Nuclear receptor co-repressor 2

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Nuclear receptor corepressor 2
Protein NCOR2 PDB 1xc5.png
PDB rendering based on 1xc5.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NCOR2 ; CTG26; N-CoR2; SMAP270; SMRT; SMRTE; SMRTE-tau; TNRC14; TRAC; TRAC-1; TRAC1
External IDs OMIM600848 MGI1337080 HomoloGene31370 ChEMBL: 5949 GeneCards: NCOR2 Gene
RNA expression pattern
PBB GE NCOR2 207760 s at tn.png
PBB GE NCOR2 208888 s at tn.png
PBB GE NCOR2 208889 s at tn.png
More reference expression data
Species Human Mouse
Entrez 9612 20602
Ensembl ENSG00000196498 ENSMUSG00000029478
UniProt Q9Y618 Q9WU42
RefSeq (mRNA) NM_001077261 NM_001253904
RefSeq (protein) NP_001070729 NP_001240833
Location (UCSC) Chr 12:
124.32 – 124.57 Mb
Chr 5:
125.02 – 125.18 Mb
PubMed search [1] [2]

The nuclear receptor co-repressor 2 (NCOR2) is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression.[1][2] NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT)[1] or T3 receptor-associating cofactor 1 (TRAC-1).[2]


NCOR2/SMRT is a transcriptional coregulatory protein that contains several modulatory functional domains including multiple autonomous repression domains as well as two or three C-terminal nuclear receptor-interacting domains.[1] NCOR2/SMRT serves as a repressive coregulatory factor (corepressor) for multiple transcription factor pathways. In this regard, NCOR2/SMRT functions as a platform protein, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors.[3]


SMRT was initially cloned and characterized in the laboratory of Dr. Ronald M. Evans at the Salk Institute for Biological Studies.[1] In another early investigation into this molecule, similar findings were reported in a variant referred to as TRAC-1.[2]


Nuclear receptor co-repressor 2 has been shown to interact with:


  1. ^ a b c d Chen JD, Evans RM (1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature 377 (6548): 454–7. doi:10.1038/377454a0. PMID 7566127. 
  2. ^ a b c Sande S, Privalsky ML (1996). "Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors". Mol Endocrinol 10 (7): 813–25. doi:10.1210/me.10.7.813. PMID 8813722. 
  3. ^ Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM (1997). "Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase". Cell 89 (3): 373–80. doi:10.1016/S0092-8674(00)80218-4. PMID 9150137. 
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  5. ^ 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. 
  6. ^ Dotzlaw H, Moehren U, Mink S, Cato AC, Iñiguez Lluhí JA, Baniahmad A (2002). "The amino terminus of the human AR is target for corepressor action and antihormone agonism". Mol. Endocrinol. 16 (4): 661–73. doi:10.1210/me.16.4.661. PMID 11923464. 
  7. ^ a b Wong CW, Privalsky ML (1998). "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". J. Biol. Chem. 273 (42): 27695–702. doi:10.1074/jbc.273.42.27695. PMID 9765306. 
  8. ^ Huynh KD, Fischle W, Verdin E, Bardwell VJ (2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes Dev. 14 (14): 1810–23. doi:10.1101/gad.14.14.1810. PMC 316791. PMID 10898795. 
  9. ^ Deltour S, Guerardel C, Leprince D (1999). "Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: the case of HIC-1 and gammaFBP-B". Proc. Natl. Acad. Sci. U.S.A. 96 (26): 14831–6. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298. 
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  11. ^ a b Fischer DD, Cai R, Bhatia U, Asselbergs FA, Song C, Terry R, Trogani N, Widmer R, Atadja P, Cohen D (2002). "Isolation and characterization of a novel class II histone deacetylase, HDAC10". J. Biol. Chem. 277 (8): 6656–66. doi:10.1074/jbc.M108055200. PMID 11739383. 
  12. ^ a b Underhill C, Qutob MS, Yee SP, Torchia J (2000). "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1". J. Biol. Chem. 275 (51): 40463–70. doi:10.1074/jbc.M007864200. PMID 11013263. 
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  15. ^ a b Guenther MG, Yu J, Kao GD, Yen TJ, Lazar MA (2002). "Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex". Genes Dev. 16 (24): 3130–5. doi:10.1101/gad.1037502. PMC 187500. PMID 12502735. 
  16. ^ a b Guenther MG, Lane WS, Fischle W, Verdin E, Lazar MA, Shiekhattar R (2000). "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes Dev. 14 (9): 1048–57. doi:10.1101/gad.14.9.1048. PMC 316569. PMID 10809664. 
  17. ^ a b Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Mol. Cell 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. PMID 11804585. 
  18. ^ Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Mol. Cell 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417. 
  19. ^ a b c Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes Dev. 14 (1): 45–54. PMC 316335. PMID 10640275. 
  20. ^ Lyst MJ, Ekiert R, Ebert DH, Merusi C, Nowak J, Selfridge J, Guy J, Kastan NR, Robinson ND, de Lima Alves F, Rappsilber J, Greenberg ME, Bird A (July 2013). "Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor". Nat. Neurosci. 16 (7): 898–902. doi:10.1038/nn.3434. PMID 23770565. 
  21. ^ Sohn YC, Kwak E, Na Y, Lee JW, Lee SK (2001). "Silencing mediator of retinoid and thyroid hormone receptors and activating signal cointegrator-2 as transcriptional coregulators of the orphan nuclear receptor Nur77". J. Biol. Chem. 276 (47): 43734–9. doi:10.1074/jbc.M107208200. PMID 11559707. 
  22. ^ Kakizawa T, Miyamoto T, Ichikawa K, Takeda T, Suzuki S, Mori J, Kumagai M, Yamashita K, Hashizume K (2001). "Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor". J. Biol. Chem. 276 (13): 9720–5. doi:10.1074/jbc.M008531200. PMID 11134019. 
  23. ^ Shi Y, Hon M, Evans RM (2002). "The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2613–8. doi:10.1073/pnas.052707099. PMC 122396. PMID 11867749. 
  24. ^ Giangrande PH, Kimbrel EA, Edwards DP, McDonnell DP (2000). "The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding". Mol. Cell. Biol. 20 (9): 3102–15. doi:10.1128/MCB.20.9.3102-3115.2000. PMC 85605. PMID 10757795. 
  25. ^ Khan MM, Nomura T, Kim H, Kaul SC, Wadhwa R, Shinagawa T, Ichikawa-Iwata E, Zhong S, Pandolfi PP, Ishii S (2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Mol. Cell 7 (6): 1233–43. doi:10.1016/S1097-2765(01)00257-X. PMID 11430826. 
  26. ^ Hong SH, Yang Z, Privalsky ML (2001). "Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor with Its transcription factor partners, including the PML-retinoic acid receptor alpha oncoprotein found in human acute promyelocytic leukemia". Mol. Cell. Biol. 21 (21): 7172–82. doi:10.1128/MCB.21.21.7172-7182.2001. PMC 99892. PMID 11585900. 
  27. ^ Beatus P, Lundkvist J, Oberg C, Pedersen K, Lendahl U (2001). "The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity". Mech. Dev. 104 (1-2): 3–20. doi:10.1016/S0925-4773(01)00373-2. PMID 11404076. 
  28. ^ Zhou S, Hayward SD (2001). "Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex". Mol. Cell. Biol. 21 (18): 6222–32. doi:10.1128/MCB.21.18.6222-6232.2001. PMC 87339. PMID 11509665. 
  29. ^ Espinosa L, Inglés-Esteve J, Robert-Moreno A, Bigas A (2003). "IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways". Mol. Biol. Cell 14 (2): 491–502. doi:10.1091/mbc.E02-07-0404. PMC 149987. PMID 12589049. 
  30. ^ a b Takahashi S, McConnell MJ, Harigae H, Kaku M, Sasaki T, Melnick AM, Licht JD (2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood 103 (12): 4650–8. doi:10.1182/blood-2003-08-2759. PMID 14982881. 
  31. ^ Zhang J, Hug BA, Huang EY, Chen CW, Gelmetti V, Maccarana M, Minucci S, Pelicci PG, Lazar MA (2001). "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. 21 (1): 156–63. doi:10.1128/MCB.21.1.156-163.2001. PMC 88789. PMID 11113190. 
  32. ^ Dong S, Tweardy DJ (2002). "Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways". Blood 99 (8): 2637–46. doi:10.1182/blood.V99.8.2637. PMID 11929748. 
  33. ^ a b Hong SH, David G, Wong CW, Dejean A, Privalsky ML (1997). "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9028–33. doi:10.1073/pnas.94.17.9028. PMC 23013. PMID 9256429. 
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  37. ^ Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM (1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology 139 (10): 4197–204. doi:10.1210/endo.139.10.6218. PMID 9751500. 
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