Wikipedia

Nuclear receptor co-repressor 2

(Redirected from Silencing mediator for retinoid and thyroid-hormone receptor)

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.[5][6] NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT)[5] or T3 receptor-associating cofactor 1 (TRAC-1).[6]

NCOR2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNCOR2, CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau, TNRC14, TRAC, TRAC-1, TRAC1, nuclear receptor corepressor 2
External IDsOMIM: 600848; MGI: 1337080; HomoloGene: 31370; GeneCards: NCOR2; OMA:NCOR2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9612

20602

Ensembl

ENSG00000196498

ENSMUSG00000029478

UniProt

Q9Y618

Q9WU42

RefSeq (mRNA)

NM_006312
NM_001077261
NM_001206654

NM_001253904
NM_001253905
NM_011424

RefSeq (protein)

NP_001070729
NP_001193583
NP_006303
NP_001193583.1

NP_001240833
NP_001240834
NP_035554

Location (UCSC)Chr 12: 124.32 – 124.57 MbChr 5: 125.02 – 125.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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.[5] 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.[7]

Family

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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.[8]

Discovery

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SMRT was initially cloned and characterized in the laboratory of Dr. Ronald M. Evans at the Salk Institute for Biological Studies.[5] In another early investigation into this molecule, similar findings were reported in a variant referred to as TRAC-1.[6]

Interactions

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

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196498 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029478 – 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. ^ 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. Bibcode:1995Natur.377..454C. doi:10.1038/377454a0. PMID 7566127. S2CID 4361329.
  6. ^ 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/mend.10.7.8813722. PMID 8813722.
  7. ^ 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. S2CID 14686941.
  8. ^ UniProt Nuclear receptor corepressors family Page accessed June 26, 2016
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
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  14. ^ 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. Bibcode:1999PNAS...9614831D. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298.
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  25. ^ 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. PMC 3786392. PMID 23770565.
  26. ^ 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.
  27. ^ 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.
  28. ^ 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. Bibcode:2002PNAS...99.2613S. doi:10.1073/pnas.052707099. PMC 122396. PMID 11867749.
  29. ^ 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.
  30. ^ 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.
  31. ^ 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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Further reading

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