Rev-ErbA alpha

Nuclear receptor subfamily 1, group D, member 1
The DNA binding domain of NR1D1 bound to double stranded DNA.[1]
Available structures PDB 1a6y, 1ga5, 1hlz, 3N00
Identifiers
Symbols	NR1D1; THRA1; EAR1; THRAL; ear-1; hRev
External IDs	OMIM: 602408 MGI: 2444210 HomoloGene: 23324 IUPHAR: NR1D1 GeneCards: NR1D1 Gene
Gene Ontology Molecular function • transcription factor activity • steroid hormone receptor activity • transcription corepressor activity • zinc ion binding • sequence-specific DNA binding • metal ion binding Cellular component • nucleus Biological process • transcription • regulation of transcription, DNA-dependent • circadian rhythm Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9572	217166
Ensembl	ENSG00000126368	ENSMUSG00000020889
UniProt	P20393	Q3UV55
RefSeq (mRNA)	NM_021724	NM_145434
RefSeq (protein)	NP_068370	NP_663409
Location (UCSC)	Chr 17: 35.5 – 35.51 Mb	Chr 11: 98.58 – 98.59 Mb
PubMed search	[1]	[2]
This box: view · protein that in humans is encoded by the NR1D1 gene.[2] Rev-erbα is member of the Rev-ErbA family of nuclear receptors and is a transcriptional repressor.[3] In mammals, Rev-erbα is highly expressed in the liver, skeletal muscle, adipose tissue, and the brain, participating in the development and circadian regulation of these tissues.[4][5] Gene and protein structure Rev-erbα is transcribed from the opposite strand of the thyroid receptor α (c-erbAα) gene on chromosome 17, with a 269-nucleotide overlap between the two transcripts.[3] The other mammalian isoform of the receptor, Rev-erbβ is encoded by another gene on chromosome 3. In addition, there is one non-mammalian homolog, the ecdysone-regulated gene E75, which is present in Drosophila and C. elegans. The Rev-erbα gene itself has multiple transcripts. Two promoters govern the expression of the Rev-erbα gene in human and rat, generating two mRNA isoforms. The full-length isoform encodes a 614-amino acid protein, while a second isoform is generated from an internal promoter and produces a protein that is shorter by 106 amino acids. Both Rev-erbα mRNA isoforms contain E-boxes as well as Rev-erbα response elements, which means that they can be regulated in a circadian manner by the BMAL and Rev-erba proteins. In fact, both transcripts exhibit rhythmic expression in serum-synchronized fibroblasts. The Rev-erbα protein is structurally unique from other nuclear receptors, in that it lacks helix 12 (H12) in its ligand-binding domain, which is usually responsible for forming the ligand binding pocket in other nuclear receptors. In place of the missing H12, Rev-erbα displays a hydrophobic interface that binds the corepressor N-CoR, making it a potent transcriptional repressor.[6] Interestingly, all members of the Rev-erb family bind heme, which may act as a ligand to regulate their transcriptional activity.[7] Physiologic function Rev-erbα regulates gene transcription by directly binding to target response elements (RevREs), comprises an A/T-rich flank followed by AGGTCA. Rev-erbα mediates repression by recruiting the corepressor N-CoR, which then activates the histone deacetylase (HDAC) 3. A number of target genes has been identified for Rev-erbα, including the lipoproteins ApoA1 and ApoCIII, hydratase dehydrogenase, the circadian factor BMAL, and the anti-fibrinolytic factor PAI-1.[8] Many of these genes are coordinately regulated by Rev-erbα and the RAR-related orphan receptor RORα, which share the same response elements but exert opposite effects on gene transcription. Crosstalk between Rev-erbα and RORα likely acts to fine-tune of their target physiologic networks, such as circadian rhythms, metabolic homeostasis, and inflammation.[9] Rev-erbα mRNA is induced during adipogenesis and is highly expressed in adipose tissue.[10] One study reported that overexpression of Rev-erbα may enhance adipogenesis in cultured mouse adipocytes, but the mechanism of this effect remains to be elucidated.[11] Rev-erbα expression is also regulated at the post-translational level: it is phosphorylated on the amino terminus by glycogen synthase kinase (GSK 3β), which contributes to its protein stability. It has been shown that lithium, which inhibits GSK3β, can de-stabilize Rev-erbα protein and affect its function in the circadian clock.