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NCOA3 (Nuclear Receptor Coactivator 3)

Written2005-04Sarah 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

(Note : for Links provided by Atlas : click)

Identity

Other aliasAIB1 (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)
LocusID (NCBI) 8202
Atlas_Id 505
Location 20q13.12  [Link to chromosome band 20q13]
Location_base_pair Starts at and ends at bp from pter
 
  AIB1 (20q12)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ANTXR1 (2p13.3) / NCOA3 (20q13.12)C4orf48 (4p16.3) / NCOA3 (20q13.12)KAT6A (8p11.21) / NCOA3 (20q13.12)
NCOA3 (20q13.12) / CD36 (7q21.11)NCOA3 (20q13.12) / DUSP15 (20q11.21)NCOA3 (20q13.12) / EYA2 (20q13.12)
NCOA3 (20q13.12) / SGK2 (20q13.12)NCOA3 (20q13.12) / SLAIN1 (13q22.3)NCOA3 (20q13.12) / SPINT1 (15q15.1)
NCOA3 (20q13.12) / TXNDC5 (6p24.3)NCOA3 (20q13.12) / ZMYND8 (20q13.12)PTPRT (20q12) / NCOA3 (20q13.12)
SPINK1 (5q32) / NCOA3 (20q13.12)STAT5B (17q21.2) / NCOA3 (20q13.12)XPO6 (16p11.2) / NCOA3 (20q13.12)

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.

Bibliography

AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.
Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS
Science (New York, N.Y.). 1997 ; 277 (5328) : 965-968.
PMID 9252329
 
In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity.
Bautista S, Vallès H, Walker RL, Anzick S, Zeillinger R, Meltzer P, Theillet C
Clinical cancer research : an official journal of the American Association for Cancer Research. 1998 ; 4 (12) : 2925-2929.
PMID 9865902
 
Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.
Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM
Cell. 1997 ; 90 (3) : 569-580.
PMID 9267036
 
Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas.
Ghadimi BM, Schröck E, Walker RL, Wangsa D, Jauho A, Meltzer PS, Ried T
The American journal of pathology. 1999 ; 154 (2) : 525-536.
PMID 10027410
 
Gene amplification and expression of the steroid receptor coactivator SRC3 (AIB1) in sporadic breast and endometrial carcinomas.
Glaeser M, Floetotto T, Hanstein B, Beckmann MW, Niederacher D
Hormone and metabolic research. Hormon- und Stoffwechselforschung. Hormones et metabolisme. 2001 ; 33 (3) : 121-126.
PMID 11355743
 
Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu.
Goel A, Janknecht R
The Journal of biological chemistry. 2004 ; 279 (15) : 14909-14916.
PMID 14747462
 
Polymorphic repeat in AIB1 does not alter breast cancer risk.
Haiman CA, Hankinson SE, Spiegelman D, Colditz GA, Willett WC, Speizer FE, Brown M, Hunter DJ
Breast cancer research : BCR. 2000 ; 2 (5) : 378-385.
PMID 11056690
 
Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during progression of pancreatic adenocarcinoma.
Henke RT, Haddad BR, Kim SE, Rone JD, Mani A, Jessup JM, Wellstein A, Maitra A, Riegel AT
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (18 Pt 1) : 6134-6142.
PMID 15448000
 
Polyglutamine repeat length in the AIB1 gene modifies breast cancer susceptibility in BRCA1 carriers.
Kadouri L, Kote-Jarai Z, Easton DF, Hubert A, Hamoudi R, Glaser B, Abeliovich D, Peretz T, Eeles RA
International journal of cancer. Journal international du cancer. 2004 ; 108 (3) : 399-403.
PMID 14648706
 
Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53.
Lee SK, Kim HJ, Kim JW, Lee JW
Molecular endocrinology (Baltimore, Md.). 1999 ; 13 (11) : 1924-1933.
PMID 10551785
 
The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation.
Li H, Chen JD
The Journal of biological chemistry. 1998 ; 273 (10) : 5948-5954.
PMID 9488734
 
RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.
Li H, Gomes PJ, Chen JD
Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (16) : 8479-8484.
PMID 9238002
 
Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer.
Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA, Wong J, Allred DC, Clark GM, Schiff R
Journal of the National Cancer Institute. 2003 ; 95 (5) : 353-361.
PMID 12618500
 
Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history.
Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen SL, Godwin AK, Daly MB, Narod SA, Brunet JS, Vesprini D, Garber JE, Lynch HT, Weber BL, Brown M
Cancer research. 2001 ; 61 (14) : 5420-5424.
PMID 11454686
 
An isoform of the coactivator AIB1 that increases hormone and growth factor sensitivity is overexpressed in breast cancer.
Reiter R, Wellstein A, Riegel AT
The Journal of biological chemistry. 2001 ; 276 (43) : 39736-39741.
PMID 11502741
 
Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers.
Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nakanishi M, Masuda K, Kimura A, Nakamura Y, Inazawa J, Abe T, Yamagishi H
International journal of cancer. Journal international du cancer. 2000 ; 89 (3) : 217-223.
PMID 10861496
 
A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity.
Suen CS, Berrodin TJ, Mastroeni R, Cheskis BJ, Lyttle CR, Frail DE
The Journal of biological chemistry. 1998 ; 273 (42) : 27645-27653.
PMID 9765300
 
TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1.
Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW
The Journal of biological chemistry. 1997 ; 272 (44) : 27629-27634.
PMID 9346901
 
The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function.
Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG
Nature. 1997 ; 387 (6634) : 677-684.
PMID 9192892
 
Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray.
Wang Y, Wu MC, Sham JS, Zhang W, Wu WQ, Guan XY
Cancer. 2002 ; 95 (11) : 2346-2352.
PMID 12436441
 
Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers.
Watanabe T, Imoto I, Katahira T, Hirasawa A, Ishiwata I, Emi M, Takayama M, Sato A, Inazawa J
Japanese journal of cancer research : Gann. 2002 ; 93 (10) : 1114-1122.
PMID 12417041
 
RAC-3 is a NF-kappa B coactivator.
Werbajh S, Nojek I, Lanz R, Costas MA
FEBS letters. 2000 ; 485 (2-3) : 195-199.
PMID 11094166
 
Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling pathways.
Wu RC, Qin J, Yi P, Wong J, Tsai SY, Tsai MJ, O'Malley BW
Molecular cell. 2004 ; 15 (6) : 937-949.
PMID 15383283
 
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, Liao L, Ning G, Yoshida-Komiya H, Deng C, O'Malley BW
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (12) : 6379-6384.
PMID 10823921
 

Citation

This paper should be referenced as such :
Anzick, SL
NCOA3 (nuclear receptor coactivator 3)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):216-218.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NCOA3ID505ch20q13.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  t(8;20)(p11;q13) KAT6A/NCOA3
t(8;16)(p11;p13) KAT6A/CREBBP
t(10;16)(q22;p13) KAT6B/CREBBP
t(8;20)(p11;q13) KAT6A/NCOA3


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]
  Ovarian tumours : an overview
dup(20)(q13q13) NCOA3/EYA2
t(15;20)(q15;q13) NCOA3/SPINT1
t(20;20)(q11;q13) NCOA3/DUSP15
NCOA3/EYA2 (20q13)
NCOA3/SGK2 (20q13)
PTPRT/NCOA3 (20q13)


External links

Nomenclature
Cards
AtlasNCOA3ID505ch20q13.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)8202
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:44:57 CEST 2018

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