Nuclear receptor coactivator 3

Nuclear receptor coactivator 3
NCOA3 activation domain 1 (AD1) bound to a portion of CBP. PDB rendering based on 1kbh.
Available structures PDB 1KBH, 3L3X, 3L3Z
Identifiers
Symbols	NCOA3; ACTR; AIB-1; AIB1; CAGH16; CTG26; KAT13B; MGC141848; RAC3; SRC-3; SRC3; TNRC14; TNRC16; TRAM-1; bHLHe42; pCIP
External IDs	OMIM: 601937 MGI: 1276535 HomoloGene: 4764 GeneCards: NCOA3 Gene
EC number	2.3.1.48
Gene Ontology Molecular function • chromatin binding • transcription coactivator activity • transcription coactivator activity • histone acetyltransferase activity • signal transducer activity • protein binding • acyltransferase activity • transferase activity • ligand-dependent nuclear receptor binding • estrogen receptor binding • ligand-dependent nuclear receptor transcription coactivator activity • nuclear hormone receptor binding • thyroid hormone receptor binding • protein N-terminus binding • androgen receptor binding Cellular component • nucleus • nucleoplasm • cytoplasm • Golgi apparatus Biological process • histone acetylation • androgen receptor signaling pathway • positive regulation of estrogen receptor signaling pathway • multicellular organism growth • cellular lipid metabolic process • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • developmental growth • positive regulation of sequence-specific DNA binding transcription factor activity • vagina development • mammary gland branching involved in thelarche Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8202	17979
Ensembl	ENSG00000124151	ENSMUSG00000027678
UniProt	Q9Y6Q9	O09000
RefSeq (mRNA)	NM_001174087.1	NM_008679.3
RefSeq (protein)	NP_001167558.1	NP_032705.2
Location (UCSC)	Chr 20: 46.13 – 46.29 Mb	Chr 2: 165.82 – 165.9 Mb
PubMed search	[1]	[2]

The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene.^[1][2] NCOA3 is also frequently called 'amplified in breast 1' (AIB1), steroid receptor coactivator-3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1).

Function

NCOA3 is a transcriptional coactivator protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA3 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA3, in turn, acylates histones, which makes downsteam DNA more accessible to transcription. Hence, NCOA3 assists nuclear receptors in the upregulation of gene expression.^[3][4]

Clinical significance

The ratio of PAX2 to AIB-1 protein expression may be predictive of the effectiveness of tamoxifen in breast cancer treatment.^[5][6]

Interactions

Nuclear receptor coactivator 3 has been shown to interact with DDX17,^[7] IKK2,^[8] Androgen receptor,^[9][10][11] CREB-binding protein,^[8][12] Glucocorticoid receptor,^[13][14] Peroxisome proliferator-activated receptor gamma,^[15] IKBKG,^[8] Estrogen receptor alpha,^[7][16][17] Estrogen receptor beta,^[16][18] DDX5,^[7] CHUK^[8] and Retinoid X receptor alpha.^[19][20]

