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NameNuclear receptor ROR-alpha
Synonyms
  • NR1F1
  • Nuclear receptor RZR-alpha
  • Nuclear receptor subfamily 1 group F member 1
  • RAR-related orphan receptor A
  • Retinoid-related orphan receptor-alpha
  • RZRA
Gene NameRORA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009466|Nuclear receptor ROR-alpha
MESAPAAPDPAASEPGSSGADAAAGSRETPLNQESARKSEPPAPVRRQSYSSTSRGISVT
KKTHTSQIEIIPCKICGDKSSGIHYGVITCEGCKGFFRRSQQSNATYSCPRQKNCLIDRT
SRNRCQHCRLQKCLAVGMSRDAVKFGRMSKKQRDSLYAEVQKHRMQQQQRDHQQQPGEAE
PLTPTYNISANGLTELHDDLSNYIDGHTPEGSKADSAVSSFYLDIQPSPDQSGLDINGIK
PEPICDYTPASGFFPYCSFTNGETSPTVSMAELEHLAQNISKSHLETCQYLREELQQITW
QTFLQEEIENYQNKQREVMWQLCAIKITEAIQYVVEFAKRIDGFMELCQNDQIVLLKAGS
LEVVFIRMCRAFDSQNNTVYFDGKYASPDVFKSLGCEDFISFVFEFGKSLCSMHLTEDEI
ALFSAFVLMSADRSWLQEKVKIEKLQQKIQLALQHVLQKNHREDGILTKLICKVSTLRAL
CGRHTEKLMAFKAIYPDIVRLHFPPLYKELFTSEFEPAMQIDG
Number of residues523
Molecular Weight58974.35
Theoretical pINot Available
GO Classification
Functions
  • transcription coactivator binding
  • transcription corepressor binding
  • zinc ion binding
  • steroid hormone receptor activity
  • DNA binding
  • transcription factor binding
  • oxysterol binding
  • sequence-specific DNA binding
  • transcription factor activity, direct ligand regulated sequence-specific DNA binding
  • transcription factor activity, sequence-specific DNA binding
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
  • core promoter sequence-specific DNA binding
  • RNA polymerase II regulatory region sequence-specific DNA binding
Processes
  • regulation of glucose metabolic process
  • positive regulation of transcription, DNA-templated
  • regulation of smoothened signaling pathway
  • positive regulation of transcription from RNA polymerase II promoter
  • cGMP metabolic process
  • negative regulation of I-kappaB kinase/NF-kappaB signaling
  • circadian rhythm
  • circadian regulation of gene expression
  • negative regulation of inflammatory response
  • cellular response to interleukin-1
  • angiogenesis
  • cerebellar granule cell precursor proliferation
  • xenobiotic metabolic process
  • regulation of transcription involved in cell fate commitment
  • triglyceride homeostasis
  • negative regulation of fat cell differentiation
  • cellular response to hypoxia
  • positive regulation of vascular endothelial growth factor production
  • gene expression
  • cellular response to sterol
  • intracellular receptor signaling pathway
  • transcription initiation from RNA polymerase II promoter
  • positive regulation of circadian rhythm
  • regulation of macrophage activation
  • regulation of steroid metabolic process
  • muscle cell differentiation
  • T-helper 17 cell differentiation
  • nitric oxide biosynthetic process
  • regulation of transcription, DNA-templated
  • cerebellar Purkinje cell differentiation
  • cellular response to tumor necrosis factor
  • regulation of cholesterol homeostasis
Components
  • nucleus
  • nucleoplasm
General FunctionZinc ion binding
Specific FunctionNuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP35398
UniProtKB Entry NameRORA_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0021397|Nuclear receptor ROR-alpha (RORA)
ATGAATGAGGGGGCCCCAGGAGACAGTGACTTAGAGACTGAGGCAAGAGTGCCGTGGTCA
ATCATGGGTCATTGTCTTCGAACTGGACAGGCCAGAATGTCTGCCACACCCACACCTGCA
GGTGAAGGAGCCAGAAGCTCTTCAACCTGTAGCTCCCTGAGCAGGCTGTTCTGGTCTCAA
CTTGAGCACATAAACTGGGATGGAGCCACAGCCAAGAACTTTATTAATTTAAGGGAGTTC
TTCTCTTTTCTGCTCCCTGCATTGAGAAAAGCTCAAATTGAAATTATTCCATGCAAGATC
TGTGGAGACAAATCATCAGGAATCCATTATGGTGTCATTACATGTGAAGGCTGCAAGGGC
TTTTTCAGGAGAAGTCAGCAAAGCAATGCCACCTACTCCTGTCCTCGTCAGAAGAACTGT
TTGATTGATCGAACCAGTAGAAACCGCTGCCAACACTGTCGATTACAGAAATGCCTTGCC
GTAGGGATGTCTCGAGATGCTGTAAAATTTGGCCGAATGTCAAAAAAGCAGAGAGACAGC
TTGTATGCAGAAGTACAGAAACACCGGATGCAGCAGCAGCAGCGCGACCACCAGCAGCAG
CCTGGAGAGGCTGAGCCGCTGACGCCCACCTACAACATCTCGGCCAACGGGCTGACGGAA
CTTCACGACGACCTCAGTAACTACATTGACGGGCACACCCCTGAGGGGAGTAAGGCAGAC
TCCGCCGTCAGCAGCTTCTACCTGGACATACAGCCTTCCCCAGACCAGTCAGGTCTTGAT
ATCAATGGAATCAAACCAGAACCAATATGTGACTACACACCAGCATCAGGCTTCTTTCCC
TACTGTTCGTTCACCAACGGCGAGACTTCCCCAACTGTGTCCATGGCAGAATTAGAACAC
CTTGCACAGAATATATCTAAATCGCATCTGGAAACCTGCCAATACTTGAGAGAAGAGCTC
CAGCAGATAACGTGGCAGACCTTTTTACAGGAAGAAATTGAGAACTATCAAAACAAGCAG
CGGGAGGTGATGTGGCAATTGTGTGCCATCAAAATTACAGAAGCTATACAGTATGTGGTG
GAGTTTGCCAAACGCATTGATGGATTTATGGAACTGTGTCAAAATGATCAAATTGTGCTT
CTAAAAGCAGGTTCTCTAGAGGTGGTGTTTATCAGAATGTGCCGTGCCTTTGACTCTCAG
AACAACACCGTGTACTTTGATGGGAAGTATGCCAGCCCCGACGTCTTCAAATCCTTAGGT
TGTGAAGACTTTATTAGCTTTGTGTTTGAATTTGGAAAGAGTTTATGTTCTATGCACCTG
ACTGAAGATGAAATTGCATTATTTTCTGCATTTGTACTGATGTCAGCAGATCGCTCATGG
CTGCAAGAAAAGGTAAAAATTGAAAAACTGCAACAGAAAATTCAGCTAGCTCTTCAACAC
GTCCTACAGAAGAATCACCGAGAAGATGGAATACTAACAAAGTTAATATGCAAGGTGTCT
ACATTAAGAGCCTTATGTGGACGACATACAGAAAAGCTAATGGCATTTAAAGCAATATAC
CCAGACATTGTGCGACTTCATTTTCCTCCATTATACAAGGAGTTGTTCACTTCAGAATTT
GAGCCAGCAATGCAAATTGATGGGTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:10258
Chromosome Location15
LocusNot Available
References
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