Nuclear receptor subfamily 1 group D member 1

Details

Name
Nuclear receptor subfamily 1 group D member 1
Synonyms
  • EAR-1
  • EAR1
  • HREV
  • Rev-erbA-alpha
  • THRAL
  • V-erbA-related protein 1
Gene Name
NR1D1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051606|Nuclear receptor subfamily 1 group D member 1 MTTLDSNNNTGGVITYIGSSGSSPSRTSPESLYSDNSNGSFQSLTQGCPTYFPPSPTGSL TQDPARSFGSIPPSLSDDGSPSSSSSSSSSSSSFYNGSPPGSLQVAMEDSSRVSPSKSTS NITKLNGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKRCLKNENCSIVRI NRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLAEMQSAMNLANNQLSSQCPLETS PTQHPTPGPMGPSPPPAPVPSPLVGFSQFPQQLTPPRSPSPEPTVEDVISQVARAHREIF TYAHDKLGSSPGNFNANHASGSPPATTPHRWENQGCPPAPNDNNTLAAQRHNEALNGLRQ APSSYPPTWPPGPAHHSCHQSNSNGHRLCPTHVYAAPEGKAPANSPRQGNSKNVLLACPM NMYPHGRSGRTVQEIWEDFSMSFTPAVREVVEFAKHIPGFRDLSQHDQVTLLKAGTFEVL MVRFASLFNVKDQTVMFLSRTTYSLQELGAMGMGDLLSAMFDFSEKLNSLALTEEELGLF TAVVLVSADRSGMENSASVEQLQETLLRALRALVLKNRPLETSRFTKLLLKLPDLRTLNN MHSEKLLSFRVDAQ
Number of residues
614
分子量
66804.595
Theoretical pI
Not Available
GO Classification
Functions
core promoter sequence-specific DNA binding/heme binding/nuclear receptor activity/RNA polymerase II proximal promoter sequence-specific DNA binding/RNA polymerase II regulatory region sequence-specific DNA binding/RNA polymerase II transcription factor activity, sequence-specific DNA binding/steroid hormone receptor activity/transcription corepressor activity/transcription corepressor binding/transcription regulatory region DNA binding/transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding/zinc ion binding
Processes
cell differentiation/cellular response to lipopolysaccharide/circadian regulation of gene expression/circadian rhythm/circadian temperature homeostasis/glycogen biosynthetic process/negative regulation of receptor biosynthetic process/negative regulation of toll-like receptor 4 signaling pathway/negative regulation of transcription by RNA polymerase II/negative regulation of transcription, DNA-templated/positive regulation of bile acid biosynthetic process/positive regulation of transcription, DNA-templated/proteasomal protein catabolic process/regulation of cholesterol homeostasis/regulation of circadian rhythm/regulation of fat cell differentiation/regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter/regulation of insulin secretion involved in cellular response to glucose stimulus/regulation of lipid metabolic process/regulation of type B pancreatic cell proliferation/response to leptin/transcription initiation from RNA polymerase II promoter
Components
cytoplasm/dendrite/dendritic spine/nuclear body/nuclear chromatin/nucleoplasm/nucleus
General Function
坐标circad转录抑制因子ian 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 ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage 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 nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner.
