Retinoic acid receptor alpha

NameRetinoic acid receptor alpha
Synonyms
  • NR1B1
  • Nuclear receptor subfamily 1 group B member 1
  • RAR-alpha
Gene NameRARA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001322|Retinoic acid receptor alpha
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL
TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV
EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK
VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL
DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
Number of residues462
Molecular Weight50770.805
Theoretical pI7.95
GO Classification
Functions
  • protein kinase B binding
  • zinc ion binding
  • steroid hormone receptor activity
  • chromatin DNA binding
  • receptor binding
  • transcription factor activity, sequence-specific DNA binding
  • retinoic acid receptor activity
  • transcription factor binding
  • protein domain specific binding
  • retinoic acid-responsive element binding
  • RNA polymerase II regulatory region sequence-specific DNA binding
  • protein heterodimerization activity
  • transcription corepressor activity
  • enzyme binding
  • transcription coactivator activity
  • retinoic acid binding
  • alpha-actinin binding
  • protein kinase A binding
Processes
  • positive regulation of cell cycle
  • positive regulation of interleukin-4 production
  • negative regulation of translational initiation
  • ureteric bud development
  • cellular response to estrogen stimulus
  • apoptotic cell clearance
  • cellular response to retinoic acid
  • negative regulation of tumor necrosis factor production
  • glandular epithelial cell development
  • signal transduction
  • neural tube closure
  • positive regulation of transcription, DNA-templated
  • growth plate cartilage development
  • positive regulation of interleukin-13 production
  • multicellular organism growth
  • negative regulation of cartilage development
  • positive regulation of interleukin-5 production
  • negative regulation of apoptotic process
  • positive regulation of binding
  • Sertoli cell fate commitment
  • positive regulation of transcription from RNA polymerase II promoter
  • negative regulation of granulocyte differentiation
  • trachea cartilage development
  • chondroblast differentiation
  • protein phosphorylation
  • spermatogenesis
  • negative regulation of transcription, DNA-templated
  • positive regulation of cell proliferation
  • positive regulation of T-helper 2 cell differentiation
  • retinoic acid receptor signaling pathway
  • negative regulation of interferon-gamma production
  • ventricular cardiac muscle cell differentiation
  • limb development
  • negative regulation of transcription from RNA polymerase II promoter
  • gene expression
  • cellular response to lipopolysaccharide
  • transcription initiation from RNA polymerase II promoter
  • face development
  • embryonic camera-type eye development
  • response to retinoic acid
  • outflow tract septum morphogenesis
  • germ cell development
Components
  • nucleoplasm
  • cytoplasm
  • nuclear chromatin
  • nucleus
  • dendrite
  • cell surface
  • actin cytoskeleton
  • neuronal cell body
General FunctionZinc ion binding
Specific FunctionReceptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID36157
UniProtKB IDP10276
UniProtKB Entry NameRARA_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0016168|Retinoic acid receptor alpha (RARA)
ATGGCCAGCAACAGCAGCTCCTGCCCGACACCTGGGGGCGGGCACCTCAATGGGTACCCG
GTGCCTCCCTACGCCTTCTTCTTCCCCCCTATGCTGGGTGGACTCTCCCCGCCAGGCGCT
CTGACCACTCTCCAGCACCAGCTTCCAGTTAGTGGATATAGCACACCATCCCCAGCCACC
ATTGAGACCCAGAGCAGCAGTTCTGAAGAGATAGTGCCCAGCCCTCCCTCGCCACCCCCT
CTACCCCGCATCTACAAGCCTTGCTTTGTCTGTCAGGACAAGTCCTCAGGCTACCACTAT
GGGGTCAGCGCCTGTGAGGGCTGCAAGGGCTTCTTCCGCCGCAGCATCCAGAAGAACATG
GTGTACACGTGTCACCGGGACAAGAACTGCATCATCAACAAGGTGACCCGGAACCGCTGC
CAGTACTGCCGACTGCAGAAGTGCTTTGAAGTGGGCATGTCCAAGGAGTCTGTGAGAAAC
GACCGAAACAAGAAGAAGAAGGAGGTGCCCAAGCCCGAGTGCTCTGAGAGCTACACGCTG
ACGCCGGAGGTGGGGGAGCTCATTGAGAAGGTGCGCAAAGCGCACCAGGAAACCTTCCCT
GCCCTCTGCCAGCTGGGCAAATACACTACGAACAACAGCTCAGAACAACGTGTCTCTCTG
GACATTGACCTCTGGGACAAGTTCAGTGAACTCTCCACCAAGTGCATCATTAAGACTGTG
GAGTTCGCCAAGCAGCTGCCCGGCTTCACCACCCTCACCATCGCCGACCAGATCACCCTC
CTCAAGGCTGCCTGCCTGGACATCCTGATCCTGCGGATCTGCACGCGGTACACGCCCGAG
CAGGACACCATGACCTTCTCGGACGGGCTGACCCTGAACCGGACCCAGATGCACAACGCT
GGCTTCGGCCCCCTCACCGACCTGGTCTTTGCCTTCGCCAACCAGCTGCTGCCCCTGGAG
ATGGATGATGCGGAGACGGGGCTGCTCAGCGCCATCTGCCTCATCTGCGGAGACCGCCAG
GACCTGGAGCAGCCGGACCGGGTGGACATGCTGCAGGAGCCGCTGCTGGAGGCGCTAAAG
GTCTACGTGCGGAAGCGGAGGCCCAGCCGCCCCCACATGTTCCCCAAGATGCTAATGAAG
ATTACTGACCTGCGAAGCATCAGCGCCAAGGGGGCTGAGCGGGTGATCACGCTGAAGATG
