From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
NCOR2
Available structures
PDB Ortholog search:
PDBe
RCSB List of PDB id codes
2RT5 ,
4OAR ,
2L5G ,
2LTP ,
1KKQ ,
3R2A ,
2ODD ,
4A69 ,
3R29 ,
1XC5 ,
1R2B ,%%s
1KKQ ,
1R2B ,
1XC5 ,
2GPV ,
2LTP ,
3R29 ,
3R2A ,
4A69 ,
2L5G ,
2ODD ,
2RT5 ,
4OAR
Identifiers
Aliases
NCOR2 , CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau, TNRC14, TRAC, TRAC-1, TRAC1, nuclear receptor corepressor 2External IDs
OMIM :
600848
MGI :
1337080
HomoloGene :
31370
GeneCards :
NCOR2
Wikidata
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]
Function
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
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
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
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]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000196498 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000029478 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
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.
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7566127 .
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^
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b
c Sande S, Privalsky ML (July 1996).
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^
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b
c Li J, Wang J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J (August 2000).
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a
b Guenther MG, Yu J, Kao GD, Yen TJ, Lazar MA (December 2002).
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^
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.
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^
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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.
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^ 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.
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^
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.
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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.
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^ 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.
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^ 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.
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PMID
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^ Shi Y, Hon M, Evans RM (March 2002).
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^ 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.
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^ 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.
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^ Espinosa L, Inglés-Esteve J, Robert-Moreno A, Bigas A (February 2003).
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^
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b Takahashi S, McConnell MJ, Harigae H, Kaku M, Sasaki T, Melnick AM, Licht JD (June 2004).
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^
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b Hong SH, David G, Wong CW, Dejean A, Privalsky ML (August 1997).
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b 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.
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Further reading
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 .
External links