Specific Function
Core promoter sequence-specific dna binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>拼箱| BSEQ0051607 |核受体亚科1组织p D member 1 (NR1D1) ATGACGACCCTGGACTCCAACAACAACACAGGTGGCGTCATCACCTACATTGGCTCCAGT GGCTCCTCCCCAAGCCGCACCAGCCCTGAATCCCTCTATAGTGACAACTCCAATGGCAGC TTCCAGTCCCTGACCCAAGGCTGTCCCACCTACTTCCCACCATCCCCCACTGGCTCCCTC ACCCAAGACCCGGCTCGCTCCTTTGGGAGCATTCCACCCAGCCTGAGTGATGACGGCTCC CCTTCTTCCTCATCTTCCTCGTCGTCATCCTCCTCCTCCTTCTATAATGGGAGCCCCCCT GGGAGTCTACAAGTGGCCATGGAGGACAGCAGCCGAGTGTCCCCCAGCAAGAGCACCAGC AACATCACCAAGCTGAATGGCATGGTGTTACTGTGTAAAGTGTGTGGGGACGTTGCCTCG GGCTTCCACTACGGTGTGCACGCCTGCGAGGGCTGCAAGGGCTTTTTCCGTCGGAGCATC CAGCAGAACATCCAGTACAAAAGGTGTCTGAAGAATGAGAATTGCTCCATCGTCCGCATC AATCGCAACCGCTGCCAGCAATGTCGCTTCAAGAAGTGTCTCTCTGTGGGCATGTCTCGA GACGCTGTGCGTTTTGGGCGCATCCCCAAACGAGAGAAGCAGCGGATGCTTGCTGAGATG CAGAGTGCCATGAACCTGGCCAACAACCAGTTGAGCAGCCAGTGCCCGCTGGAGACTTCA CCCACCCAGCACCCCACCCCAGGCCCCATGGGCCCCTCGCCACCCCCTGCTCCGGTCCCC TCACCCCTGGTGGGCTTCTCCCAGTTTCCACAACAGCTGACGCCTCCCAGATCCCCAAGC CCTGAGCCCACAGTGGAGGATGTGATATCCCAGGTGGCCCGGGCCCATCGAGAGATCTTC ACCTACGCCCATGACAAGCTGGGCAGCTCACCTGGCAACTTCAATGCCAACCATGCATCA GGTAGCCCTCCAGCCACCACCCCACATCGCTGGGAAAATCAGGGCTGCCCACCTGCCCCC AATGACAACAACACCTTGGCTGCCCAGCGTCATAACGAGGCCCTAAATGGTCTGCGCCAG GCTCCCTCCTCCTACCCTCCCACCTGGCCTCCTGGCCCTGCACACCACAGCTGCCACCAG TCCAACAGCAACGGGCACCGTCTATGCCCCACCCACGTGTATGCAGCCCCAGAAGGCAAG GCACCTGCCAACAGTCCCCGGCAGGGCAACTCAAAGAATGTTCTGCTGGCATGTCCTATG AACATGTACCCGCATGGACGCAGTGGGCGAACGGTGCAGGAGATCTGGGAGGATTTCTCC ATGAGCTTCACGCCCGCTGTGCGGGAGGTGGTAGAGTTTGCCAAACACATCCCGGGCTTC CGTGACCTTTCTCAGCATGACCAAGTCACCCTGCTTAAGGCTGGCACCTTTGAGGTGCTG ATGGTGCGCTTTGCTTCGTTGTTCAACGTGAAGGACCAGACAGTGATGTTCCTAAGCCGC ACCACCTACAGCCTGCAGGAGCTTGGTGCCATGGGCATGGGAGACCTGCTCAGTGCCATG TTCGACTTCAGCGAGAAGCTCAACTCCCTGGCGCTTACCGAGGAGGAGCTGGGCCTCTTC ACCGCGGTGGTGCTTGTCTCTGCAGACCGCTCGGGCATGGAGAATTCCGCTTCGGTGGAG CAGCTCCAGGAGACGCTGCTGCGGGCTCTTCGGGCTCTGGTGCTGAAGAACCGGCCCTTG GAGACTTCCCGCTTCACCAAGCTGCTGCTCAAGCTGCCGGACCTGCGGACCCTGAACAAC ATGCATTCCGAGAAGCTGCTGTCCTTCCGGGTGGACGCCCAGTGA
Chromosome Location
17
Locus
17q21.1
External Identifiers
Resource Link
UniProtKB ID P20393
UniProtKB Entry Name NR1D1_HUMAN
HGNC ID HGNC:7962
General References
  1. Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T: Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell. 1989 Apr 7;57(1):31-9. [Article]
  2. Lazar MA, Jones KE, Chin WW: Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone. DNA Cell Biol. 1990 Mar;9(2):77-83. doi: 10.1089/dna.1990.9.77. [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. Laudet V, Begue A, Henry-Duthoit C, Joubel A, Martin P, Stehelin D, Saule S: Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene. Nucleic Acids Res. 1991 Mar 11;19(5):1105-12. [Article]
  5. Coste H, Rodriguez JC: Orphan nuclear hormone receptor Rev-erbalpha regulates the human apolipoprotein CIII promoter. J Biol Chem. 2002 Jul 26;277(30):27120-9. doi: 10.1074/jbc.M203421200. Epub 2002 May 20. [Article]
