Nuclear receptor subfamily 1 group D member 2

Details

Name

Nuclear receptor subfamily 1 group D member 2

Synonyms

• EAR-1R
• Orphan nuclear hormone receptor BD73
• Rev-erb alpha-related receptor
• Rev-erb-beta
• RVR
• V-erbA-related protein 1-related

Gene Name

NR1D2

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051608|Nuclear receptor subfamily 1 group D member 2
MEVNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNSDTNGNPKNGDL
ANIEGILKNDRIDCSMKTSKSSAPGMTKSHSGVTKFSGMVLLCKVCGDVASGFHYGVHAC
EGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRDAVRFGRIP
KREKQRMLIEMQSAMKTMMNSQFSGHLQNDTLVEHHEQTALPAQEQLRPKPQLEQENIKS
SSPPSSDFAKEEVIGMVTRAHKDTFMYNQEQQENSAESMQPQRGERIPKNMEQYNLNHDH
CGNGLSSHFPCSESQQHLNGQFKGRNIMHYPNGHAICIANGHCMNFSNAYTQRVCDRVPI
DGFSQNENKNSYLCNTGGRMHLVCPLSKSPYVDPHKSGHEIWEEFSMSFTPAVKEVVEFA
KRIPGFRDLSQHDQVNLLKAGTFEVLMVRFASLFDAKERTVTFLSGKKYSVDDLHSMGAG
DLLNSMFEFSEKLNALQLSDEEMSLFTAVVLVSADRSGIENVNSVEALQETLIRALRTLI
MKNHPNEASIFTKLLLKLPDLRSLNNMHSEELLAFKVHP

Number of residues

579

Molecular Weight

64624.66

Theoretical pI

Not Available

GO Classification

Functions

core promoter sequence-specific DNA binding / nuclear receptor activity / RNA polymerase II distal enhancer sequence-specific DNA binding / RNA polymerase II transcription factor activity, sequence-specific DNA binding / steroid hormone receptor activity / transcriptional repressor activity, RNA polymerase II distal enhancer sequence-specific binding / zinc ion binding

Processes

lipid homeostasis / negative regulation of transcription, DNA-templated / positive regulation of transcription, DNA-templated / regulation of circadian rhythm / regulation of energy homeostasis / regulation of inflammatory response / regulation of lipid metabolic process / regulation of skeletal muscle cell differentiation / regulation of transcription, DNA-templated / rhythmic process / transcription initiation from RNA polymerase II promoter

Components

nucleoplasm / nucleus

General Function

Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle.

Specific Function

Core promoter sequence-specific dna binding

Pfam Domain Function

• Hormone_recep (PF00104)
• zf-C4 (PF00105)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0051609|Nuclear receptor subfamily 1 group D member 2 (NR1D2)
ATGGAGGTGAATGCAGGAGGTGTGATTGCCTATATCAGTTCTTCCAGCTCAGCCTCAAGC
CCTGCCTCTTGTCACAGTGAGGGTTCTGAGAATAGTTTCCAGTCCTCCTCCTCTTCTGTT
CCATCTTCTCCAAATAGCTCTAATTCTGATACCAATGGTAATCCCAAGAATGGTGATCTC
GCCAATATTGAAGGCATCTTGAAGAATGATCGAATAGATTGTTCTATGAAAACAAGCAAA
TCGAGTGCACCTGGGATGACAAAAAGTCATAGTGGTGTGACAAAATTTAGTGGCATGGTT
CTACTGTGTAAAGTCTGTGGGGATGTGGCGTCAGGATTCCACTATGGAGTTCATGCTTGC
GAAGGCTGTAAGGGTTTCTTTCGGAGAAGTATTCAACAAAACATCCAGTACAAGAAGTGC
CTGAAGAATGAAAACTGTTCTATAATGAGAATGAATAGGAACAGATGTCAGCAATGTCGC
TTCAAAAAGTGTCTGTCTGTTGGAATGTCAAGAGATGCTGTTCGGTTTGGTCGTATTCCT
AAGCGTGAAAAACAGAGGATGCTAATTGAAATGCAAAGTGCAATGAAGACCATGATGAAC
AGCCAGTTCAGTGGTCACTTGCAAAATGACACATTAGTAGAACATCATGAACAGACAGCC
TTGCCAGCCCAGGAACAGCTGCGACCCAAGCCCCAACTGGAGCAAGAAAACATCAAAAGC
TCTTCTCCTCCATCTTCTGATTTTGCAAAGGAAGAAGTGATTGGCATGGTGACCAGAGCT
CACAAGGATACCTTTATGTATAATCAAGAGCAGCAAGAAAACTCAGCTGAGAGCATGCAG
CCCCAGAGAGGAGAACGGATTCCCAAGAACATGGAGCAATATAATTTAAATCATGATCAT
TGCGGCAATGGGCTTAGCAGCCATTTTCCCTGTAGTGAGAGCCAGCAGCATCTCAATGGA
CAGTTCAAAGGGAGGAATATAATGCATTACCCAAATGGTCATGCCATTTGTATTGCAAAT
GGACATTGTATGAACTTCTCCAATGCTTATACTCAAAGAGTATGTGATAGAGTTCCGATA
GATGGATTTTCTCAGAATGAGAACAAGAATAGTTACCTGTGCAACACTGGAGGAAGAATG
CATCTGGTTTGTCCAATGAGTAAGTCTCCATATGTGGATCCTCATAAATCAGGACATGAA
ATCTGGGAAGAATTTTCGATGAGCTTCACTCCAGCAGTGAAAGAAGTGGTGGAATTTGCA
AAGCGTATTCCTGGGTTCAGAGATCTCTCTCAGCATGACCAGGTCAACCTTTTAAAGGCT
GGGACTTTTGAGGTTTTAATGGTACGGTTCGCATCATTATTTGATGCAAAGGAACGTACT
GTCACCTTTTTAAGTGGAAAGAAATATAGTGTGGATGATTTACACTCAATGGGAGCAGGG
GATCTGCTAAACTCTATGTTTGAATTTAGTGAGAAGCTAAATGCCCTCCAACTTAGTGAT
GAAGAGATGAGTTTGTTTACAGCTGTTGTCCTGGTATCTGCAGATCGATCTGGAATAGAA
AACGTCAACTCTGTGGAGGCTTTGCAGGAAACTCTCATTCGTGCACTAAGGACCTTAATA
ATGAAAAACCATCCAAATGAGGCCTCTATTTTTACAAAACTGCTTCTAAAGTTGCCAGAT
CTTCGATCTTTAAACAACATGCACTCTGAGGAGCTCTTGGCCTTTAAAGTTCACCCTTAA

