Nuclear receptor co-repressor 1

Nuclear receptor corepressor 1
Rendering based on PDB 2EQR.
Available structures PDB 2EQR, 3H52, 3KMZ, 3N00
Identifiers
Symbols	NCOR1; KIAA1047; MGC104216; N-CoR; N-CoR1; TRAC1; hN-CoR
External IDs	OMIM: 600849 MGI: 1349717 HomoloGene: 38166 GeneCards: NCOR1 Gene
Gene Ontology Molecular function • sequence-specific DNA binding transcription factor activity • transcription corepressor activity • transcription corepressor activity • protein binding • protein domain specific binding • histone deacetylase regulator activity • histone deacetylase binding • sequence-specific DNA binding • transcription regulatory region DNA binding • retinoid X receptor binding • thyroid hormone receptor binding Cellular component • histone deacetylase complex • nuclear chromatin • nucleus • nucleoplasm • transcription factor complex • cytoplasm • spindle microtubule • transcriptional repressor complex • nuclear part Biological process • negative regulation of transcription from RNA polymerase II promoter • CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation • transcription from RNA polymerase II promoter • negative regulation of phosphatidylinositol 3-kinase cascade • chromatin modification • cerebellum development • thalamus development • positive regulation of histone deacetylation • circadian regulation of gene expression • regulation of multicellular organism growth • cholesterol homeostasis • cellular lipid metabolic process • negative regulation of JNK cascade • spindle assembly • definitive erythrocyte differentiation • regulation of glycolysis by negative regulation of transcription from an RNA polymerase II promoter • regulation of lipid transport by negative regulation of transcription from an RNA polymerase II promoter • regulation of fatty acid transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9611	20185
Ensembl	ENSG00000141027	ENSMUSG00000018501
UniProt	O75376	n/a
RefSeq (mRNA)	NM_001190438.1	NM_011308.2
RefSeq (protein)	NP_001177367.1	NP_035438.2
Location (UCSC)	Chr 17: 15.93 – 16.12 Mb	Chr 11: 62.13 – 62.27 Mb
PubMed search	[1]	[2]

The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the NCOR1 gene.^[1][2]

NCOR1 is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains. In addition, NCOR1 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR1 assists nuclear receptors in the down regulation of DNA expression.^[1][3]

Loss of function of this protein significantly increases the strength and power of mouse muscles.^[4]

Interactions

Nuclear receptor co-repressor 1 has been shown to interact with HDAC9,^[5] CHD1,^[6] HDAC7A,^[7] MAP3K7IP2,^[8] Glucocorticoid receptor,^[9][10] MECP2,^[11] Peroxisome proliferator-activated receptor alpha,^[12] HEY2,^[13] Histone deacetylase 5,^[14][15] TBL1XR1,^[14][16][17] TBL1X,^{[14][17][18][19]} HDAC3,^{[7][14][16][17][18][20][21]} ZBTB33,^[16] Retinoic acid receptor alpha,^[12][22] SAP30,^[21][23] Androgen receptor,^{[24][25][26][27]} Retinoic acid receptor gamma,^[12] RUNX1T1,^[28][29] HDAC4,^[15][20] GPS2,^[14][16][17] Calcitriol receptor^[30][31] and Promyelocytic leukemia protein.^[32]

