RORA - Nuclear receptor ROR-alpha - human protein (Function)
 
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RORA »  Nuclear receptor ROR-alpha
 
Protein also known as:  Nuclear receptor subfamily 1 group F member 1.
Gene name:  RORA
Family name: Nuclear hormone receptor » NR1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 81 4
GENE REF ISO

Function

 show evidences
Overview 
Nuclear 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. 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.  
17
  • CuratedUniProtKB
GO molecular function 
Direct ligand regulated sequence-specific DNA binding transcription factor activitydefinition[GO:0098531]  
1
  • IDAUniProtKB
DNA bindingdefinition[GO:0003677]  
3
  • IDAUniProtKB
Ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activitydefinition[GO:0004879] silver  
  • IEAInterPro 2 GO
Oxysterol bindingdefinition[GO:0008142]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
2
  • IPIIntAct
  • IPIUniProtKB
Sequence-specific DNA bindingdefinition[GO:0043565]  
1
  • IDAUniProtKB
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
5
  • IDAUniProtKB
  • IDAMGI
Steroid hormone receptor activitydefinition[GO:0003707] silver  
  • IEAInterPro 2 GO
Transcription coactivator bindingdefinition[GO:0001223]  
2
  • IPIUniProtKB
Transcription corepressor bindingdefinition[GO:0001222]  
1
  • IPIUniProtKB
Transcription factor bindingdefinition[GO:0008134]  
2
  • IPIUniProtKB
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Angiogenesisdefinition[GO:0001525]  
1
  • IMPUniProtKB
Cellular response to hypoxiadefinition[GO:0071456]  
1
  • IMPUniProtKB
Cellular response to steroldefinition[GO:0036315]  
2
  • IDAUniProtKB
Cerebellar granule cell precursor proliferationdefinition[GO:0021930]  
  • ISSOrtholog Curator
Cerebellar Purkinje cell differentiationdefinition[GO:0021702] silver  
  • IEAOrtholog Compara
cGMP metabolic processdefinition[GO:0046068] silver  
  • IEAOrtholog Compara
Circadian regulation of gene expressiondefinition[GO:0032922]  
  • ISSOrtholog Curator
Intracellular receptor signaling pathwaydefinition[GO:0030522]  
1
  • IDAUniProtKB
Muscle cell differentiationdefinition[GO:0042692]  
1
  • IMPUniProtKB
Negative regulation of fat cell differentiationdefinition[GO:0045599]  
  • ISSOrtholog Curator
Negative regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043124]  
1
  • IMPUniProtKB
Negative regulation of inflammatory responsedefinition[GO:0050728]  
1
  • IMPUniProtKB
Nitric oxide biosynthetic processdefinition[GO:0006809] silver  
  • IEAOrtholog Compara
Positive regulation of circadian rhythmdefinition[GO:0042753]  
  • ISSOrtholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IDAMGI
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • IDAUniProtKB
Positive regulation vascular endothelial growth factor productiondefinition[GO:0010575]  
1
  • IMPUniProtKB
Regulation of cholesterol homeostasisdefinition[GO:2000188]  
  • ISSOrtholog Curator
Regulation of glucose metabolic processdefinition[GO:0010906]  
  • ISSOrtholog Curator
Regulation of macrophage activationdefinition[GO:0043030] silver  
  • IEAOrtholog Compara
Regulation of smoothened signaling pathwaydefinition[GO:0008589]  
  • ISSOrtholog Curator
Regulation of steroid metabolic processdefinition[GO:0019218]  
  • ISSOrtholog Curator
Regulation of transcription involved in cell fate commitmentdefinition[GO:0060850]  
  • ISSOrtholog Curator
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • IDAUniProtKB
T-helper 17 cell differentiationdefinition[GO:0072539]  
  • ISSOrtholog Curator
Triglyceride homeostasisdefinition[GO:0070328]  
1
  • IMPUniProtKB
Xenobiotic metabolic processdefinition[GO:0006805]  
  • ISSOrtholog Curator
Pathways 
According to KEGG, this protein belongs to the following pathway:
Circadian rhythm - mammal  hsa04710+6095  
According to Reactome, this protein belongs to the following pathways:
Circadian Clock  REACT_24941  
Gene Expression  REACT_71  
 

Keywords

Biological process 
Biological rhythms  definition   [KW-0090]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Receptor  definition   [KW-0675]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: RAR-related_orphan_receptor_alpha
GenomeRNAi: 6095
PRO: PR:P35398
Chemistry
GuidetoPHARMACOLOGY: 598