Nuclear receptor co-repressor 2

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NCOR2
Protein NCOR2 PDB 1xc5.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NCOR2, CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau, TNRC14, TRAC, TRAC-1, TRAC1, nuclear receptor corepressor 2
External IDs OMIM: 600848 MGI: 1337080 HomoloGene: 31370 GeneCards: 9612
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
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006312
NM_001077261
NM_001206654

NM_001253904
NM_001253905
NM_011424

RefSeq (protein)

NP_001070729.2
NP_001193583.1
NP_006303.4
NP_001193583.1

NP_001240833.1
NP_001240834.1

Location (UCSC) Chr 12: 124.32 – 124.57 Mb Chr 5: 125.02 – 125.18 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

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]

Function[edit]

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]

Family[edit]

It is a member of the family of nuclear receptor corepressors; the other human protein that is a member of that family is Nuclear receptor co-repressor 1.[4]

Discovery[edit]

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]

Interactions[edit]

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

References[edit]

  1. ^ a b c d Chen JD, Evans RM (October 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 (July 1996). "Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors". Molecular Endocrinology 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 (May 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. 
  4. ^ UniProt Nuclear receptor corepressors family Page accessed June 26, 2016
  5. ^ Liao G, Chen LY, Zhang A, Godavarthy A, Xia F, Ghosh JC, Li H, Chen JD (February 2003). "Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT". The Journal of Biological Chemistry 278 (7): 5052–61. doi:10.1074/jbc.M206374200. PMID 12441355. 
  6. ^ Song LN, Coghlan M, Gelmann EP (January 2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Molecular Endocrinology 18 (1): 70–85. doi:10.1210/me.2003-0189. PMID 14593076. 
  7. ^ Dotzlaw H, Moehren U, Mink S, Cato AC, Iñiguez Lluhí JA, Baniahmad A (April 2002). "The amino terminus of the human AR is target for corepressor action and antihormone agonism". Molecular Endocrinology 16 (4): 661–73. doi:10.1210/me.16.4.661. PMID 11923464. 
  8. ^ a b Wong CW, Privalsky ML (October 1998). "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". The Journal of Biological Chemistry 273 (42): 27695–702. doi:10.1074/jbc.273.42.27695. PMID 9765306. 
  9. ^ Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes & Development 14 (14): 1810–23. doi:10.1101/gad.14.14.1810. PMC 316791. PMID 10898795. 
  10. ^ Deltour S, Guerardel C, Leprince D (December 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". Proceedings of the National Academy of Sciences of the United States of America 96 (26): 14831–6. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298. 
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  12. ^ a b Fischer DD, Cai R, Bhatia U, Asselbergs FA, Song C, Terry R, Trogani N, Widmer R, Atadja P, Cohen D (February 2002). "Isolation and characterization of a novel class II histone deacetylase, HDAC10". The Journal of Biological Chemistry 277 (8): 6656–66. doi:10.1074/jbc.M108055200. PMID 11739383. 
  13. ^ a b Underhill C, Qutob MS, Yee SP, Torchia J (December 2000). "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1". The Journal of Biological Chemistry 275 (51): 40463–70. doi:10.1074/jbc.M007864200. PMID 11013263. 
  14. ^ a b c Li J, Wang J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J (August 2000). "Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3". The EMBO Journal 19 (16): 4342–50. doi:10.1093/emboj/19.16.4342. PMC 302030. PMID 10944117. 
  15. ^ a b Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (March 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". The EMBO Journal 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926. 
  16. ^ a b Guenther MG, Yu J, Kao GD, Yen TJ, Lazar MA (December 2002). "Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex". Genes & Development 16 (24): 3130–5. doi:10.1101/gad.1037502. PMC 187500. PMID 12502735. 
  17. ^ a b Guenther MG, Lane WS, Fischle W, Verdin E, Lazar MA, Shiekhattar R (May 2000). "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes & Development 14 (9): 1048–57. doi:10.1101/gad.14.9.1048. PMC 316569. PMID 10809664. 
  18. ^ a b Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. PMID 11804585. 
  19. ^ Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (September 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417. 
  20. ^ a b c Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development 14 (1): 45–54. PMC 316335. PMID 10640275. 
  21. ^ 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". Nature Neuroscience 16 (7): 898–902. doi:10.1038/nn.3434. PMID 23770565. 
  22. ^ Sohn YC, Kwak E, Na Y, Lee JW, Lee SK (November 2001). "Silencing mediator of retinoid and thyroid hormone receptors and activating signal cointegrator-2 as transcriptional coregulators of the orphan nuclear receptor Nur77". The Journal of Biological Chemistry 276 (47): 43734–9. doi:10.1074/jbc.M107208200. PMID 11559707. 
  23. ^ Kakizawa T, Miyamoto T, Ichikawa K, Takeda T, Suzuki S, Mori J, Kumagai M, Yamashita K, Hashizume K (March 2001). "Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor". The Journal of Biological Chemistry 276 (13): 9720–5. doi:10.1074/jbc.M008531200. PMID 11134019. 
  24. ^ Shi Y, Hon M, Evans RM (March 2002). "The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling". Proceedings of the National Academy of Sciences of the United States of America 99 (5): 2613–8. doi:10.1073/pnas.052707099. PMC 122396. PMID 11867749. 
  25. ^ Giangrande PH, Kimbrel EA, Edwards DP, McDonnell DP (May 2000). "The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding". Molecular and Cellular Biology 20 (9): 3102–15. doi:10.1128/MCB.20.9.3102-3115.2000. PMC 85605. PMID 10757795. 
  26. ^ Khan MM, Nomura T, Kim H, Kaul SC, Wadhwa R, Shinagawa T, Ichikawa-Iwata E, Zhong S, Pandolfi PP, Ishii S (June 2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Molecular Cell 7 (6): 1233–43. doi:10.1016/S1097-2765(01)00257-X. PMID 11430826. 
  27. ^ Hong SH, Yang Z, Privalsky ML (November 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". Molecular and Cellular Biology 21 (21): 7172–82. doi:10.1128/MCB.21.21.7172-7182.2001. PMC 99892. PMID 11585900. 
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  29. ^ Zhou S, Hayward SD (September 2001). "Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex". Molecular and Cellular Biology 21 (18): 6222–32. doi:10.1128/MCB.21.18.6222-6232.2001. PMC 87339. PMID 11509665. 
  30. ^ Espinosa L, Inglés-Esteve J, Robert-Moreno A, Bigas A (February 2003). "IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways". Molecular Biology of the Cell 14 (2): 491–502. doi:10.1091/mbc.E02-07-0404. PMC 149987. PMID 12589049. 
  31. ^ a b Takahashi S, McConnell MJ, Harigae H, Kaku M, Sasaki T, Melnick AM, Licht JD (June 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. 
  32. ^ Zhang J, Hug BA, Huang EY, Chen CW, Gelmetti V, Maccarana M, Minucci S, Pelicci PG, Lazar MA (January 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Molecular and Cellular Biology 21 (1): 156–63. doi:10.1128/MCB.21.1.156-163.2001. PMC 88789. PMID 11113190. 
  33. ^ Dong S, Tweardy DJ (April 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. 
  34. ^ a b Hong SH, David G, Wong CW, Dejean A, Privalsky ML (August 1997). "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America 94 (17): 9028–33. doi:10.1073/pnas.94.17.9028. PMC 23013. PMID 9256429. 
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Further reading[edit]


External links[edit]