References

1. ^ ^{a b} 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. doi:10.1038/377397a0. PMID 7566114. 
2. ^ Wang J, Hoshino T, Redner RL, Kajigaya S, Liu JM (September 1998). "ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex". Proc. Natl. Acad. Sci. U.S.A. 95 (18): 10860–5. PMC 27986. PMID 9724795. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27986. 
3. ^ Wang J, Hoshino T, Redner RL, Kajigaya S, Liu JM (1998). "ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex". Proc Natl Acad Sci USA 95 (18): 10860–5. doi:10.1073/pnas.95.18.10860. PMC 27986. PMID 9724795. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27986. 
4. ^ Yamamoto H, Williams EG, Mouchiroud L, Cantó C, Fan W, Downes M, Héligon C, Barish GD, Desvergne B, Evans RM, Schoonjans E, Auwerx J (2011). "NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function". Cell 147 (4): 827–839. 
5. ^ Petrie, Kevin; Guidez Fabien, Howell Louise, Healy Lyn, Waxman Samuel, Greaves Mel, Zelent Arthur (May. 2003). "The histone deacetylase 9 gene encodes multiple protein isoforms". J. Biol. Chem. (United States) 278 (18): 16059–72. doi:10.1074/jbc.M212935200. ISSN 0021-9258. PMID 12590135. 
6. ^ Tai, Helen H; Geisterfer Margit, Bell John C, Moniwa Mariko, Davie James R, Boucher Lorrie, McBurney Michael W (Aug. 2003). "CHD1 associates with NCoR and histone deacetylase as well as with RNA splicing proteins". Biochem. Biophys. Res. Commun. (United States) 308 (1): 170–6. doi:10.1016/S0006-291X(03)01354-8. ISSN 0006-291X. PMID 12890497. 
7. ^ ^{a b} Fischle, W; Dequiedt F, Fillion M, Hendzel M J, Voelter W, Verdin E (Sep. 2001). "Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo". J. Biol. Chem. (United States) 276 (38): 35826–35. doi:10.1074/jbc.M104935200. ISSN 0021-9258. PMID 11466315. 
8. ^ Baek, Sung Hee; Ohgi Kenneth A, Rose David W, Koo Edward H, Glass Christopher K, Rosenfeld Michael G (Jul. 2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell (United States) 110 (1): 55–67. doi:10.1016/S0092-8674(02)00809-7. ISSN 0092-8674. PMID 12150997. 
9. ^ Stevens, Adam; Garside Helen, Berry Andrew, Waters Charlotte, White Anne, Ray David (May. 2003). "Dissociation of steroid receptor coactivator 1 and nuclear receptor corepressor recruitment to the human glucocorticoid receptor by modification of the ligand-receptor interface: the role of tyrosine 735". Mol. Endocrinol. (United States) 17 (5): 845–59. doi:10.1210/me.2002-0320. ISSN 0888-8809. PMID 12569182. 
10. ^ Schulz, Martin; Eggert Martin, Baniahmad Aria, Dostert Anja, Heinzel Thorsten, Renkawitz Rainer (Jul. 2002). "RU486-induced glucocorticoid receptor agonism is controlled by the receptor N terminus and by corepressor binding". J. Biol. Chem. (United States) 277 (29): 26238–43. doi:10.1074/jbc.M203268200. ISSN 0021-9258. PMID 12011091. 
11. ^ Kokura, K; Kaul S C, Wadhwa R, Nomura T, Khan M M, Shinagawa T, Yasukawa T, Colmenares C, Ishii S (Sep. 2001). "The Ski protein family is required for MeCP2-mediated transcriptional repression". J. Biol. Chem. (United States) 276 (36): 34115–21. doi:10.1074/jbc.M105747200. ISSN 0021-9258. PMID 11441023. 
12. ^ ^{a b c} Dowell, P; Ishmael J E, Avram D, Peterson V J, Nevrivy D J, Leid M (May. 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". J. Biol. Chem. (UNITED STATES) 274 (22): 15901–7. doi:10.1074/jbc.274.22.15901. ISSN 0021-9258. PMID 10336495. 
13. ^ Iso, T; Sartorelli V, Poizat C, Iezzi S, Wu H Y, Chung G, Kedes L, Hamamori Y (Sep. 2001). "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling". Mol. Cell. Biol. (United States) 21 (17): 6080–9. doi:10.1128/MCB.21.17.6080-6089.2001. ISSN 0270-7306. PMC 87325. PMID 11486045. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87325. 
14. ^ ^{a b c d e} Zhang, Jinsong; Kalkum Markus, Chait Brian T, Roeder Robert G (Mar. 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Mol. Cell (United States) 9 (3): 611–23. doi:10.1016/S1097-2765(02)00468-9. ISSN 1097-2765. PMID 11931768. 
15. ^ ^{a b} Huang, E Y; Zhang J, Miska E A, Guenther M G, Kouzarides T, Lazar M A (Jan. 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes Dev. (UNITED STATES) 14 (1): 45–54. ISSN 0890-9369. PMC 316335. PMID 10640275. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316335. 
16. ^ ^{a b c d} Yoon, Ho-Geun; Chan Doug W, Reynolds Albert B, Qin Jun, Wong Jiemin (Sep. 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Mol. Cell (United States) 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. ISSN 1097-2765. PMID 14527417. 
