Nuclear receptor co-repressor 1

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.[5][6]

NCOR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EQR, 3H52, 3KMZ, 3N00, 4MDD, 4WVD
Identifiers
Aliases	NCOR1, N-CoR, N-CoR1, PPP1R109, TRAC1, hN-CoR, nuclear receptor corepressor 1
External IDs	OMIM: 600849 MGI: 1349717 HomoloGene: 38166 GeneCards: NCOR1
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p12-p11.2 Start 16,029,157 bp[1] End 16,218,185 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B2 Start 62,316,426 bp[2] End 62,458,541 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001106 transcription corepressor activity • histone deacetylase binding • nuclear hormone receptor binding • thyroid hormone receptor binding • RNA polymerase II activating transcription factor binding • GO:0001948 protein binding • ligand-dependent nuclear receptor binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • chromatin binding • sequence-specific DNA binding Cellular component • histone deacetylase complex • membrane • transcriptional repressor complex • Sin3 complex • spindle microtubule • nuclear chromatin • cell nucleus • nucleoplasm • cytosol • mitotic spindle Biological process • regulation of transcription, DNA-templated • negative regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • negative regulation of production of miRNAs involved in gene silencing by miRNA • spindle assembly • negative regulation of JNK cascade • regulation of fatty acid transport • circadian rhythm • transcription, DNA-templated • covalent chromatin modification • regulation of lipid metabolic process • chromatin organization • negative regulation of transcription, DNA-templated • negative regulation of androgen receptor signaling pathway • locomotor rhythm • rhythmic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9611	20185
Ensembl	ENSG00000141027	ENSMUSG00000018501
UniProt	O75376	Q60974
RefSeq (mRNA)	NM_001190438 NM_001190440 NM_006311	NM_001252313 NM_011308 NM_177229
RefSeq (protein)	NP_001177367 NP_001177369 NP_006302	n/a
Location (UCSC)	Chr 17: 16.03 – 16.22 Mb	Chr 11: 62.32 – 62.46 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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 gene expression.[5][7]

Loss of function of this protein significantly increases the strength and power of mouse muscles.[8]

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 2.[9]

Interactions

Nuclear receptor co-repressor 1 has been shown to interact with:

• Androgen receptor,[10][11][12][13]
• CHD1,[14]
• Calcitriol receptor[15][16]
• GPS2,[17][18][19]
• Glucocorticoid receptor,[20][21]
• HDAC3,[17][18][19][22][23][24][25]
• HDAC4,[24][26]
• HDAC7A,[22]
• HDAC9,[27]
• HEY2,[28]
• Histone deacetylase 5,[17][26]
• MAP3K7IP2,[29]
• MECP2,[30]
• Peroxisome proliferator-activated receptor alpha,[31]
• Peroxisome proliferator-activated receptor gamma
• Promyelocytic leukemia protein,[32]
• RUNX1T1,[33][34]
• Retinoic acid receptor alpha,[31][35]
• Retinoic acid receptor gamma,[31]
• SAP30,[25][36]
• TBL1XR1,[17][18][19]
• TBL1X,[17][19][23][37] and
• ZBTB33.[18]