  6. Yin L, Lazar MA: The orphan nuclear receptor Rev-erbalpha recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 gene. Mol Endocrinol. 2005 Jun;19(6):1452-9. doi: 10.1210/me.2005-0057. Epub 2005 Mar 10. [Article]
  7. Wang J, Yin L, Lazar MA: The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1. J Biol Chem. 2006 Nov 10;281(45):33842-8. doi: 10.1074/jbc.M607873200. Epub 2006 Sep 11. [Article]
  8. Yin L, Wang J, Klein PS, Lazar MA: Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock. Science. 2006 Feb 17;311(5763):1002-5. [Article]
  9. 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]
  10. Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA: Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science. 2007 Dec 14;318(5857):1786-9. doi: 10.1126/science.1150179. Epub 2007 Nov 15. [Article]
  11. Wu N, Yin L, Hanniman EA, Joshi S, Lazar MA: Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalpha. Genes Dev. 2009 Sep 15;23(18):2201-9. doi: 10.1101/gad.1825809. Epub 2009 Aug 26. [Article]
  12. Yin L, Wu N, Lazar MA: Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl Recept Signal. 2010 Apr 16;8:e001. doi: 10.1621/nrs.08001. [Article]
  13. Valnegri P, Khelfaoui M, Dorseuil O, Bassani S, Lagneaux C, Gianfelice A, Benfante R, Chelly J, Billuart P, Sala C, Passafaro M: A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbalpha. Nat Neurosci. 2011 Aug 28;14(10):1293-301. doi: 10.1038/nn.2911. [Article]
  14. Lamia KA, Papp SJ, Yu RT, Barish GD, Uhlenhaut NH, Jonker JW, Downes M, Evans RM: Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature. 2011 Dec 14;480(7378):552-6. doi: 10.1038/nature10700. [Article]
  15. Crumbley C, Burris TP: Direct regulation of CLOCK expression by REV-ERB. PLoS One. 2011 Mar 29;6(3):e17290. doi: 10.1371/journal.pone.0017290. [Article]
  16. 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]
  17. 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]
  18. Gibbs JE, Blaikley J, Beesley S, Matthews L, Simpson KD, Boyce SH, Farrow SN, Else KJ, Singh D, Ray DW, Loudon AS: The nuclear receptor REV-ERBalpha mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):582-7. doi: 10.1073/pnas.1106750109. Epub 2011 Dec 19. [Article]
  19. Chini CC, Escande C, Nin V, Chini EN: DBC1(删除d in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbalpha. Biochem J. 2013 May 1;451(3):453-61. doi: 10.1042/BJ20121085. [Article]
  20. Nin V, Chini CC, Escande C, Capellini V, Chini EN: Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis. J Biol Chem. 2014 Feb 28;289(9):5518-27. doi: 10.1074/jbc.M113.512913. Epub 2014 Jan 10. [Article]
  21. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  22. 赵Q, Khorasanizadeh S, Miyoshi Y, Lazar MA, Rastinejad F: Structural elements of an orphan nuclear receptor-DNA complex. Mol Cell. 1998 May;1(6):849-61. [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