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Nuclear receptor coactivator 2: Wikis


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Nuclear receptor coactivator 2
Symbols NCOA2; GRIP1; MGC138808; NCoA-2; TIF2
External IDs OMIM601993 MGI1276533 HomoloGene4768 GeneCards: NCOA2 Gene
RNA expression pattern
PBB GE NCOA2 gnf1h04995 s at tn.png
More reference expression data
Species Human Mouse
Entrez 10499 17978
Ensembl ENSG00000140396 ENSMUSG00000005886
UniProt Q15596 Q61026
RefSeq (mRNA) NM_006540 NM_001077695
RefSeq (protein) NP_006531 NP_001071163
Location (UCSC) Chr 8:
71.2 - 71.48 Mb
Chr 1:
13.13 - 13.36 Mb
PubMed search [1] [2]

The nuclear receptor coactivator 2 (NCOA2) is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA2 is recruited to DNA promotion sites by ligand activated nuclear receptors. NCOA2 in turn acylates histones which makes downsteam DNA more accessible to transcription. Hence NCOA2 assists nuclear receptors in the upregulation of DNA expression.[1][2]

NCOA2 is also frequently called glucocorticoid receptor interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).



Nuclear receptor coactivator 2 has been shown to interact with DDX17,[3] Androgen receptor,[4][5][6][7][8] Glucocorticoid receptor,[9][10] BRCA1,[11][12] Peroxisome proliferator-activated receptor gamma,[13] Aryl hydrocarbon receptor nuclear translocator,[14] Estrogen receptor alpha,[15][16][3][7][17] PPFIA4,[18] DDX5,[3] Calcitriol receptor,[15][19][20][7] SRA1[3] and Retinoid X receptor alpha.[21][20]


  1. ^ Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H (1996). "TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors". EMBO J 15 (14): 3667–75. PMID 8670870.  
  2. ^ Hong H, Kohli K, Garabedian MJ, Stallcup MR (1997). "GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors". Mol Cell Biol 17 (5): 2735–44. PMID 9111344.  
  3. ^ a b c d 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. PMID 11250900.  
  4. ^ Song, Liang-Nian; Coghlan Meghan, Gelmann Edward P (Jan. 2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. (United States) 18 (1): 70–85. doi:10.1210/me.2003-0189. ISSN 0888-8809. PMID 14593076.  
  5. ^ Ishitani, Ken; Yoshida Tasuku, Kitagawa Hirochika, Ohta Hiroaki, Nozawa Shiro, Kato Shigeaki (Jul. 2003). "p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor". Biochem. Biophys. Res. Commun. (United States) 306 (3): 660–5. ISSN 0006-291X. PMID 12810069.  
  6. ^ 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.  
  7. ^ a b c He, Bin; Wilson Elizabeth M (Mar. 2003). "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs". Mol. Cell. Biol. (United States) 23 (6): 2135–50. ISSN 0270-7306. PMID 12612084.  
  8. ^ Bai, Suxia; He Bin, Wilson Elizabeth M (Feb. 2005). "Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction". Mol. Cell. Biol. (United States) 25 (4): 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. ISSN 0270-7306. PMID 15684378.  
  9. ^ 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. ISSN 0888-8809. PMID 11266503.  
  10. ^ Bledsoe, Randy K; Montana Valerie G, Stanley Thomas B, Delves Chris J, Apolito Christopher J, McKee David D, Consler Thomas G, Parks Derek J, Stewart Eugene L, Willson Timothy M, Lambert Millard H, Moore John T, Pearce Kenneth H, Xu H Eric (Jul. 2002). "Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition". Cell (United States) 110 (1): 93–105. ISSN 0092-8674. PMID 12151000.  
  11. ^ Rodriguez, Maria; Yu Xiaochun, Chen Junjie, Songyang Zhou (Dec. 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. (United States) 278 (52): 52914–8. doi:10.1074/jbc.C300407200. ISSN 0021-9258. PMID 14578343.  
  12. ^ Park, J J; Irvine R A, Buchanan G, Koh S S, Park J M, Tilley W D, Stallcup M R, Press M F, Coetzee G A (Nov. 2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. (UNITED STATES) 60 (21): 5946–9. ISSN 0008-5472. PMID 11085509.  
  13. ^ 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.  
  14. ^ Beischlag, Timothy V; Wang Song, Rose David W, Torchia Joseph, Reisz-Porszasz Suzanne, Muhammad Khurshid, Nelson Walter E, Probst Markus R, Rosenfeld Michael G, Hankinson Oliver (Jun. 2002). "Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex". Mol. Cell. Biol. (United States) 22 (12): 4319–33. ISSN 0270-7306. PMID 12024042.  
  15. ^ a b Kitagawa, Hirochika; Fujiki Ryoji, Yoshimura Kimihiro, Mezaki Yoshihiro, Uematsu Yoshikatsu, Matsui Daisuke, Ogawa Satoko, Unno Kiyoe, Okubo Mataichi, Tokita Akifumi, Nakagawa Takeya, Ito Takashi, Ishimi Yukio, Nagasawa Hiromichi, Matsumoto Toshio, Yanagisawa Junn, Kato Shigeaki (Jun. 2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell (United States) 113 (7): 905–17. ISSN 0092-8674. PMID 12837248.  
  16. ^ Wärnmark, Anette; Treuter Eckardt, Gustafsson Jan-Ake, Hubbard Roderick E, Brzozowski Andrzej M, Pike Ashley C W (Jun. 2002). "Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha". J. Biol. Chem. (United States) 277 (24): 21862–8. doi:10.1074/jbc.M200764200. ISSN 0021-9258. PMID 11937504.  
  17. ^ Fenne, Ingvild S; Hoang Tuyen, Hauglid Marianne, Sagen Jørn Vegard, Lien Ernst A, Mellgren Gunnar (Sep. 2008). "Recruitment of coactivator glucocorticoid receptor interacting protein 1 to an estrogen receptor transcription complex is regulated by the 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase". Endocrinology (United States) 149 (9): 4336–45. doi:10.1210/en.2008-0037. ISSN 0013-7227. PMID 18499756.  
  18. ^ Wyszynski, Michael; Kim Eunjoon, Dunah Anthone W, Passafaro Maria, Valtschanoff Juli G, Serra-Pagès Carles, Streuli Michel, Weinberg Richard J, Sheng Morgan (Mar. 2002). "Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting". Neuron (United States) 34 (1): 39–52. ISSN 0896-6273. PMID 11931733.  
  19. ^ Herdick, M; Steinmeyer A, Carlberg C (Jun. 2000). "Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators". J. Biol. Chem. (UNITED STATES) 275 (22): 16506–12. doi:10.1074/jbc.M910000199. ISSN 0021-9258. PMID 10748178.  
  20. ^ a b Zhang, C; Baudino T A, Dowd D R, Tokumaru H, Wang W, MacDonald P N (Nov. 2001). "Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription". J. Biol. Chem. (United States) 276 (44): 40614–20. doi:10.1074/jbc.M106263200. ISSN 0021-9258. PMID 11514567.  
  21. ^ 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. ISSN 0006-2960. PMID 11851396.  

