Nuclear receptor coactivator 2

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Nuclear receptor coactivator 2
PDB 1gwq EBI.jpg
Rendering of 1GWQ
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NCOA2 ; GRIP1; KAT13C; NCoA-2; SRC2; TIF2; bHLHe75
External IDs OMIM601993 MGI1276533 HomoloGene4768 IUPHAR: 2694 ChEMBL: 1615341 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:
71.02 – 71.32 Mb
Chr 1:
13.14 – 13.37 Mb
PubMed search [1] [2]

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).


NCoA-2 is a transcriptional coregulatory protein that 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 acetylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA2 assists nuclear receptors in the upregulation of DNA expression.[1][2]

GRIP1 is a transcriptional co-activator of the glucocorticoid receptor and interferon regulatory factor 1 (IRF1).[3]


Nuclear receptor coactivator 2 has been shown to interact with:


  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. PMC 452006. 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. PMC 232124. PMID 9111344. 
  3. ^ Bhandare R, Damera G, Banerjee A, Flammer JR, Keslacy S, Rogatsky I et al. (January 2010). "Glucocorticoid receptor interacting protein-1 restores glucocorticoid responsiveness in steroid-resistant airway structural cells". Am. J. Respir. Cell Mol. Biol. 42 (1): 9–15. doi:10.1165/rcmb.2009-0239RC. PMC 2809222. PMID 19805480. 
  4. ^ Song LN, Coghlan M, Gelmann EP (2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. 18 (1): 70–85. doi:10.1210/me.2003-0189. PMID 14593076. 
  5. ^ Ishitani K, Yoshida T, Kitagawa H, Ohta H, Nozawa S, Kato S (2003). "p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor". Biochem. Biophys. Res. Commun. 306 (3): 660–5. doi:10.1016/S0006-291X(03)01021-0. PMID 12810069. 
  6. ^ Wang Q, Udayakumar TS, Vasaitis TS, Brodie AM, Fondell JD (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. 
  7. ^ a b c He B, Wilson EM (2003). "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs". Mol. Cell. Biol. 23 (6): 2135–50. doi:10.1128/MCB.23.6.2135-2150.2003. PMC 149467. PMID 12612084. 
  8. ^ Bai S, He B, Wilson EM (2005). "Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction". Mol. Cell. Biol. 25 (4): 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. PMC 548016. PMID 15684378. 
  9. ^ Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K et al. (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. 22 (12): 4319–33. doi:10.1128/MCB.22.12.4319-4333.2002. PMC 133867. PMID 12024042. 
  10. ^ Rodriguez M, Yu X, Chen J, Songyang Z (2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi:10.1074/jbc.C300407200. PMID 14578343. 
  11. ^ Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD et al. (2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID 11085509. 
  12. ^ a b c d Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y et al. (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. ^ a b Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D et al. (2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell 113 (7): 905–17. doi:10.1016/S0092-8674(03)00436-7. PMID 12837248. 
  14. ^ Wärnmark A, Treuter E, Gustafsson JA, Hubbard RE, Brzozowski AM, Pike AC (2002). "Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha". J. Biol. Chem. 277 (24): 21862–8. doi:10.1074/jbc.M200764200. PMID 11937504. 
  15. ^ Fenne IS, Hoang T, Hauglid M, Sagen JV, Lien EA, Mellgren G (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 149 (9): 4336–45. doi:10.1210/en.2008-0037. PMID 18499756. 
  16. ^ Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (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. 
  17. ^ Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD et al. (2002). "Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition". Cell 110 (1): 93–105. doi:10.1016/S0092-8674(02)00817-6. PMID 12151000. 
  18. ^ Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pagès C et al. (2002). "Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting". Neuron 34 (1): 39–52. doi:10.1016/S0896-6273(02)00640-2. PMID 11931740. 
  19. ^ Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (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. 
  20. ^ a b Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN (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. 276 (44): 40614–20. doi:10.1074/jbc.M106263200. PMID 11514567. 
  21. ^ Lee WY, Noy N (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. 
  22. ^ 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. 

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