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

Identity

HGNC
LOCATION
20q13.12
IMAGE
Atlas 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

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.

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

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.

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

Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 8202
MIM: 601937
HGNC: 7670
Ensembl: ENSG00000124151

Variants:

dbSNP: 8202
ClinVar: 8202
TCGA: ENSG00000124151
COSMIC: NCOA3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000124151ENST00000371997Q9Y6Q9
ENSG00000124151ENST00000371998Q9Y6Q9
ENSG00000124151ENST00000372004Q9Y6Q9

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
Thyroid hormone signaling pathwayKEGGhsa04919
Signal TransductionREACTOMER-HSA-162582
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK6/MAPK4 signalingREACTOMER-HSA-5687128
MetabolismREACTOMER-HSA-1430728
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
Low
Medium
High

References

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

Citation

Sarah L Anzick

NCOA3 (Nuclear Receptor Coactivator 3)

Atlas Genet Cytogenet Oncol Haematol. 2005-04-01

Online version: http://atlasgeneticsoncology.org/gene/505/welcome