External links

Further reading

  • Voegel JJ, Heine MJ, Zechel C, et al. (1996). "TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors.". Embo J. 15 (14): 3667–75. PMID 8670870.  
  • Hong H, Kohli K, Garabedian MJ, Stallcup MR (1997). "GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors.". Mol. Cell. Biol. 17 (5): 2735–44. PMID 9111344.  
  • Voegel JJ, Heine MJ, Tini M, et al. (1998). "The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways.". Embo J. 17 (2): 507–19. doi:10.1093/emboj/17.2.507. PMID 9430642.  
  • Carapeti M, Aguiar RC, Goldman JM, Cross NC (1998). "A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia.". Blood 91 (9): 3127–33. PMID 9558366.  
  • Fryer CJ, Archer TK (1998). "Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex.". Nature 393 (6680): 88–91. doi:10.1038/30032. PMID 9590696.  
  • Berrevoets CA, Doesburg P, Steketee K, et al. (1998). "Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2).". Mol. Endocrinol. 12 (8): 1172–83. doi:10.1210/me.12.8.1172. PMID 9717843.  
  • 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.  
  • Hong H, Darimont BD, Ma H, et al. (1999). "An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors.". J. Biol. Chem. 274 (6): 3496–502. doi:10.1074/jbc.274.6.3496. PMID 9920895.  
  • Chen D, Ma H, Hong H, et al. (1999). "Regulation of transcription by a protein methyltransferase.". Science 284 (5423): 2174–7. doi:10.1126/science.284.5423.2174. PMID 10381882.  
  • Ma H, Hong H, Huang SM, et al. (1999). "Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins.". Mol. Cell. Biol. 19 (9): 6164–73. PMID 10454563.  
  • Atkins GB, Hu X, Guenther MG, et al. (1999). "Coactivators for the orphan nuclear receptor RORalpha.". Mol. Endocrinol. 13 (9): 1550–7. doi:10.1210/me.13.9.1550. PMID 10478845.  
  • Carrero P, Okamoto K, Coumailleau P, et al. (2000). "Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha.". Mol. Cell. Biol. 20 (1): 402–15. PMID 10594042.  
  • 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.  
  • Naltner A, Ghaffari M, Whitsett JA, Yan C (2000). "Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent.". J. Biol. Chem. 275 (1): 56–62. doi:10.1074/jbc.275.1.56. PMID 10617585.  
  • Jimenez-Lara AM, Heine MJ, Gronemeyer H (2000). "Cloning of a mouse glucocorticoid modulatory element binding protein, a new member of the KDWK family.". FEBS Lett. 468 (2-3): 203–10. doi:10.1016/S0014-5793(00)01209-6. PMID 10692587.  
  • Poelzl G, Kasai Y, Mochizuki N, et al. (2000). "Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2.". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2836–9. doi:10.1073/pnas.050580997. PMID 10706629.  
  • Herdick M, Steinmeyer A, Carlberg C (2000). "Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators.". J. Biol. Chem. 275 (22): 16506–12. doi:10.1074/jbc.M910000199. PMID 10748178.  
  • Kodera Y, Takeyama K, Murayama A, et al. (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.  
  • Koh SS, Chen D, Lee YH, Stallcup MR (2001). "Synergistic enhancement of nuclear receptor function by p160 coactivators and two coactivators with protein methyltransferase activities.". J. Biol. Chem. 276 (2): 1089–98. doi:10.1074/jbc.M004228200. PMID 11050077.  
  • Park JJ, Irvine RA, Buchanan G, et al. (2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor.". Cancer Res. 60 (21): 5946–9. PMID 11085509.  


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