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NCOA3 (Nuclear Receptor Coactivator 3)

Identity

Other namesAIB1 (amplified in breast cancer-1)
ACTR
RAC3 (RAR-associated coactivator 3)
SRC3 (steroid receptor coactivator protein 3)
TRAM-1 (thyroid hormone receptor activator molecule 1)
pCIP (p300/CBP-integrator associated protein; mouse)
HGNC (Hugo) NCOA3
Location 20q13.1
Location_base_pair Starts at 45564064 and ends at 45719021 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 
  AIB1 (20q12)

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)

Protein

 
  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.

To be noted

Overexpression of AIB1 in tamoxifen-treated patients is associated with tamoxifen resistance and worse survival. Tamoxifen behaves as estrogen in breast cancer cells that express high levels of AIB1 and HER2, resulting in de novo resistance.

An N-terminally deleted isoform (AIB1-Delta3) which lacks exon 3 was identified and found to be overexpressed in breast cancer cell lines and in tumors from breast cancer patients. Of interest, this splice variant has more potent transcriptional coactivation properties on estrogen and progesterone receptors than the full-length AIB1 protein.

External links

Nomenclature
HGNC (Hugo)NCOA3   7670
Entrez_Gene (NCBI)NCOA3  8202  nuclear receptor coactivator 3
Cards
AtlasNCOA3ID505ch20q13
GeneCards (Weizmann)NCOA3
Ensembl (Hinxton)ENSG00000124151 [Gene_View]  NCOA3 [Vega]
AceView (NCBI)NCOA3
Genatlas (Paris)NCOA3
euGene (Indiana)8202
SOURCE (Stanford)NM_006534 NM_181659
Genomic and cartography
GoldenPath (UCSC)NCOA3  -  20q13.1   chr20:45564064-45719021 +  20q12   [Description]    (hg18-Mar_2006)
EnsemblNCOA3 - 20q12 [CytoView]
Mapping of homologs : NCBINCOA3 [Mapview]
OMIM601937   
Gene and transcription
Gene : Genbank (Entrez)AB209863 AF010227 AF012108 AF016031 AF036892
Reference sequence (RefSeq transcript) :SRSNM_006534 NM_181659
Reference transcript : EntrezNM_006534 NM_181659
RefSeq genomic : SRSAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
RefSeq genomic : EntrezAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
Consensus coding sequences : CCDS NCBINCOA3
Cluster EST : UnigeneHs.592142 [ SRS ] Hs.592142 [ NCBI ]
Alternative Splicing : Fast-db (Paris)12948
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ9Y6Q9 (SRS) Q9Y6Q9 (Expasy) Q9Y6Q9 (Uniprot)
With graphics : InterProQ9Y6Q9
Splice isoforms : VarSplice FASTAQ9Y6Q9(VarSplice FASTA)
Domaine pattern : Prosite (SRS)HLH (PS50888)    PAS (PS50112)   
Domain pattern : Prosite (Expaxy)HLH (PS50888)    PAS (PS50112)   
Domains : Interpro (SRS)DUF1518    HLH_basic    Nuc_rcpt_coact_Ncoa-typ    Nuclear_rcpt_coactivator    PAS    PAS_fold    SRC-1   
Domains : Interpro (EBI)DUF1518    HLH_basic    Nuc_rcpt_coact_Ncoa-typ    Nuclear_rcpt_coactivator    PAS    PAS_fold    SRC-1   
Related proteins : CluSTrQ9Y6Q9
Domain families : Pfam SRSDUF1518 (PF07469)    HLH (PF00010)    Nuc_rec_co-act (PF08815)    PAS (PF00989)    SRC-1 (PF08832)   
Domain families : Pfam SangerDUF1518 (PF07469)    HLH (PF00010)    Nuc_rec_co-act (PF08815)    PAS (PF00989)    SRC-1 (PF08832)   
Domain families : Pfam NCBIpfam07469    pfam00010    pfam08815    pfam00989    pfam08832   
Domain families : Smart EMBLHLH (SM00353)PAS (SM00091)
Blocks (Seattle)Q9Y6Q9
Crystal structure of protein : PDB SRS1KBH   
Crystal structure of protein : PDBSum1KBH   
Crystal structure of protein : IMB1KBH   
Crystal structure of protein : PDB RSDB1KBH   
HPRD03570
Protein Interaction databases
DIP (DOE-UCLA)Q9Y6Q9
IntAct (EBI)Q9Y6Q9
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBINCOA3
SNP : GeneSNP UtahNCOA3
SNP : HGBaseNCOA3
Genetic variants : HAPMAPNCOA3
Somatic Mutations in Cancer : COSMICNCOA3 
Translocation Breakpoints in Cancer : TICdbNCOA3 
Mutations and Diseases : HGMDNCOA3
Hereditary diseases : OMIM601937   
Hereditary diseases : GENETests601937   
Diseases : Genetic AssociationNCOA3
General knowledge
Homologs : HomoloGeneNCOA3
Homology/Alignments : Family Browser UCSCNCOA3
Phylogenetic Trees/Animal Genes : TreeFamNCOA3
Catalytic activity : Enzyme2.3.1.48 [ Enzyme-Expasy ]   2.3.1.48 [ Enzyme-SRS ]   2.3.1.48 [ IntEnz-EBI ]   2.3.1.48 [ BRENDA ]   2.3.1.48 [ KEGG ]   
Chemical/Protein Interactions : CTD8202
Keywords Ontology : AmiGOtranscription coactivator activity  histone acetyltransferase activity  signal transducer activity  nucleus  cytoplasm  signal transduction  acyltransferase activity  transferase activity  androgen receptor signaling pathway  transcription regulator activity  positive regulation of transcription, DNA-dependent  thyroid hormone receptor binding  protein N-terminus binding  androgen receptor binding  
Keywords Ontology : EGO-EBItranscription coactivator activity  histone acetyltransferase activity  signal transducer activity  nucleus  cytoplasm  signal transduction  acyltransferase activity  transferase activity  androgen receptor signaling pathway  transcription regulator activity  positive regulation of transcription, DNA-dependent  thyroid hormone receptor binding  protein N-terminus binding  androgen receptor binding  
Pathways : BIOCARTATranscription Regulation by Methyltransferase of CARM1 [Genes]    Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells [Genes]    Control of Gene Expression by Vitamin D Receptor [Genes]   
Pathways : KEGG
Other databases
Probes
Probes : ImagenesNCOA3 Related clones (RZPD - Berlin)
Literature
PubMed129 Pubmed reference(s) in Entrez
PubGeneNCOA3

Bibliography

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Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers.
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Contributor(s)

Written04-2005Sarah 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

Citation

This paper should be referenced as such :
Anzick SL . NCOA3 (Nuclear Receptor Coactivator 3). Atlas Genet Cytogenet Oncol Haematol. April 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/NCOA3ID505ch20q13.html

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indexed on : Sat Jun 27 16:38:03 CEST 2009
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