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]
Quick Facts NCOR2, Available structures ...
NCOR2 |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/4/4b/Protein_NCOR2_PDB_1xc5.png/250px-Protein_NCOR2_PDB_1xc5.png) |
Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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2RT5, 4OAR, 2L5G, 2LTP, 1KKQ, 3R2A, 2ODD, 4A69, 3R29, 1XC5, 1R2B,%%s1KKQ, 1R2B, 1XC5, 2GPV, 2LTP, 3R29, 3R2A, 4A69, 2L5G, 2ODD, 2RT5, 4OAR |
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Identifiers |
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Aliases | NCOR2, CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau, TNRC14, TRAC, TRAC-1, TRAC1, nuclear receptor corepressor 2 |
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External IDs | OMIM: 600848; MGI: 1337080; HomoloGene: 31370; GeneCards: NCOR2; OMA:NCOR2 - orthologs |
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Wikidata |
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Close
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]
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]
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]
Nuclear receptor co-repressor 2 has been shown to interact with:
- AR,[9][10][11]
- BCL6,[12][13][14]
- C-Fos,[15]
- C-jun,[15]
- HDAC1,[16][17]
- HDAC3,[17][18][19][20][21][22][23]
- HDAC4,[22][24]
- HDAC5,[24]
- HDAC10,[16]
- MeCP2,[25]
- NR4A1,[26]
- POU2F1,[27]
- PPARD,[28]
- PGR,[29]
- PML[30][31]
- RBPJ,[32][33]
- RELA,[15][34]
- RUNX1T1,[35][36]
- RARA,[37][38]
- SIN3A,[18][24]
- SNW1,[39][40]
- SPEN,[41]
- SRF,[15]
- TBL1X,[18][19][20][21]
- THRB,[42][43][44]
- VDR,[43][45] and
- ZBTB16.[12][35][38]
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.
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.
Tagami T, Lutz WH, Kumar R, Jameson JL (December 1998). "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochemical and Biophysical Research Communications. 253 (2): 358–63. doi:10.1006/bbrc.1998.9799. PMID 9878542.
Puccetti E, Obradovic D, Beissert T, Bianchini A, Washburn B, Chiaradonna F, Boehrer S, Hoelzer D, Ottmann OG, Pelicci PG, Nervi C, Ruthardt M (December 2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Research. 62 (23): 7050–8. PMID 12460926.
- Hörlein AJ, Näär AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamei Y, Söderström M, Glass CK (October 1995). "Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor". Nature. 377 (6548): 397–404. Bibcode:1995Natur.377..397H. doi:10.1038/377397a0. PMID 7566114. S2CID 4230850.
- 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.
- 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.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (July 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics. 100 (1): 114–22. doi:10.1007/s004390050476. PMID 9225980. S2CID 25999127.
- 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. Bibcode:1997PNAS...94.9028H. doi:10.1073/pnas.94.17.9028. PMC 23013. PMID 9256429.
- Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (August 1997). "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300". Cell. 90 (3): 569–80. doi:10.1016/S0092-8674(00)80516-4. PMID 9267036. S2CID 15284825.
- Lin RJ, Nagy L, Inoue S, Shao W, Miller WH, Evans RM (February 1998). "Role of the histone deacetylase complex in acute promyelocytic leukaemia". Nature. 391 (6669): 811–4. Bibcode:1998Natur.391..811L. doi:10.1038/35895. PMID 9486654. S2CID 4383951.
- Laherty CD, Billin AN, Lavinsky RM, Yochum GS, Bush AC, Sun JM, Mullen TM, Davie JR, Rose DW, Glass CK, Rosenfeld MG, Ayer DE, Eisenman RN (July 1998). "SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors". Molecular Cell. 2 (1): 33–42. doi:10.1016/S1097-2765(00)80111-2. PMID 9702189.
- Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM (October 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.
- 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.
- Ordentlich P, Downes M, Xie W, Genin A, Spinner NB, Evans RM (March 1999). "Unique forms of human and mouse nuclear receptor corepressor SMRT". Proceedings of the National Academy of Sciences of the United States of America. 96 (6): 2639–44. Bibcode:1999PNAS...96.2639O. doi:10.1073/pnas.96.6.2639. PMC 15821. PMID 10077563.
- Park EJ, Schroen DJ, Yang M, Li H, Li L, Chen JD (March 1999). "SMRTe, a silencing mediator for retinoid and thyroid hormone receptors-extended isoform that is more related to the nuclear receptor corepressor". Proceedings of the National Academy of Sciences of the United States of America. 96 (7): 3519–24. Bibcode:1999PNAS...96.3519P. doi:10.1073/pnas.96.7.3519. PMC 22325. PMID 10097068.
- Nguyen TA, Hoivik D, Lee JE, Safe S (July 1999). "Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex". Archives of Biochemistry and Biophysics. 367 (2): 250–7. doi:10.1006/abbi.1999.1282. PMID 10395741.
- Bailey P, Downes M, Lau P, Harris J, Chen SL, Hamamori Y, Sartorelli V, Muscat GE (July 1999). "The nuclear receptor corepressor N-CoR regulates differentiation: N-CoR directly interacts with MyoD". Molecular Endocrinology. 13 (7): 1155–68. doi:10.1210/mend.13.7.0305. PMID 10406466.
- Kao HY, Downes M, Ordentlich P, Evans RM (January 2000). "Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression". Genes & Development. 14 (1): 55–66. doi:10.1101/gad.14.1.55. PMC 316336. PMID 10640276.
- Zhou S, Fujimuro M, Hsieh JJ, Chen L, Miyamoto A, Weinmaster G, Hayward SD (April 2000). "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function". Molecular and Cellular Biology. 20 (7): 2400–10. doi:10.1128/MCB.20.7.2400-2410.2000. PMC 85419. PMID 10713164.
- Lee SK, Kim JH, Lee YC, Cheong J, Lee JW (April 2000). "Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor". The Journal of Biological Chemistry. 275 (17): 12470–4. doi:10.1074/jbc.275.17.12470. PMID 10777532.
- 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.
- Grozinger CM, Schreiber SL (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7835–40. Bibcode:2000PNAS...97.7835G. doi:10.1073/pnas.140199597. PMC 16631. PMID 10869435.