzick
NCOA3 (Nuclear Receptor Coactivator 3)
Atlas Genet Cytogenet Oncol Haematol. 2005-04-01
Online version: http://atlasgeneticsoncology.org/gene/505/ncoa3
