Nuclear receptor coactivator 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).

NCOA2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GWQ, 1GWR, 1M2Z, 1MV9, 1MVC, 1MZN, 1P93, 1T63, 1T65, 1UHL, 1YOK, 1ZDT, 1ZDU, 1ZKY, 2AO6, 2B1V, 2B1Z, 2B23, 2FAI, 2G44, 2G5O, 2P15, 2P1T, 2P1U, 2P1V, 2Q7J, 2Q7L, 2ZXZ, 2ZY0, 3A9E, 3DZU, 3DZY, 3E00, 3E7C, 3E94, 3FUG, 3GN8, 3K23, 3KWY, 3KYT, 3L0E, 3L0L, 3O1D, 3O1E, 3OAP, 3OZJ, 3PCU, 3PLZ, 3Q95, 3Q97, 3R5M, 3UP0, 3UP3, 4DOS, 4E2J, 4FHH, 4FHI, 4IA1, 4IA2, 4IA3, 4IA7, 4IQR, 4IU7, 4IUI, 4IV2, 4IV4, 4IVW, 4IVY, 4IW6, 4IW8, 4IWC, 4IWF, 2LDC, 2YJD, 3CLD, 3ERD, 3K22, 4CSJ, 4K4J, 4K6I, 4M8E, 4M8H, 4NIE, 4NQA, 4OC7, 4P6W, 4P6X, 4POH, 4POJ, 4PP3, 4PP5, 4PP6, 4PPP, 4PPS, 4PXM, 4Q0A, 4WG0, 4QE6, 4QE8, 4RFW, 4RMC, 4RMD, 4RME, 4ZN9, 4ZO1, 4RUO, 5APJ, 4UDD, 4PLD, 4PLE, 4UDC, 5APH, 5DMC, 5DKB, 5DMF, 4ZNV, 5DVS, 5DL4, 5E0W, 5E19, 4ZUC, 5DI7, 5I4V, 5E0X, 5E1C, 4ZWK, 5DYD, 5DIG, 5DKG, 5DTV, 5EC9, 5DX3, 5DRM, 5BP6, 5DYB, 5DLR, 5E14, 5DXK, 5DUH, 5DVV, 5DU5, 5DXP, 5DP0, 4ZNS, 5DZ3, 5DXR, 5DXQ, 5DZI, 4ZNT, 4ZNW, 5DID, 5DXM, 5EHJ, 5BQ4, 5DY8, 4ZSH, 5DXB, 5DUG, 5DK9, 5EIT, 5BPR, 5DWJ, 5DWI, 5HYR, 5DKS, 4ZUB, 5EI1, 5DZ0, 4ZNU, 4ZNH, 5E15, 4ZN7, 5DZ1, 5DUE, 4ZWH, 5EGV, 5BNU, 5DIE, 5DKE, 5DWG, 5DZH, 5DRJ, 5DWE
Identifiers
Aliases	NCOA2, GRIP1, KAT13C, NCoA-2, SRC2, TIF2, bHLHe75, nuclear receptor coactivator 2
External IDs	OMIM: 601993 MGI: 1276533 HomoloGene: 4768 GeneCards: NCOA2
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q13.3 Start 70,109,782 bp[1] End 70,403,808 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 A3|1 4.12 cM Start 13,139,105 bp[2] End 13,374,083 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein dimerization activity • thyroid hormone receptor coactivator activity • GO:0001105 transcription coactivator activity • transcription factor binding • chromatin binding • nuclear hormone receptor binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001948 protein binding • ligand-dependent nuclear receptor transcription coactivator activity • RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding • receptor binding • ligand-dependent nuclear receptor binding • aryl hydrocarbon receptor binding • protein domain specific binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cytoplasm • nucleoplasm • cell nucleus • nuclear body • macromolecular complex Biological process • regulation of transcription, DNA-templated • cellular response to Thyroglobulin triiodothyronine • rhythmic process • negative regulation of transcription from RNA polymerase II promoter • circadian regulation of gene expression • transcription, DNA-templated • cellular response to hormone stimulus • regulation of glucose metabolic process • circadian rhythm • bile acid and bile salt transport • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • locomotor rhythm • intracellular receptor signaling pathway • regulation of lipid metabolic process • regulation of gene expression • response to progesterone Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10499	17978
Ensembl	ENSG00000140396	ENSMUSG00000005886
UniProt	Q15596	Q61026
RefSeq (mRNA)	NM_006540 NM_001321703 NM_001321707 NM_001321711 NM_001321712 NM_001321713	NM_001077695 NM_008678 NM_001302702
RefSeq (protein)	NP_001308632 NP_001308636 NP_001308640 NP_001308641 NP_001308642 NP_006531	NP_001289631 NP_032704
Location (UCSC)	Chr 8: 70.11 – 70.4 Mb	Chr 1: 13.14 – 13.37 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