[12] This may partly explain lithium’s therapeutic effect on circadian diseases such as bipolar disorder. References ^ PDB 1a6yZhao Q, Khorasanizadeh S, Miyoshi Y, Lazar MA, Rastinejad F (May 1998). "Structural elements of an orphan nuclear receptor-DNA complex". Mol. Cell 1 (6): 849–61. doi:10.1016/S1097-2765(00)80084-2. PMID 9660968.  ^ Lazar MA, Jones KE, Chin WW (March 1990). "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. 9 (2): 77–83. doi:10.1089/dna.1990.9.77. PMID 1971514.  ^ a b Lazar MA, Hodin RA, Cardona G, Chin WW (1990). "Gene expression from the c-erbA α/Rev-ErbA α genomic locus. Potential regulation of alternative splicing by opposite strand transcription". J. Biol. Chem. 265 (22): 12859–63. PMID 2165488. http://www.jbc.org/cgi/content/abstract/265/22/12859.  ^ Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U (2002). "The orphan nuclear receptor REV-ERBα controls circadian transcription within the positive limb of the mammalian circadian oscillator". Cell 110 (2): 251–60. doi:10.1016/S0092-8674(02)00825-5. PMID 12150932.  ^ Triqueneaux G, Thenot S, Kakizawa T, Antoch MP, Safi R, Takahashi JS, Delaunay F, Laudet V (2004). "The orphan receptor Rev-erbα gene is a target of the circadian clock pacemaker". J. Mol. Endocrinol. 33 (3): 585–608. doi:10.1677/jme.1.01554. PMID 15591021.  ^ Woo EJ, Jeong DG, Lim MY, Jun Kim S, Kim KJ, Yoon SM, Park BC, Eon Ryu S (2007). "Structural Insight into the Constitutive Repression Function of the Nuclear Receptor Rev-erbβ". J. Mol. Biol. 373 (3): 735–44. doi:10.1016/j.jmb.2007.08.037. PMID 17870090.  ^ Raghuram S, Stayrook KR, Huang P, Rogers PM, Nosie AK, McClure DB, Burris LL, Khorasanizadeh S, Burris TP, Rastinejad F (December 2007). "Identification of heme as the ligand for the orphan nuclear receptors REV-ERBα and REV-ERBβ". Nat. Struct. Mol. Biol. 14 (12): 1207–13. doi:10.1038/nsmb1344. PMC 2743565. PMID 18037887. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2743565.  ^ Wang J, Yin L, Lazar MA (2006). "The orphan nuclear receptor Rev-erb α regulates circadian expression of plasminogen activator inhibitor type 1". J. Biol. Chem. 281 (45): 33842–8. doi:10.1074/jbc.M607873200. PMID 16968709.  ^ Forman BM, Chen J, Blumberg B, Kliewer SA, Henshaw R, Ong ES, Evans RM (1994). "Cross-talk among ROR α 1 and the Rev-erb family of orphan nuclear receptors". Mol. Endocrinol. 8 (9): 1253–61. doi:10.1210/me.8.9.1253. PMID 7838158.  ^ Fontaine C, Dubois G, Duguay Y, Helledie T, Vu-Dac N, Gervois P, Soncin F, Mandrup S, Fruchart JC, Fruchart-Najib J, Staels B (2003). "The orphan nuclear receptor Rev-Erbα is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation". J. Biol. Chem. 278 (39): 37672–80. doi:10.1074/jbc.M304664200. PMID 12821652.  ^ Chawla A, Lazar MA (1993). "Induction of Rev-ErbA α, an orphan receptor encoded on the opposite strand of the α-thyroid hormone receptor gene, during adipocyte differentiation". J. Biol. Chem. 268 (22): 16265–9. PMID 8344913. http://www.jbc.org/cgi/content/abstract/268/22/16265.  ^ Yin L, Wang J, Klein PS, Lazar MA (2006). "Nuclear receptor Rev-erbα is a critical lithium-sensitive component of the circadian clock". Science 311 (5763): 1002–5. doi:10.1126/science.1121613. PMID 16484495.  Further reading Laudet V, Begue A, Henry-Duthoit C et al. (1991). "Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene". Nucleic Acids Res. 19 (5): 1105–12. doi:10.1093/nar/19.5.1105. PMC 333788. PMID 1850510. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=333788.  Miyajima N, Horiuchi R, Shibuya Y et al. (1989). "Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus". Cell 57 (1): 31–9. doi:10.1016/0092-8674(89)90169-4. PMID 2539258.  Adelmant G, Bègue A, Stéhelin D, Laudet V (1996). "A functional Rev-erb alpha responsive element located in the human Rev-erb alpha promoter mediates a repressing activity". Proc. Natl. Acad. Sci. U.S.A. 93 (8): 3553–8. doi:10.1073/pnas.93.8.3553. PMC 39648. PMID 8622974. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=39648.  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.  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.  Zhao Q, Khorasanizadeh S, Miyoshi Y et al. (1998). "Structural elements of an orphan nuclear receptor-DNA complex". Mol. Cell 1 (6): 849–61. doi:10.1016/S1097-2765(00)80084-2. PMID 9660968.  Sierk ML, Zhao Q, Rastinejad F (2001). "DNA deformability as a recognition feature in the reverb response element". Biochemistry 40 (43): 12833–43. doi:10.1021/bi011086r. PMID 11669620.  Coste H, Rodríguez JC (2002). "Orphan nuclear hormone receptor Rev-erbalpha regulates the human apolipoprotein CIII promoter". J. Biol. Chem. 277 (30): 27120–9. doi:10.1074/jbc.M203421200. PMID 12021280.  Delerive P, Chin WW, Suen CS (2002). "Identification of Reverb(alpha) as a novel ROR(alpha) target gene". J. Biol. Chem. 277 (38): 35013–8. doi:10.1074/jbc.M202979200. PMID 12114512.  Raspè E, Mautino G, Duval C et al. (2003). "Transcriptional regulation of human Rev-erbalpha gene expression by the orphan nuclear receptor retinoic acid-related orphan receptor alpha". J. Biol. Chem. 277 (51): 49275–81. doi:10.1074/jbc.M206215200. PMID 12377782.  Raspé E, Duez H, Mansén A et al. (2003). "Identification of Rev-erbalpha as a physiological repressor of apoC-III gene transcription". J. Lipid Res. 43 (12): 2172–9. doi:10.1194/jlr.M200386-JLR200. PMID 12454280.  Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.  Chopin-Delannoy S, Thénot S, Delaunay F et al. (2004). "A specific and unusual nuclear localization signal in the DNA binding domain of the Rev-erb orphan receptors". J. Mol. Endocrinol. 30 (2): 197–211. doi:10.1677/jme.0.0300197. PMID 12683943.  Fontaine C, Dubois G, Duguay Y et al. (2003). "The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation". J. Biol. Chem. 278 (39): 37672–80. doi:10.1074/jbc.M304664200. PMID 12821652.  Johnson JM, Castle J, Garrett-Engele P et al. (2004). "Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays". Science 302 (5653): 2141–4. doi:10.1126/science.1090100. PMID 14684825.  Migita H, Morser J, Kawai K (2004). "Rev-erbalpha upregulates NF-kappaB-responsive genes in vascular smooth muscle cells". FEBS Lett. 561 (1–3): 69–74. doi:10.1016/S0014-5793(04)00118-8. PMID 15013753.  Cheng H, Khanna H, Oh EC et al. (2005). "Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors". Hum. Mol. Genet. 13 (15): 1563–75. doi:10.1093/hmg/ddh173. PMID 15190009.  Beausoleil SA, Jedrychowski M, Schwartz D et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514446.  Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.  External links MeSH NR1D1+protein,+human Wikimedia Foundation. 2010. Игры ⚽ Поможем сделать НИР TRPA1 FBXL3 Look at other dictionaries: Rev-ErbA — The Rev ErbA proteins are members of the nuclear receptor family of intracellular transcription factors. There are two forms of the receptor, alpha and beta, each encoded by a separate gene (gene|NR1D1 and gene|NR1D2 respectively).cite journal |… …   Wikipedia Rev-ErbA beta — Nuclear receptor subfamily 1, group D, member 2 Structure of the ligand binding domain (LBD) of the Rev erb? receptor based on PDB 2v0v. Depicted here is a dimer of comprising two LBD protein molecules …   Wikipedia Thyroid hormone receptor alpha — Thyroid hormone receptor, alpha PDB rendering based on 1nav …   Wikipedia Estrogen receptor alpha — Estrogen receptor 1 PDB rendering based on 1a52 …   Wikipedia RAR-related orphan receptor alpha — RAR related orphan receptor A PDB rendering based on 1n83 …   Wikipedia Retinoic acid receptor alpha — Retinoic acid receptor, alpha PDB rendering based on 1dkf …   Wikipedia Peroxisome proliferator-activated receptor alpha — PDB rendering based on 1i7g …   Wikipedia Retinoid X receptor alpha — Retinoid X receptor, alpha PDB rendering based on 1by4 …   Wikipedia Liver X receptor alpha — Nuclear receptor subfamily 1, group H, member 3 PDB rendering based on 1uhl …   Wikipedia Estrogen-related receptor alpha — PDB rendering based on 1lo1 …   Wikipedia 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. 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