References

1. ^ Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS (August 1997). "AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer". Science 277 (5328): 965–8. doi:10.1126/science.277.5328.965. PMID 9252329. 
2. ^ Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW (October 1997). "TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1". J. Biol. Chem. 272 (44): 27629–34. doi:10.1074/jbc.272.44.27629. PMID 9346901. 
3. ^ Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS (1997). "AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer". Science 277 (5328): 965–8. doi:10.1126/science.277.5328.965. PMID 9252329. 
4. ^ Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW (1997). "TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1". J Biol Chem 272 (44): 27629–34. doi:10.1074/jbc.272.44.27629. PMID 9346901. 
5. ^ "Study sheds new light on tamoxifen resistance". Cordis News. Cordis. 2008-11-13. http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RCN=30093. Retrieved 2008-11-14. 
6. ^ Hurtado A, Holmes KA, Geistlinger TR, Hutcheson IR, Nicholson RI, Brown M, Jiang J, Howat WJ, Ali S, Carroll JS (December 2008). "Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen". Nature 456 (7222): 663–6. doi:10.1038/nature07483. PMC 2920208. PMID 19005469. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2920208. 
7. ^ ^{a b c} Watanabe, M; Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (Mar. 2001). "A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA". EMBO J. (England) 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. ISSN 0261-4189. PMC 145523. PMID 11250900. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=145523. 
8. ^ ^{a b c d} Wu, Ray-Chang; Qin Jun, Hashimoto Yoshihiro, Wong Jiemin, Xu Jianming, Tsai Sophia Y, Tsai Ming-Jer, O'Malley Bert W (May. 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase". Mol. Cell. Biol. (United States) 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. ISSN 0270-7306. PMC 133790. PMID 11971985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133790. 
9. ^ Tan, J A; Hall S H, Petrusz P, French F S (Sep. 2000). "Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator". Endocrinology (UNITED STATES) 141 (9): 3440–50. doi:10.1210/en.141.9.3440. ISSN 0013-7227. PMID 10965917. 
10. ^ Gnanapragasam, V J; Leung H Y, Pulimood A S, Neal D E, Robson C N (Dec. 2001). "Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer". Br. J. Cancer (Scotland) 85 (12): 1928–36. doi:10.1054/bjoc.2001.2179. ISSN 0007-0920. PMC 2364015. PMID 11747336. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2364015. 
11. ^ Wang, Qianben; Udayakumar T S, Vasaitis Tadas S, Brodie Angela M, Fondell Joseph D (Apr. 2004). "Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells". J. Biol. Chem. (United States) 279 (17): 17319–28. doi:10.1074/jbc.M400970200. ISSN 0021-9258. PMID 14966121. 
12. ^ Naltner, A; Wert S, Whitsett J A, Yan C (Dec. 2000). "Temporal/spatial expression of nuclear receptor coactivators in the mouse lung". Am. J. Physiol. Lung Cell Mol. Physiol. (UNITED STATES) 279 (6): L1066–74. ISSN 1040-0605. PMID 11076796. 
13. ^ Hsiao, Pei-Wen; Fryer Christy J, Trotter Kevin W, Wang Weidong, Archer Trevor K (Sep. 2003). "BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation". Mol. Cell. Biol. (United States) 23 (17): 6210–20. doi:10.1128/MCB.23.17.6210-6220.2003. ISSN 0270-7306. PMC 180928. PMID 12917342. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=180928. 
14. ^ Zilliacus, J; Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson J A (Apr. 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. (United States) 15 (4): 501–11. doi:10.1210/me.15.4.501. ISSN 0888-8809. PMID 11266503. 
15. ^ Kodera, Y; Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (Oct. 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. (UNITED STATES) 275 (43): 33201–4. doi:10.1074/jbc.C000517200. ISSN 0021-9258. PMID 10944516. 
16. ^ ^{a b} Wong, C W; Komm B, Cheskis B J (Jun. 2001). "Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands". Biochemistry (United States) 40 (23): 6756–65. doi:10.1021/bi010379h. ISSN 0006-2960. PMID 11389589. 
17. ^ Tikkanen, M K; Carter D J, Harris A M, Le H M, Azorsa D O, Meltzer P S, Murdoch F E (Nov. 2000). "Endogenously expressed estrogen receptor and coactivator AIB1 interact in MCF-7 human breast cancer cells". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (23): 12536–40. doi:10.1073/pnas.220427297. ISSN 0027-8424. PMC 18799. PMID 11050174. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18799. 
18. ^ Leo, C; Li H, Chen J D (Feb. 2000). "Differential mechanisms of nuclear receptor regulation by receptor-associated coactivator 3". J. Biol. Chem. (UNITED STATES) 275 (8): 5976–82. doi:10.1074/jbc.275.8.5976. ISSN 0021-9258. PMID 10681591. 
19. ^ Chen, H; Lin R J, Schiltz R L, Chakravarti D, Nash A, Nagy L, Privalsky M L, Nakatani Y, Evans R M (Aug. 1997). "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300". Cell (UNITED STATES) 90 (3): 569–80. doi:10.1016/S0092-8674(00)80516-4. ISSN 0092-8674. PMID 9267036. 
20. ^ Lee, Wen-yi; Noy Noa (Feb. 2002). "Interactions of RXR with coactivators are differentially mediated by helix 11 of the receptor's ligand binding domain". Biochemistry (United States) 41 (8): 2500–8. doi:10.1021/bi011764. ISSN 0006-2960. PMID 11851396. 

