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Identification
HMDB Protein ID HMDBP02591
Secondary Accession Numbers
  • 8090
Name Nuclear receptor ROR-alpha
Synonyms
  1. Nuclear receptor RZR-alpha
  2. Nuclear receptor subfamily 1 group F member 1
  3. Retinoid-related orphan receptor-alpha
Gene Name RORA
Protein Type Enzyme
Biological Properties
General Function Involved in sequence-specific DNA binding transcription factor activity
Specific Function Orphan nuclear receptor. Binds DNA as a monomer to hormone response elements (HRE) containing a single core motif half-site preceded by a short A-T-rich sequence. This isomer binds to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'. Regulates a number of genes involved in lipid metabolism such as apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in cerebellum and photoreceptor development including PCP2, OPN1SW, OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal muscle development with MYOD1. Possible receptor for cholesterol or one of its derivatives
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
ion binding
cation binding
metal ion binding
binding
transition metal ion binding
zinc ion binding
receptor activity
molecular transducer activity
signal transducer activity
nucleic acid binding
dna binding
sequence-specific dna binding
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
sequence-specific dna binding transcription factor activity
Process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
regulation of transcription, dna-dependent
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location Chromosome:1
Locus 15q22.2
SNPs RORA
Gene Sequence
>1671 bp
ATGAATGAGGGGGCCCCAGGAGACAGTGACTTAGAGACTGAGGCAAGAGTGCCGTGGTCA
ATCATGGGTCATTGTCTTCGAACTGGACAGGCCAGAATGTCTGCCACACCCACACCTGCA
GGTGAAGGAGCCAGAAGGGATGAACTTTTTGGGATTCTCCAAATACTCCATCAGTGTATC
CTGTCTTCAGGTGATGCTTTTGTTCTTACTGGCGTCTGTTGTTCCTGGAGGCAGAATGGC
AAGCCACCATATTCACAAAAGGAAGATAAGGAAGTACAAACTGGATACATGAATGCTCAA
ATTGAAATTATTCCATGCAAGATCTGTGGAGACAAATCATCAGGAATCCATTATGGTGTC
ATTACATGTGAAGGCTGCAAGGGCTTTTTCAGGAGAAGTCAGCAAAGCAATGCCACCTAC
TCCTGTCCTCGTCAGAAGAACTGTTTGATTGATCGAACCAGTAGAAACCGCTGCCAACAC
TGTCGATTACAGAAATGCCTTGCCGTAGGGATGTCTCGAGATGCTGTAAAATTTGGCCGA
ATGTCAAAAAAGCAGAGAGACAGCTTGTATGCAGAAGTACAGAAACACCGGATGCAGCAG
CAGCAGCGCGACCACCAGCAGCAGCCTGGAGAGGCTGAGCCGCTGACGCCCACCTACAAC
ATCTCGGCCAACGGGCTGACGGAACTTCACGACGACCTCAGTAACTACATTGACGGGCAC
ACCCCTGAGGGGAGTAAGGCAGACTCCGCCGTCAGCAGCTTCTACCTGGACATACAGCCT
TCCCCAGACCAGTCAGGTCTTGATATCAATGGAATCAAACCAGAACCAATATGTGACTAC
ACACCAGCATCAGGCTTCTTTCCCTACTGTTCGTTCACCAACGGCGAGACTTCCCCAACT
GTGTCCATGGCAGAATTAGAACACCTTGCACAGAATATATCTAAATCGCATCTGGAAACC
TGCCAATACTTGAGAGAAGAGCTCCAGCAGATAACGTGGCAGACCTTTTTACAGGAAGAA
ATTGAGAACTATCAAAACAAGCAGCGGGAGGTGATGTGGCAATTGTGTGCCATCAAAATT
ACAGAAGCTATACAGTATGTGGTGGAGTTTGCCAAACGCATTGATGGATTTATGGAACTG
TGTCAAAATGATCAAATTGTGCTTCTAAAAGCAGGTTCTCTAGAGGTGGTGTTTATCAGA
ATGTGCCGTGCCTTTGACTCTCAGAACAACACCGTGTACTTTGATGGGAAGTATGCCAGC
CCCGACGTCTTCAAATCCTTAGGTTGTGAAGACTTTATTAGCTTTGTGTTTGAATTTGGA
AAGAGTTTATGTTCTATGCACCTGACTGAAGATGAAATTGCATTATTTTCTGCATTTGTA
CTGATGTCAGCAGATCGCTCATGGCTGCAAGAAAAGGTAAAAATTGAAAAACTGCAACAG
AAAATTCAGCTAGCTCTTCAACACGTCCTACAGAAGAATCACCGAGAAGATGGAATACTA
ACAAAGTTAATATGCAAGGTGTCTACATTAAGAGCCTTATGTGGACGACATACAGAAAAG
CTAATGGCATTTAAAGCAATATACCCAGACATTGTGCGACTTCATTTTCCTCCATTATAC
AAGGAGTTGTTCACTTCAGAATTTGAGCCAGCAATGCAAATTGATGGGTAA
Protein Properties
Number of Residues 556
Molecular Weight 63035.2
Theoretical pI 6.34
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Nuclear receptor ROR-alpha
MNEGAPGDSDLETEARVPWSIMGHCLRTGQARMSATPTPAGEGARRDELFGILQILHQCI
LSSGDAFVLTGVCCSWRQNGKPPYSQKEDKEVQTGYMNAQIEIIPCKICGDKSSGIHYGV
ITCEGCKGFFRRSQQSNATYSCPRQKNCLIDRTSRNRCQHCRLQKCLAVGMSRDAVKFGR
MSKKQRDSLYAEVQKHRMQQQQRDHQQQPGEAEPLTPTYNISANGLTELHDDLSNYIDGH
TPEGSKADSAVSSFYLDIQPSPDQSGLDINGIKPEPICDYTPASGFFPYCSFTNGETSPT
