NCOA3 (Nuclear Receptor Coactivator 3)

Identity

Other names	AIB1 (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	NCOA3
Location	20q13.1
Location_base_pair	Starts at 45564064 and ends at 45719021 bp from pter ( according to hg18-Mar_2006).
	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	NCOA3   7670
Entrez_Gene	NCOA3  8202  nuclear receptor coactivator 3
	Cards
Atlas	NCOA3ID505ch20q13
GeneCards	NCOA3
Ensembl	NCOA3 [Search_View]   ENSG00000124151 [Gene_View]  NCOA3 [Vega]
Genatlas	NCOA3
GeneLynx	NCOA3
eGenome	NCOA3
euGene	8202
	Genomic and cartography
GoldenPath	NCOA3  -  20q13.1   chr20:45564064-45719021 +  20q12   [Description]    (hg18-Mar_2006)
Ensembl	NCOA3 - 20q12 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	NCOA3
	Gene and transcription
Genbank	AB209863 [ ENTREZ ]
Genbank	AF010227 [ ENTREZ ]
Genbank	AF012108 [ ENTREZ ]
Genbank	AF016031 [ ENTREZ ]
Genbank	AF036892 [ ENTREZ ]
RefSeq	NM_006534 [ SRS ]    NM_006534 [ ENTREZ ]
RefSeq	NM_181659 [ SRS ]    NM_181659 [ ENTREZ ]
RefSeq	AC_000063 [ SRS ]    AC_000063 [ ENTREZ ]
RefSeq	AC_000152 [ SRS ]    AC_000152 [ ENTREZ ]
RefSeq	NC_000020 [ SRS ]    NC_000020 [ ENTREZ ]
RefSeq	NT_011362 [ SRS ]    NT_011362 [ ENTREZ ]
RefSeq	NW_001838666 [ SRS ]    NW_001838666 [ ENTREZ ]
RefSeq	NW_927339 [ SRS ]    NW_927339 [ ENTREZ ]
CCDS	NCOA3 CCDS - NCBI
AceView	NCOA3 AceView - NCBI
Unigene	Hs.697989 [ SRS ]    Hs.697989 [ NCBI ]     HS697989 [ spliceNest ]
Fast-db	12948 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q0IIN7 [ SRS]    Q0IIN7 [ EXPASY ]     Q0IIN7 [ INTERPRO ]     Q0IIN7 [ UNIPROT ] Q0IIN7 [ VarSplice ]
Prosite	PS50888 HLH [ SRS ]    PS50888 HLH [ Expasy ]
Prosite	PS50112 PAS [ SRS ]    PS50112 PAS [ Expasy ]
Interpro	IPR010011 DUF1518 [ SRS ]    IPR010011 DUF1518 [ EBI ]
Interpro	IPR001092 HLH_basic [ SRS ]    IPR001092 HLH_basic [ EBI ]
Interpro	IPR014920 Nuc_rcpt_coact_Ncoa-typ [ SRS ]    IPR014920 Nuc_rcpt_coact_Ncoa-typ [ EBI ]
Interpro	IPR017426 Nuclear_rcpt_coactivator [ SRS ]    IPR017426 Nuclear_rcpt_coactivator [ EBI ]
Interpro	IPR000014 PAS [ SRS ]    IPR000014 PAS [ EBI ]
Interpro	IPR013767 PAS_fold [ SRS ]    IPR013767 PAS_fold [ EBI ]
Interpro	IPR014935 SRC-1 [ SRS ]    IPR014935 SRC-1 [ EBI ]
CluSTr	Q0IIN7
Pfam	PF07469 DUF1518 [ SRS ]    PF07469 DUF1518 [ Sanger ]    pfam07469 [ NCBI-CDD ]
Pfam	PF00010 HLH [ SRS ]    PF00010 HLH [ Sanger ]    pfam00010 [ NCBI-CDD ]
Pfam	PF08815 Nuc_rec_co-act [ SRS ]    PF08815 Nuc_rec_co-act [ Sanger ]    pfam08815 [ NCBI-CDD ]
Pfam	PF00989 PAS [ SRS ]    PF00989 PAS [ Sanger ]    pfam00989 [ NCBI-CDD ]
Pfam	PF08832 SRC-1 [ SRS ]    PF08832 SRC-1 [ Sanger ]    pfam08832 [ NCBI-CDD ]
Smart	SM00353 HLH [EMBL]
Smart	SM00091 PAS [EMBL]
Blocks	Q0IIN7
HPRD	03570
	Protein Interaction databases
DIP	Q0IIN7
IntAct	Q0IIN7
	Polymorphism : SNP, mutations, diseases
OMIM	601937    [ map ]
GENECLINICS	601937
SNP	NCOA3 [dbSNP-NCBI]
SNP	NM_006534 [SNP-NCI]
SNP	NM_181659 [SNP-NCI]
SNP	NCOA3 [GeneSNPs - Utah]  NCOA3] [HGBASE - SRS]
HAPMAP	NCOA3 [HAPMAP]
COSMIC	NCOA3 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	NCOA3 [Translocation breakpoints In Cancer]
HGMD	NCOA3
Genetic Association	NCOA3
CDC HuGE	NCOA3
	General knowledge
Family Browser	NCOA3 [UCSC Family Browser]
SOURCE	NM_006534
SOURCE	NM_181659
SMD	Hs.697989
SAGE	Hs.697989
GO	transcription coactivator activity [Amigo]  transcription coactivator activity
GO	histone acetyltransferase activity [Amigo]  histone acetyltransferase activity
GO	signal transducer activity [Amigo]  signal transducer activity
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	signal transduction [Amigo]  signal transduction
GO	acyltransferase activity [Amigo]  acyltransferase activity
GO	transferase activity [Amigo]  transferase activity
GO	androgen receptor signaling pathway [Amigo]  androgen receptor signaling pathway
GO	transcription regulator activity [Amigo]  transcription regulator activity
GO	positive regulation of transcription, DNA-dependent [Amigo]  positive regulation of transcription, DNA-dependent
GO	thyroid hormone receptor binding [Amigo]  thyroid hormone receptor binding
GO	protein N-terminus binding [Amigo]  protein N-terminus binding
GO	androgen receptor binding [Amigo]  androgen receptor binding
BIOCARTA	Transcription Regulation by Methyltransferase of CARM1    [Genes]
BIOCARTA	Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells    [Genes]
BIOCARTA	Control of Gene Expression by Vitamin D Receptor    [Genes]
PubGene	NCOA3
TreeFam	NCOA3
CTD	8202 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	NCOA3 Related clones (RZPD - Berlin)
	PubMed
PubMed	108 Pubmed reference(s) in Entrez

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Polymorphic repeat in AIB1 does not alter breast cancer risk.

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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.

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Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history.

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PMID 11502741

Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray.

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PMID 12436441

Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers.

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Contributor(s)

Written	04-2005	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

Citation

This paper should be referenced as such :

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sun Nov 9 19:44:19 2008