Chromosome Location

3

Locus

3p24.2

External Identifiers

Resource	Link
UniProtKB ID	Q14995
UniProtKB Entry Name	NR1D2_HUMAN
HGNC ID	HGNC:7963

General References

1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
2. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. [Article]
3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
4. Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD: A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb. Mol Endocrinol. 1994 Aug;8(8):996-1005. doi: 10.1210/mend.8.8.7997240. [Article]
5. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [Article]
6. Wang J, Li Y, Zhang M, Liu Z, Wu C, Yuan H, Li YY, Zhao X, Lu H: A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor Rev-erbbeta and removes Rev-erbbeta-induced inhibition of apoCIII transcription. FEBS J. 2007 Oct;274(20):5370-81. doi: 10.1111/j.1742-4658.2007.06062.x. Epub 2007 Sep 24. [Article]
7. Wang J, Liu N, Liu Z, Li Y, Song C, Yuan H, Li YY, Zhao X, Lu H: The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to regulate apolipoprotein CIII promoter. Biochim Biophys Acta. 2008 Feb;1783(2):224-36. Epub 2007 Oct 4. [Article]
8. Gupta N, Ragsdale SW: Thiol-disulfide redox dependence of heme binding and heme ligand switching in nuclear hormone receptor rev-erb{beta}. J Biol Chem. 2011 Feb 11;286(6):4392-403. doi: 10.1074/jbc.M110.193466. Epub 2010 Dec 1. [Article]
9. Stratmann M, Schibler U: REV-ERBs: more than the sum of the individual parts. Cell Metab. 2012 Jun 6;15(6):791-3. doi: 10.1016/j.cmet.2012.05.006. [Article]
10. Ripperger JA, Albrecht U: REV-ERB-erating nuclear receptor functions in circadian metabolism and physiology. Cell Res. 2012 Sep;22(9):1319-21. doi: 10.1038/cr.2012.81. Epub 2012 May 22. [Article]
11. Woo EJ, Jeong DG, Lim MY, Jun Kim S, Kim KJ, Yoon SM, Park BC, Ryu SE: Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta. J Mol Biol. 2007 Oct 26;373(3):735-44. doi: 10.1016/j.jmb.2007.08.037. Epub 2007 Aug 22. [Article]
12. Pardee KI, Xu X, Reinking J, Schuetz A, Dong A, Liu S, Zhang R, Tiefenbach J, Lajoie G, Plotnikov AN, Botchkarev A, Krause HM, Edwards A: The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta. PLoS Biol. 2009 Feb 24;7(2):e43. doi: 10.1371/journal.pbio.1000043. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB14013	SR-9009	experimental	unknown	agonist	Details
DB14014	SR-9011	experimental	unknown	agonist	Details