External links

• MeSH nuclear receptor coactivator 3
• NURSA C91

Further reading

• Liao L, Kuang SQ, Yuan Y et al. (2003). "Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1". J. Steroid Biochem. Mol. Biol. 83 (1–5): 3–14. doi:10.1016/S0960-0760(02)00254-6. PMID 12650696. 
• Liu F, Ventura F, Doody J, Massagué J (1995). "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Mol. Cell. Biol. 15 (7): 3479–86. PMC 230584. PMID 7791754. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=230584. 
• Guan XY, Xu J, Anzick SL et al. (1996). "Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer". Cancer Res. 56 (15): 3446–50. PMID 8758910. 
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Margolis RL, Abraham MR, Gatchell SB et al. (1997). "cDNAs with long CAG trinucleotide repeats from human brain". Hum. Genet. 100 (1): 114–22. doi:10.1007/s004390050476. PMID 9225980. 
• Li H, Gomes PJ, Chen JD (1997). "RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2". Proc. Natl. Acad. Sci. U.S.A. 94 (16): 8479–84. doi:10.1073/pnas.94.16.8479. PMC 22964. PMID 9238002. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22964. 
• Anzick SL, Kononen J, Walker RL et al. (1997). "AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer". Science 277 (5328): 965–8. doi:10.1126/science.277.5328.965. PMID 9252329. 
• Chen H, Lin RJ, Schiltz RL et al. (1997). "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300". Cell 90 (3): 569–80. doi:10.1016/S0092-8674(00)80516-4. PMID 9267036. 
• Takeshita A, Cardona GR, Koibuchi N et al. (1997). "TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1". J. Biol. Chem. 272 (44): 27629–34. doi:10.1074/jbc.272.44.27629. PMID 9346901. 
• Korzus E, Torchia J, Rose DW et al. (1998). "Transcription factor-specific requirements for coactivators and their acetyltransferase functions". Science 279 (5351): 703–7. doi:10.1126/science.279.5351.703. PMID 9445475. 
• Shirazi SK, Bober MA, Coetzee GA (1998). "Polymorphic exonic CAG microsatellites in the gene amplified in breast cancer (AIB1 gene)". Clin. Genet. 54 (1): 102–3. doi:10.1111/j.1399-0004.1998.tb03704.x. PMID 9727751. 
• Wang JC, Stafford JM, Granner DK (1998). "SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4". J. Biol. Chem. 273 (47): 30847–50. doi:10.1074/jbc.273.47.30847. PMID 9812974. 
• Zwijsen RM, Buckle RS, Hijmans EM et al. (1999). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes Dev. 12 (22): 3488–98. doi:10.1101/gad.12.22.3488. PMC 317237. PMID 9832502. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317237. 
• Chen H, Lin RJ, Xie W et al. (1999). "Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase". Cell 98 (5): 675–86. doi:10.1016/S0092-8674(00)80054-9. PMID 10490106. 
• Ebisawa T, Tada K, Kitajima I et al. (2000). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell. Sci. 112 ( Pt 20): 3519–27. PMID 10504300. 
• Xie W, Hong H, Yang NN et al. (2000). "Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2". Mol. Endocrinol. 13 (12): 2151–62. doi:10.1210/me.13.12.2151. PMID 10598588. 
• Pao GM, Janknecht R, Ruffner H et al. (2000). "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5. doi:10.1073/pnas.97.3.1020. PMC 15508. PMID 10655477. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15508. 
• Leo C, Li H, Chen JD (2000). "Differential mechanisms of nuclear receptor regulation by receptor-associated coactivator 3". J. Biol. Chem. 275 (8): 5976–82. doi:10.1074/jbc.275.8.5976. PMID 10681591. 
• Font de Mora J, Brown M (2000). "AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor". Mol. Cell. Biol. 20 (14): 5041–7. doi:10.1128/MCB.20.14.5041-5047.2000. PMC 85954. PMID 10866661. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85954. 
• Tan JA, Hall SH, Petrusz P, French FS (2000). "Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator". Endocrinology 141 (9): 3440–50. doi:10.1210/en.141.9.3440. PMID 10965917.