GAGATCCCGGGCTCCATGCCGCCTCTCATCCAGGAAATGTTGGAGAACTCAGAGGGCCTG
GACACTCTGAGCGGACAGCCGGGGGGTGGGGGGCGGGACGGGGGTGGCCTGGCCCCCCCG
CCAGGCAGCTGTAGCCCCAGCCTCAGCCCCAGCTCCAACAGAAGCAGCCCGGCCACCCAC
TCCCCGTGA
GenBank Gene IDX06614
GeneCard IDNot Available
GenAtlas IDRARA
HGNC IDHGNC:9864
Chromosome Location17
Locus17q21
References
  1. Giguere V, Ong ES, Segui P, Evans RM: Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17-23;330(6149):624-9. 2825036
  2. Chen Z, Guidez F, Rousselot P, Agadir A, Chen SJ, Wang ZY, Degos L, Zelent A, Waxman S, Chomienne C: PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1178-82. 8302850
  3. Hjalt TA, Murray JC: Genomic structure of the human retinoic acid receptor-alpha1 gene. Mamm Genome. 1999 May;10(5):528-9. 10337631
  4. Parrado A, Despouy G, Kraiba R, Le Pogam C, Dupas S, Choquette M, Robledo M, Larghero J, Bui H, Le Gall I, Rochette-Egly C, Chomienne C, Padua RA: Retinoic acid receptor alpha1 variants, RARalpha1DeltaB and RARalpha1DeltaBC, define a new class of nuclear receptor isoforms. Nucleic Acids Res. 2001 Dec 15;29(24):4901-8. 11812818
  5. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. 16625196
  6. 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. 15489334
  7. Brand NJ, Petkovich M, Chambon P: Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha). Nucleic Acids Res. 1990 Dec 11;18(23):6799-806. 2175878
  8. Petkovich M, Brand NJ, Krust A, Chambon P: A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3-9;330(6147):444-50. 2825025
  9. Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ: The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood. 1996 Feb 1;87(3):882-6. 8562957
  10. Fujita K, Oba R, Harada H, Mori H, Niikura H, Isoyama K, Omine M: Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: structure of the fusion point in a case lacking classic t(15;17) translocation. Leuk Lymphoma. 2003 Jan;44(1):111-5. 12691149
  11. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. 9267036
  12. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. 10567404
  13. Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ: Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. J Biol Chem. 2002 Aug 9;277(32):28624-30. Epub 2002 May 30. 12039952
  14. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. 11971969
  15. Kim YE, Kim DY, Lee JM, Kim ST, Han TH, Ahn JH: Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation. Biochem Biophys Res Commun. 2005 May 13;330(3):746-54. 15809060
  16. Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R: The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005 Sep 23;122(6):835-47. 16179254
  17. Srinivas H, Xia D, Moore NL, Uray IP, Kim H, Ma L, Weigel NL, Brown PH, Kurie JM: Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha. Biochem J. 2006 May 1;395(3):653-62. 16417524
  18. Cho YS, Kim EJ, Park UH, Sin HS, Um SJ: Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor. J Biol Chem. 2006 Jun 30;281(26):17588-98. Epub 2006 Apr 10. 16606617
  19. Li HJ, Haque ZK, Chen A, Mendelsohn M: RIF-1, a novel nuclear receptor corepressor that associates with the nuclear matrix. J Cell Biochem. 2007 Nov 1;102(4):1021-35. 17455211
  20. Zhu L, Santos NC, Kim KH: Small ubiquitin-like modifier-2 modification of retinoic acid receptor-alpha regulates its subcellular localization and transcriptional activity. Endocrinology. 2009 Dec;150(12):5586-95. doi: 10.1210/en.2009-0868. Epub 2009 Oct 22. 19850744
  21. Fujiki R, Chikanishi T, Hashiba W, Ito H, Takada I, Roeder RG, Kitagawa H, Kato S: GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature. 2009 May 21;459(7245):455-9. doi: 10.1038/nature07954. Epub 2009 Apr 19. 19377461
  22. Santos NC, Kim KH: Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar 9. 20215566
  23. Khurana S, Chakraborty S, Lam M, Liu Y, Su YT, Zhao X, Saleem MA, Mathieson PW, Bruggeman LA, Kao HY: Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors. J Biol Chem. 2012 Apr 6;287(15):12027-35. doi: 10.1074/jbc.M112.345421. Epub 2012 Feb 17. 22351778
  24. Rastinejad F, Wagner T, Zhao Q, Khorasanizadeh S: Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1. EMBO J. 2000 Mar 1;19(5):1045-54. 10698945
  25. Bourguet W, Vivat V, Wurtz JM, Chambon P, Gronemeyer H, Moras D: Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains. Mol Cell. 2000 Feb;5(2):289-98. 10882070
  26. le Maire A, Teyssier C, Erb C, Grimaldi M, Alvarez S, de Lera AR, Balaguer P, Gronemeyer H, Royer CA, Germain P, Bourguet W: A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor. Nat Struct Mol Biol. 2010 Jul;17(7):801-7. doi: 10.1038/nsmb.1855. Epub 2010 Jun 13. 20543827