17. ^ ^{a b c d} Yoon, Ho-Geun; Chan Doug W, Huang Zhi-Qing, Li Jiwen, Fondell Joseph D, Qin Jun, Wong Jiemin (Mar. 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". EMBO J. (England) 22 (6): 1336–46. doi:10.1093/emboj/cdg120. ISSN 0261-4189. PMC 151047. PMID 12628926. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151047. 
18. ^ ^{a b} Li, J; Wang J, Wang J, Nawaz Z, Liu J M, Qin J, Wong J (Aug. 2000). "Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3". EMBO J. (ENGLAND) 19 (16): 4342–50. doi:10.1093/emboj/19.16.4342. ISSN 0261-4189. PMC 302030. PMID 10944117. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=302030. 
19. ^ Guenther, M G; Lane W S, Fischle W, Verdin E, Lazar M A, Shiekhattar R (May. 2000). "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes Dev. (UNITED STATES) 14 (9): 1048–57. ISSN 0890-9369. PMC 316569. PMID 10809664. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316569. 
20. ^ ^{a b} Fischle, Wolfgang; Dequiedt Franck, Hendzel Michael J, Guenther Matthew G, Lazar Mitchell A, Voelter Wolfgang, Verdin Eric (Jan. 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Mol. Cell (United States) 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. ISSN 1097-2765. PMID 11804585. 
21. ^ ^{a b} Underhill, C; Qutob M S, Yee S P, Torchia J (Dec. 2000). "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1". J. Biol. Chem. (UNITED STATES) 275 (51): 40463–70. doi:10.1074/jbc.M007864200. ISSN 0021-9258. PMID 11013263. 
22. ^ Guidez, F; Ivins S, Zhu J, Söderström M, Waxman S, Zelent A (Apr. 1998). "Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia". Blood (UNITED STATES) 91 (8): 2634–42. ISSN 0006-4971. PMID 9531570. 
23. ^ Laherty, C D; Billin A N, Lavinsky R M, Yochum G S, Bush A C, Sun J M, Mullen T M, Davie J R, Rose D W, Glass C K, Rosenfeld M G, Ayer D E, Eisenman R N (Jul. 1998). "SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors". Mol. Cell (UNITED STATES) 2 (1): 33–42. doi:10.1016/S1097-2765(00)80111-2. ISSN 1097-2765. PMID 9702189. 
24. ^ Masiello, David; Chen Shao-Yong, Xu Youyuan, Verhoeven Manon C, Choi Eunis, Hollenberg Anthony N, Balk Steven P (Oct. 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Mol. Endocrinol. (United States) 18 (10): 2388–401. doi:10.1210/me.2003-0436. ISSN 0888-8809. PMID 15256534. 
25. ^ 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. 
26. ^ Cheng, Shinta; Brzostek Sabrina, Lee Suzanne R, Hollenberg Anthony N, Balk Steven P (Jul. 2002). "Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor". Mol. Endocrinol. (United States) 16 (7): 1492–501. doi:10.1210/me.16.7.1492. ISSN 0888-8809. PMID 12089345. 
27. ^ Hodgson, Myles C; Astapova Inna, Cheng Shinta, Lee Larissa J, Verhoeven Manon C, Choi Eunis, Balk Steven P, Hollenberg Anthony N (Feb. 2005). "The androgen receptor recruits nuclear receptor CoRepressor (N-CoR) in the presence of mifepristone via its N and C termini revealing a novel molecular mechanism for androgen receptor antagonists". J. Biol. Chem. (United States) 280 (8): 6511–9. doi:10.1074/jbc.M408972200. ISSN 0021-9258. PMID 15598662. 
28. ^ Amann, J M; Nip J, Strom D K, Lutterbach B, Harada H, Lenny N, Downing J R, Meyers S, Hiebert S W (Oct. 2001). "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain". Mol. Cell. Biol. (United States) 21 (19): 6470–83. doi:10.1128/MCB.21.19.6470-6483.2001. ISSN 0270-7306. PMC 99794. PMID 11533236. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99794. 
29. ^ Zhang, J; Hug B A, Huang E Y, Chen C W, Gelmetti V, Maccarana M, Minucci S, Pelicci P G, Lazar M A (Jan. 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. (UNITED STATES) 21 (1): 156–63. doi:10.1128/MCB.21.1.156-163.2001. ISSN 0270-7306. PMC 88789. PMID 11113190. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=88789. 
30. ^ Puccetti, Elena; Obradovic Darja, Beissert Tim, Bianchini Andrea, Washburn Birgit, Chiaradonna Ferdinando, Boehrer Simone, Hoelzer Dieter, Ottmann Oliver Gerhard, Pelicci Pier Giuseppe, Nervi Clara, Ruthardt Martin (Dec. 2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Res. (United States) 62 (23): 7050–8. ISSN 0008-5472. PMID 12460926. 
31. ^ 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. 
32. ^ Khan, M M; Nomura T, Kim H, Kaul S C, Wadhwa R, Shinagawa T, Ichikawa-Iwata E, Zhong S, Pandolfi P P, Ishii S (Jun. 2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Mol. Cell (United States) 7 (6): 1233–43. doi:10.1016/S1097-2765(01)00257-X. ISSN 1097-2765. PMID 11430826. 

