NCOA3 (Nuclear Receptor Coactivator 3)

2005-04-01   Sarah L Anzick 

Cancer 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


Atlas Image
AIB1 (20q12)


Atlas Image
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.


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 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.


Chromosome 8 (AF010227)


Atlas Image
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.


A member of the p160/steroid receptor coactivator family. 1424 amino acids. 155 kDa (130 kDa encoded by isoform b).


Protein expression found in testis, lung, liver, brain, mammary gland, and heart.


Mainly cytoplasmic and weakly nuclear. The protein translocates to the nucleus upon TNF activation and phosphorylation.


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.



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


Pubmed IDLast YearTitleAuthors
92523291997AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.Anzick SL et al
98659021998In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity.Bautista S et al
92670361997Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.Chen H et al
100274101999Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas.Ghadimi BM et al
113557432001Gene amplification and expression of the steroid receptor coactivator SRC3 (AIB1) in sporadic breast and endometrial carcinomas.Glaeser M et al
147474622004Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu.Goel A et al
110566902000Polymorphic repeat in AIB1 does not alter breast cancer risk.Haiman CA et al
154480002004Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during progression of pancreatic adenocarcinoma.Henke RT et al
146487062004Polyglutamine repeat length in the AIB1 gene modifies breast cancer susceptibility in BRCA1 carriers.Kadouri L et al
105517851999Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53.Lee SK et al
94887341998The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation.Li H et al
92380021997RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.Li H et al
126185002003Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer.Osborne CK et al
114546862001Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history.Rebbeck TR et al
115027412001An isoform of the coactivator AIB1 that increases hormone and growth factor sensitivity is overexpressed in breast cancer.Reiter R et al
108614962000Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers.Sakakura C et al
97653001998A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity.Suen CS et al
93469011997TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1.Takeshita A et al
91928921997The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function.Torchia J et al
124364412002Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray.Wang Y et al
124170412002Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers.Watanabe T et al
110941662000RAC-3 is a NF-kappa B coactivator.Werbajh S et al
153832832004Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling pathways.Wu RC et al
108239212000The 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


dbSNP: 8202
ClinVar: 8202
TCGA: ENSG00000124151


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Thyroid hormone signaling pathwayKEGGhsa04919
Signal TransductionREACTOMER-HSA-162582
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK6/MAPK4 signalingREACTOMER-HSA-5687128
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Fatty acid, triacylglycerol, and ketone body metabolismREACTOMER-HSA-535734
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)REACTOMER-HSA-400206
PPARA activates gene expressionREACTOMER-HSA-1989781
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of white adipocyte differentiationREACTOMER-HSA-381340
Activation of HOX genes during differentiationREACTOMER-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesisREACTOMER-HSA-5617472
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
169401812006Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA.197
175740252007SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock.116
151698822004ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance.113
119719852002Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase.96
186448622008The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression.88
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
169239662006Signaling within a coactivator complex: methylation of SRC-3/AIB1 is a molecular switch for complex disassembly.82
192550642009Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk.70
201595522010SRC-3Delta4 mediates the interaction of EGFR with FAK to promote cell migration.64
215772002011Tumor-suppressor role for the SPOP ubiquitin ligase in signal-dependent proteolysis of the oncogenic co-activator SRC-3/AIB1.62


Sarah L Anzick

NCOA3 (Nuclear Receptor Coactivator 3)

Atlas Genet Cytogenet Oncol Haematol. 2005-04-01

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