Nuclear receptor co-repressor 2

Nuclear receptor co-repressor 2
Nuclear receptor corepressor 2

PDB rendering based on 1xc5.
Symbols NCOR2; CTG26; FLJ25011; N-CoR2; SMAP270; SMRT; SMRTE; SMRTE-tau; TNRC14; TRAC; TRAC-1; TRAC1
External IDs OMIM600848 MGI1337080 HomoloGene31370 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 n/a
RefSeq (mRNA) NM_001077261.3 NM_011424.2
RefSeq (protein) NP_001070729.2 NP_035554.2
Location (UCSC) Chr 12:
124.81 – 125.05 Mb
Chr 5:
125.5 – 125.66 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 Thyroid hormone receptor beta,[4][5][6] Retinoic acid receptor alpha,[7][8] HDAC1,[9][10] Nerve Growth factor IB,[11] Zinc finger and BTB domain-containing protein 16,[8][12][13] SIN3A,[14][15] BCL6,[13][16][17] SNW1,[18][19] Androgen receptor,[20][21][22] Peroxisome proliferator-activated receptor delta,[23] C-Fos,[24] POU2F1,[25] Histone deacetylase 5,[15] HDAC10,[9] RELA,[24][26] RBPJ,[27][28] TBL1X,[14][29][30][31] RUNX1T1,[12][32] HDAC4,[15][33] Progesterone receptor,[34] HDAC3,[10][14][29][30][31][33][35] SPEN,[36] Serum response factor,[24] C-jun,[24] Calcitriol receptor[5][37] and Promyelocytic leukemia protein.[38][39]


  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. 
  4. ^ Liu, Y; Takeshita A, Misiti S, Chin W W, Yen P M (Oct. 1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology (UNITED STATES) 139 (10): 4197–204. doi:10.1210/en.139.10.4197. ISSN 0013-7227. PMID 9751500. 
  5. ^ a b Tagami, T; Lutz W H, Kumar R, Jameson J L (Dec. 1998). "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochem. Biophys. Res. Commun. (UNITED STATES) 253 (2): 358–63. doi:10.1006/bbrc.1998.9799. ISSN 0006-291X. PMID 9878542. 
  6. ^ Ando, S; Sarlis N J, Krishnan J, Feng X, Refetoff S, Zhang M Q, Oldfield E H, Yen P M (Sep. 2001). "Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance". Mol. Endocrinol. (United States) 15 (9): 1529–38. doi:10.1210/me.15.9.1529. ISSN 0888-8809. PMID 11518802. 
  7. ^ Dong, Shuo; Tweardy David J (Apr. 2002). "Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways". Blood (United States) 99 (8): 2637–46. doi:10.1182/blood.V99.8.2637. ISSN 0006-4971. PMID 11929748. 
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  9. ^ a b Fischer, Denise D; Cai Richard, Bhatia Umesh, Asselbergs Fred A M, Song Chuanzheng, Terry Robert, Trogani Nancy, Widmer Roland, Atadja Peter, Cohen Dalia (Feb. 2002). "Isolation and characterization of a novel class II histone deacetylase, HDAC10". J. Biol. Chem. (United States) 277 (8): 6656–66. doi:10.1074/jbc.M108055200. ISSN 0021-9258. PMID 11739383. 
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  11. ^ Sohn, Y C; Kwak E, Na Y, Lee J W, Lee S K (Nov. 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. (United States) 276 (47): 43734–9. doi:10.1074/jbc.M107208200. ISSN 0021-9258. PMID 11559707. 
  12. ^ a b Takahashi, Shinichiro; McConnell Melanie J, Harigae Hideo, Kaku Mitsuo, Sasaki Takeshi, Melnick Ari M, Licht Jonathan D (Jun. 2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood (United States) 103 (12): 4650–8. doi:10.1182/blood-2003-08-2759. ISSN 0006-4971. PMID 14982881. 
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  18. ^ Zhou, S; Fujimuro M, Hsieh J J, Chen L, Hayward S D (Feb. 2000). "A Role for SKIP in EBNA2 Activation of CBF1-Repressed Promoters". J. Virol. (UNITED STATES) 74 (4): 1939–47. doi:10.1128/JVI.74.4.1939-1947.2000. ISSN 0022-538X. PMC 111672. PMID 10644367. 
  19. ^ Zhou, S; Fujimuro M, Hsieh J J, Chen L, Miyamoto A, Weinmaster G, Hayward S D (Apr. 2000). "SKIP, a CBF1-Associated Protein, Interacts with the Ankyrin Repeat Domain of NotchIC To Facilitate NotchIC Function". Mol. Cell. Biol. (UNITED STATES) 20 (7): 2400–10. doi:10.1128/MCB.20.7.2400-2410.2000. ISSN 0270-7306. PMC 85419. PMID 10713164. 
  20. ^ Liao, Guoqing; Chen Liuh-Yow, Zhang Aihua, Godavarthy Aparna, Xia Fang, Ghosh Jagadish Chandra, Li Hui, Chen J Don (Feb. 2003). "Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT". J. Biol. Chem. (United States) 278 (7): 5052–61. doi:10.1074/jbc.M206374200. ISSN 0021-9258. PMID 12441355. 
  21. ^ Song, Liang-Nian; Coghlan Meghan, Gelmann Edward P (Jan. 2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. (United States) 18 (1): 70–85. doi:10.1210/me.2003-0189. ISSN 0888-8809. PMID 14593076. 
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