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.[5][6]

GRIP1 is a transcriptional co-activator of the glucocorticoid receptor and interferon regulatory factor 1 (IRF1).[7]

Interactions

Nuclear receptor coactivator 2 has been shown to interact with:

• AR,[8][9][10][11][12]
• ARNT,[13]
• BRCA1,[14][15]
• DDX17,[16]
• DDX5,[16]
• ESR1,[11][16][17][18][19]
• NR3C1,[20][21]
• PPFIA4,[22]
• PPARG,[23]
• RXRA,[24][25]
• SRA1,[16] and
• VDR.[11][17][24][26]

References

1. GRCh38: Ensembl release 89: ENSG00000140396 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000005886 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. doi:10.1002/j.1460-2075.1996.tb00736.x. PMC 452006. PMID 8670870.
6. 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. doi:10.1128/MCB.17.5.2735. PMC 232124. PMID 9111344.
7. Bhandare R, Damera G, Banerjee A, Flammer JR, Keslacy S, Rogatsky I, Panettieri RA, Amrani Y, Tliba O (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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K, Nelson WE, Probst MR, Rosenfeld MG, Hankinson O (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.
14. 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.
15. Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA (2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID 11085509.
16. Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (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.
17. Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (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.
18. 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.
19. 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.
20. 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.
21. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE (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.
22. Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pagès C, Streuli M, Weinberg RJ, Sheng M (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.
23. 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.
24. 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.
25. 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.
26. 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.

Further reading

• 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. doi:10.1002/j.1460-2075.1996.tb00736.x. PMC 452006. 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. doi:10.1128/MCB.17.5.2735. PMC 232124. PMID 9111344.
• Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H (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. PMC 1170401. 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. doi:10.1182/blood.V91.9.3127. 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, Trapman J, Brinkmann AO (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. PMC 3968904. PMID 9812974.
• Hong H, Darimont BD, Ma H, Yang L, Yamamoto KR, Stallcup MR (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, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR (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, Irvine RA, Webb P, Kushner PJ, Coetzee GA, Stallcup MR (1999). "Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins". Mol. Cell. Biol. 19 (9): 6164–73. doi:10.1128/MCB.19.9.6164. PMC 84548. PMID 10454563.
• Atkins GB, Hu X, Guenther MG, Rachez C, Freedman LP, Lazar MA (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, O'Brien S, Tanaka H, Poellinger L (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. doi:10.1128/MCB.20.1.402-415.2000. PMC 85095. PMID 10594042.
• 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.
• 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, Shaul PW, Brown M, Mendelsohn ME (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. PMC 16016. 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, 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.
• 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, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA (2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID 11085509.

External links

• nuclear receptor coactivator 2 at the US National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C90
• Overview of all the structural information available in the PDB for UniProt: Q15596 (Human Nuclear receptor coactivator 2) at the PDBe-KB.
• Overview of all the structural information available in the PDB for UniProt: Q61026 (Mouse Nuclear receptor coactivator 2) at the PDBe-KB.