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 Ortholog search: PDBe, RCSB List of PDB id codes 1KBH​, 3L3X​, 3L3Z​
Identifiers
Symbols	NCOA3 ; ACTR; AIB-1; AIB1; CAGH16; CTG26; KAT13B; RAC3; SRC-3; SRC3; TNRC14; TNRC16; TRAM-1; bHLHe42; pCIP
External IDs	OMIM: 601937 MGI: 1276535 HomoloGene: 4764 ChEMBL: 1615382 GeneCards: NCOA3 Gene
EC number	2.3.1.48
Gene ontology Molecular function • chromatin binding • transcription coactivator activity • histone acetyltransferase activity • protein binding • ligand-dependent nuclear receptor binding • ligand-dependent nuclear receptor transcription coactivator activity • nuclear hormone receptor binding • thyroid hormone receptor binding • protein dimerization activity • protein N-terminus binding • androgen receptor binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • cytoplasm • extracellular exosome Biological process • transcription, DNA-templated • positive regulation of gene expression • histone acetylation • androgen receptor signaling pathway • cellular response to hormone stimulus • multicellular organism growth • receptor transactivation • positive regulation of keratinocyte differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • vagina development • labyrinthine layer morphogenesis • mammary gland branching involved in thelarche • cellular response to estradiol stimulus • regulation of RNA biosynthetic process 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	NM_008679
RefSeq (protein)	NP_001167558	NP_032705
Location (UCSC)	Chr 20: 47.5 – 47.66 Mb	Chr 2: 165.99 – 166.07 Mb
PubMed search

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 downstream 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:

• Androgen receptor,^[7][8][9]
• CHUK^[10] and
• CREB-binding protein,^[10][11]
• DDX17,^[12]
• DDX5,^[12]
• Estrogen receptor alpha,^[12][13][14]
• Estrogen receptor beta,^[13][15]
• Glucocorticoid receptor,^[16][17]
• IKBKG,^[10]
• IKK2,^[10]
• Peroxisome proliferator-activated receptor gamma,^[18] 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. 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.
7. Tan JA, Hall SH, Petrusz P, French FS (September 2000). "Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator". Endocrinology 141 (9): 3440–50. doi:10.1210/endo.141.9.7680. PMID 10965917.
8. Gnanapragasam VJ, Leung HY, Pulimood AS, Neal DE, Robson CN (December 2001). "Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer". Br. J. Cancer 85 (12): 1928–36. doi:10.1054/bjoc.2001.2179. PMC 2364015. PMID 11747336.
9. Wang Q, Udayakumar TS, Vasaitis TS, Brodie AM, Fondell JD (April 2004). "Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells". J. Biol. Chem. 279 (17): 17319–28. doi:10.1074/jbc.M400970200. PMID 14966121.
10. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW (May 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase". Mol. Cell. Biol. 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. PMC 133790. PMID 11971985.
11. Naltner A, Wert S, Whitsett JA, Yan C (December 2000). "Temporal/spatial expression of nuclear receptor coactivators in the mouse lung". Am. J. Physiol. Lung Cell Mol. Physiol. 279 (6): L1066–74. PMID 11076796.
12. Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (March 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. 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. PMC 145523. PMID 11250900.
13. Wong CW, Komm B, Cheskis BJ (June 2001). "Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands". Biochemistry 40 (23): 6756–65. doi:10.1021/bi010379h. PMID 11389589.
14. Tikkanen MK, Carter DJ, Harris AM, Le HM, Azorsa DO, Meltzer PS, Murdoch FE (November 2000). "Endogenously expressed estrogen receptor and coactivator AIB1 interact in MCF-7 human breast cancer cells". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12536–40. doi:10.1073/pnas.220427297. PMC 18799. PMID 11050174.
15. Leo C, Li H, Chen JD (February 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.
16. Hsiao PW, Fryer CJ, Trotter KW, Wang W, Archer TK (September 2003). "BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation". Mol. Cell. Biol. 23 (17): 6210–20. doi:10.1128/MCB.23.17.6210-6220.2003. PMC 180928. PMID 12917342.
17. Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (April 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. 15 (4): 501–11. doi:10.1210/mend.15.4.0624. PMID 11266503.
18. Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (October 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. 275 (43): 33201–4. doi:10.1074/jbc.C000517200. PMID 10944516.
19. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (August 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.
20. Lee WY, Noy N (February 2002). "Interactions of RXR with coactivators are differentially mediated by helix 11 of the receptor's ligand binding domain". Biochemistry 41 (8): 2500–8. doi:10.1021/bi011764. PMID 11851396.

External links

• nuclear receptor coactivator 3 at the US National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C91

Further reading

• Liao L, Kuang SQ, Yuan Y, Gonzalez SM, O'Malley BW, Xu J (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. doi:10.1128/mcb.15.7.3479. PMC 230584. PMID 7791754.
• Guan XY, Xu J, Anzick SL, Zhang H, Trent JM, Meltzer PS (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, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (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.
• 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.
• Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (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, 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.
• Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG (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, Loomans CJ, Bernards R (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.
• Chen H, Lin RJ, Xie W, Wilpitz D, Evans RM (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, Tojo K, Sampath TK, Kawabata M, Miyazono K, Imamura T (2000). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell. Sci. 112 (20): 3519–27. PMID 10504300.
• Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM (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, Hunter T, Verma IM (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.
• 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.
• 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/endo.141.9.7680. PMID 10965917.