Further reading

• Minucci S, Pelicci PG (1999). "Retinoid receptors in health and disease: co-regulators and the chromatin connection.". Semin. Cell Dev. Biol. 10 (2): 215–25. doi:10.1006/scdb.1999.0303. PMID 10441075. 
• Downes M, Burke LJ, Bailey PJ, Muscat GE (1997). "Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbA alpha and RVR: physical association is dependent on the E region of the orphan receptors.". Nucleic Acids Res. 24 (22): 4379–86. doi:10.1093/nar/24.22.4379. PMC 146280. PMID 8948627. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=146280. 
• Tagami T, Madison LD, Nagaya T, Jameson JL (1997). "Nuclear receptor corepressors activate rather than suppress basal transcription of genes that are negatively regulated by thyroid hormone.". Mol. Cell. Biol. 17 (5): 2642–8. PMC 232114. PMID 9111334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232114. 
• Zamir I, Dawson J, Lavinsky RM, et al. (1998). "Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex.". Proc. Natl. Acad. Sci. U.S.A. 94 (26): 14400–5. doi:10.1073/pnas.94.26.14400. PMC 24996. PMID 9405624. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24996. 
• Burke LJ, Downes M, Laudet V, Muscat GE (1998). "Identification and characterization of a novel corepressor interaction region in RVR and Rev-erbA alpha.". Mol. Endocrinol. 12 (2): 248–62. doi:10.1210/me.12.2.248. PMID 9482666. 
• Guidez F, Ivins S, Zhu J, et al. (1998). "Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia.". Blood 91 (8): 2634–42. PMID 9531570. 
• Kao HY, Ordentlich P, Koyano-Nakagawa N, et al. (1998). "A histone deacetylase corepressor complex regulates the Notch signal transduction pathway.". Genes Dev. 12 (15): 2269–77. doi:10.1101/gad.12.15.2269. PMC 317043. PMID 9694793. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317043. 
• Laherty CD, Billin AN, Lavinsky RM, et al. (1998). "SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors.". Mol. Cell 2 (1): 33–42. doi:10.1016/S1097-2765(00)80111-2. PMID 9702189. 
• Wang J, Hoshino T, Redner RL, et al. (1998). "ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex.". Proc. Natl. Acad. Sci. U.S.A. 95 (18): 10860–5. doi:10.1073/pnas.95.18.10860. PMC 27986. PMID 9724795. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27986. 
• Ordentlich P, Downes M, Xie W, et al. (1999). "Unique forms of human and mouse nuclear receptor corepressor SMRT.". Proc. Natl. Acad. Sci. U.S.A. 96 (6): 2639–44. doi:10.1073/pnas.96.6.2639. PMC 15821. PMID 10077563. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15821. 
• Dowell P, Ishmael JE, Avram D, et al. (1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein.". J. Biol. Chem. 274 (22): 15901–7. doi:10.1074/jbc.274.22.15901. PMID 10336495. 
• Boutell JM, Thomas P, Neal JW, et al. (2000). "Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin.". Hum. Mol. Genet. 8 (9): 1647–55. doi:10.1093/hmg/8.9.1647. PMID 10441327. 
• Nagaya T, Chen KS, Fujieda M, et al. (1999). "Localization of the human nuclear receptor corepressor (hN-CoR) gene between the CMT1A and the SMS critical regions of chromosome 17p11.2.". Genomics 59 (3): 339–41. doi:10.1006/geno.1998.5694. PMID 10444336. 
• Kikuno R, Nagase T, Ishikawa K, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.". DNA Res. 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID 10470851. 
• Hu X, Lazar MA (1999). "The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors.". Nature 402 (6757): 93–6. doi:10.1038/47069. PMID 10573424. 
• Huang EY, Zhang J, Miska EA, et al. (2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway.". Genes Dev. 14 (1): 45–54. PMC 316335. PMID 10640275. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316335. 
• Morohoshi F, Mitani S, Mitsuhashi N, et al. (2000). "Structure and expression pattern of a human MTG8/ETO family gene, MTGR1.". Gene 241 (2): 287–95. doi:10.1016/S0378-1119(99)00481-3. PMID 10675041. 
• Masselink H, Bernards R (2000). "The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR.". Oncogene 19 (12): 1538–46. doi:10.1038/sj.onc.1203421. PMID 10734313. 

External links

• MeSH nuclear receptor corepressor 1
• NURSA C97