VSMAELEHLAQNISKSHLETCQYLREELQQITWQTFLQEEIENYQNKQREVMWQLCAIKI
TEAIQYVVEFAKRIDGFMELCQNDQIVLLKAGSLEVVFIRMCRAFDSQNNTVYFDGKYAS
PDVFKSLGCEDFISFVFEFGKSLCSMHLTEDEIALFSAFVLMSADRSWLQEKVKIEKLQQ
KIQLALQHVLQKNHREDGILTKLICKVSTLRALCGRHTEKLMAFKAIYPDIVRLHFPPLY
KELFTSEFEPAMQIDG
GenBank ID Protein 19743901
UniProtKB/Swiss-Prot ID P35398
UniProtKB/Swiss-Prot Entry Name RORA_HUMAN
PDB IDs
GenBank Gene ID NM_134260.2
GeneCard ID RORA
GenAtlas ID RORA
HGNC ID HGNC:10258
References
General References
  1. 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. [PubMed:15489334 ]
  2. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  3. Giguere V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G: Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev. 1994 Mar 1;8(5):538-53. [PubMed:7926749 ]
  4. Becker-Andre M, Andre E, DeLamarter JF: Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1371-9. [PubMed:7916608 ]
  5. Lau P, Bailey P, Dowhan DH, Muscat GE: Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD. Nucleic Acids Res. 1999 Jan 15;27(2):411-20. [PubMed:9862959 ]
  6. Sundvold H, Lien S: Identification of a novel peroxisome proliferator-activated receptor (PPAR) gamma promoter in man and transactivation by the nuclear receptor RORalpha1. Biochem Biophys Res Commun. 2001 Sep 21;287(2):383-90. [PubMed:11554739 ]
  7. Raspe E, Duez H, Gervois P, Fievet C, Fruchart JC, Besnard S, Mariani J, Tedgui A, Staels B: Transcriptional regulation of apolipoprotein C-III gene expression by the orphan nuclear receptor RORalpha. J Biol Chem. 2001 Jan 26;276(4):2865-71. Epub 2000 Oct 26. [PubMed:11053433 ]
  8. Moraitis AN, Giguere V: The co-repressor hairless protects RORalpha orphan nuclear receptor from proteasome-mediated degradation. J Biol Chem. 2003 Dec 26;278(52):52511-8. Epub 2003 Oct 21. [PubMed:14570920 ]
  9. Genoux A, Dehondt H, Helleboid-Chapman A, Duhem C, Hum DW, Martin G, Pennacchio LA, Staels B, Fruchart-Najib J, Fruchart JC: Transcriptional regulation of apolipoprotein A5 gene expression by the nuclear receptor RORalpha. Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1186-92. Epub 2005 Mar 24. [PubMed:15790933 ]
  10. Lind U, Nilsson T, McPheat J, Stromstedt PE, Bamberg K, Balendran C, Kang D: Identification of the human ApoAV gene as a novel RORalpha target gene. Biochem Biophys Res Commun. 2005 Apr 29;330(1):233-41. [PubMed:15781255 ]
  11. Lechtken A, Hornig M, Werz O, Corvey N, Zundorf I, Dingermann T, Brandes R, Steinhilber D: Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro. Biochem Biophys Res Commun. 2007 Jul 6;358(3):890-6. Epub 2007 May 11. [PubMed:17512500 ]
  12. Kim EJ, Yoo YG, Yang WK, Lim YS, Na TY, Lee IK, Lee MO: Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling. Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1796-802. doi: 10.1161/ATVBAHA.108.171546. Epub 2008 Jul 24. [PubMed:18658046 ]
  13. Duplus E, Gras C, Soubeyre V, Vodjdani G, Lemaigre-Dubreuil Y, Brugg B: Phosphorylation and transcriptional activity regulation of retinoid-related orphan receptor alpha 1 by protein kinases C. J Neurochem. 2008 Mar;104(5):1321-32. Epub 2007 Nov 10. [PubMed:18005000 ]
  14. Hwang EJ, Lee JM, Jeong J, Park JH, Yang Y, Lim JS, Kim JH, Baek SH, Kim KI: SUMOylation of RORalpha potentiates transcriptional activation function. Biochem Biophys Res Commun. 2009 Jan 16;378(3):513-7. doi: 10.1016/j.bbrc.2008.11.072. Epub 2008 Nov 28. [PubMed:19041634 ]
  15. Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B: X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Structure. 2002 Dec;10(12):1697-707. [PubMed:12467577 ]
  16. Kallen J, Schlaeppi JM, Bitsch F, Delhon I, Fournier B: Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A. J Biol Chem. 2004 Apr 2;279(14):14033-8. Epub 2004 Jan 13. [PubMed:14722075 ]