References

1. GRCh38: Ensembl release 89: ENSG00000141027 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000018501 - 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. 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.
6. 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. Bibcode:1998PNAS...9510860W. doi:10.1073/pnas.95.18.10860. PMC 27986. PMID 9724795.
7. 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. Bibcode:1998PNAS...9510860W. doi:10.1073/pnas.95.18.10860. PMC 27986. PMID 9724795.
8. Yamamoto H, Williams EG, Mouchiroud L, Cantó C, Fan W, Downes M, Héligon C, Barish GD, Desvergne B, Evans RM, Schoonjans K, Auwerx J (2011). "NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function". Cell. 147 (4): 827–839. doi:10.1016/j.cell.2011.10.017. PMC 3225739. PMID 22078881.
9. UniProt Nuclear receptor corepressors family Page accessed June 26, 2016
10. Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP (October 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Mol. Endocrinol. 18 (10): 2388–401. doi:10.1210/me.2003-0436. PMID 15256534.
11. Song LN, Coghlan M, Gelmann EP (January 2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. 18 (1): 70–85. doi:10.1210/me.2003-0189. PMID 14593076.
12. Cheng S, Brzostek S, Lee SR, Hollenberg AN, Balk SP (July 2002). "Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor". Mol. Endocrinol. 16 (7): 1492–501. doi:10.1210/mend.16.7.0870. PMID 12089345.
13. Hodgson MC, Astapova I, Cheng S, Lee LJ, Verhoeven MC, Choi E, Balk SP, Hollenberg AN (February 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. 280 (8): 6511–9. doi:10.1074/jbc.M408972200. PMID 15598662.
14. Tai HH, Geisterfer M, Bell JC, Moniwa M, Davie JR, Boucher L, McBurney MW (August 2003). "CHD1 associates with NCoR and histone deacetylase as well as with RNA splicing proteins". Biochem. Biophys. Res. Commun. 308 (1): 170–6. doi:10.1016/s0006-291x(03)01354-8. PMID 12890497.
15. 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 Res. 62 (23): 7050–8. PMID 12460926.
16. Tagami T, Lutz WH, Kumar R, Jameson JL (December 1998). "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochem. Biophys. Res. Commun. 253 (2): 358–63. doi:10.1006/bbrc.1998.9799. PMID 9878542.
17. Zhang J, Kalkum M, Chait BT, Roeder RG (March 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Mol. Cell. 9 (3): 611–23. doi:10.1016/s1097-2765(02)00468-9. PMID 11931768.
18. 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". Mol. Cell. 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
19. Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (March 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". EMBO J. 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926.
20. Stevens A, Garside H, Berry A, Waters C, White A, Ray D (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. 17 (5): 845–59. doi:10.1210/me.2002-0320. PMID 12569182.
21. Schulz M, Eggert M, Baniahmad A, Dostert A, Heinzel T, Renkawitz R (July 2002). "RU486-induced glucocorticoid receptor agonism is controlled by the receptor N terminus and by corepressor binding". J. Biol. Chem. 277 (29): 26238–43. doi:10.1074/jbc.M203268200. PMID 12011091.
22. Fischle W, Dequiedt F, Fillion M, Hendzel MJ, Voelter W, Verdin E (September 2001). "Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo". J. Biol. Chem. 276 (38): 35826–35. doi:10.1074/jbc.M104935200. PMID 11466315.
23. Li J, Wang J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J (August 2000). "Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3". EMBO J. 19 (16): 4342–50. doi:10.1093/emboj/19.16.4342. PMC 302030. PMID 10944117.
24. 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". Mol. Cell. 9 (1): 45–57. doi:10.1016/s1097-2765(01)00429-4. hdl:11858/00-001M-0000-002C-9FF9-9. PMID 11804585.
25. Underhill C, Qutob MS, Yee SP, Torchia J (December 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. 275 (51): 40463–70. doi:10.1074/jbc.M007864200. PMID 11013263.
26. 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 Dev. 14 (1): 45–54. PMC 316335. PMID 10640275.
27. Petrie K, Guidez F, Howell L, Healy L, Waxman S, Greaves M, Zelent A (May 2003). "The histone deacetylase 9 gene encodes multiple protein isoforms". J. Biol. Chem. 278 (18): 16059–72. doi:10.1074/jbc.M212935200. PMID 12590135.
28. Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, Kedes L, Hamamori Y (September 2001). "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling". Mol. Cell. Biol. 21 (17): 6080–9. doi:10.1128/mcb.21.17.6080-6089.2001. PMC 87325. PMID 11486045.
29. Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG (July 2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell. 110 (1): 55–67. doi:10.1016/S0092-8674(02)00809-7. PMID 12150997.
30. Kokura K, Kaul SC, Wadhwa R, Nomura T, Khan MM, Shinagawa T, Yasukawa T, Colmenares C, Ishii S (September 2001). "The Ski protein family is required for MeCP2-mediated transcriptional repression". J. Biol. Chem. 276 (36): 34115–21. doi:10.1074/jbc.M105747200. PMID 11441023.
31. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 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.
32. 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". Mol. Cell. 7 (6): 1233–43. doi:10.1016/s1097-2765(01)00257-x. PMID 11430826.
33. Amann JM, Nip J, Strom DK, Lutterbach B, Harada H, Lenny N, Downing JR, Meyers S, Hiebert SW (October 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. 21 (19): 6470–83. doi:10.1128/mcb.21.19.6470-6483.2001. PMC 99794. PMID 11533236.
34. Zhang J, Hug BA, Huang EY, Chen CW, Gelmetti V, Maccarana M, Minucci S, Pelicci PG, Lazar MA (January 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. 21 (1): 156–63. doi:10.1128/MCB.21.1.156-163.2001. PMC 88789. PMID 11113190.
35. Guidez F, Ivins S, Zhu J, Söderström M, Waxman S, Zelent A (April 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. doi:10.1182/blood.V91.8.2634.2634_2634_2642. PMID 9531570.
36. 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". Mol. Cell. 2 (1): 33–42. doi:10.1016/s1097-2765(00)80111-2. PMID 9702189.
37. 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 Dev. 14 (9): 1048–57. doi:10.1101/gad.14.9.1048 (inactive 2020-05-21). PMC 316569. PMID 10809664.

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.
• 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. doi:10.1128/mcb.17.5.2642. PMC 232114. PMID 9111334.
• Zamir I, Dawson J, Lavinsky RM, Glass CK, Rosenfeld MG, Lazar MA (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.
• 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, Söderström M, Waxman S, Zelent A (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. doi:10.1182/blood.V91.8.2634.2634_2634_2642. PMID 9531570.
• Kao HY, Ordentlich P, Koyano-Nakagawa N, Tang Z, Downes M, Kintner CR, Evans RM, Kadesch T (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.
• 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 (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, 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. U.S.A. 95 (18): 10860–5. Bibcode:1998PNAS...9510860W. doi:10.1073/pnas.95.18.10860. PMC 27986. PMID 9724795.
• Ordentlich P, Downes M, Xie W, Genin A, Spinner NB, Evans RM (1999). "Unique forms of human and mouse nuclear receptor corepressor SMRT". Proc. Natl. Acad. Sci. U.S.A. 96 (6): 2639–44. Bibcode:1999PNAS...96.2639O. doi:10.1073/pnas.96.6.2639. PMC 15821. PMID 10077563.
• Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (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, Weston VJ, Duce J, Harper PS, Jones 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, Ohmori S, Richer JK, Horwitz KB, Lupski JR, Seo H (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, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (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. Bibcode:1999Natur.402...93H. doi:10.1038/47069. PMID 10573424.
• Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (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.
• Morohoshi F, Mitani S, Mitsuhashi N, Kitabayashi I, Takahashi E, Suzuki M, Munakata N, Ohki M (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

• nuclear receptor corepressor 1 at the US National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C97
• Overview of all the structural information available in the PDB for UniProt: O75376 (Nuclear receptor corepressor 1) at the PDBe-KB.