RORA - Nuclear receptor ROR-alpha - human protein (Function)
 
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Gene
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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 97 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. 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.  
19
  • UniProtKB
GO molecular function 
Beta-catenin bindingdefinition[GO:0008013] silver  
1
  • Ortholog Compara
Core promoter sequence-specific DNA bindingdefinition[GO:0001046]  
1
  • UniProtKB
Direct ligand regulated sequence-specific DNA binding transcription factor activitydefinition[GO:0098531]  
1
  • UniProtKB
DNA bindingdefinition[GO:0003677]  
3
  • UniProtKB
Ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activitydefinition[GO:0004879] silver  
1
  • InterPro 2 GO
Oxysterol bindingdefinition[GO:0008142]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IntAct
  • UniProtKB
RNA polymerase II regulatory region sequence-specific DNA bindingdefinition[GO:0000977]  
1
  • MGI
Sequence-specific DNA bindingdefinition[GO:0043565]  
1
  • UniProtKB
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
5
  • UniProtKB
  • MGI
Steroid hormone receptor activitydefinition[GO:0003707] silver  
1
  • InterPro 2 GO
Transcription coactivator bindingdefinition[GO:0001223]  
2
  • UniProtKB
Transcription corepressor bindingdefinition[GO:0001222]  
1
  • UniProtKB
Transcription factor bindingdefinition[GO:0008134]  
2
  • UniProtKB
Zinc ion bindingdefinition[GO:0008270] silver  
1
  • InterPro 2 GO
GO biological process 
Angiogenesisdefinition[GO:0001525]  
1
  • UniProtKB
Cellular response to hypoxiadefinition[GO:0071456]  
1
  • UniProtKB
Cellular response to steroldefinition[GO:0036315]  
2
  • UniProtKB
Cerebellar granule cell precursor proliferationdefinition[GO:0021930]  
1
  • Ortholog Curator
Cerebellar Purkinje cell differentiationdefinition[GO:0021702] silver  
1
  • Ortholog Compara
cGMP metabolic processdefinition[GO:0046068] silver  
1
  • Ortholog Compara
Circadian regulation of gene expressiondefinition[GO:0032922]  
1
  • Ortholog Curator
Intracellular receptor signaling pathwaydefinition[GO:0030522]  
1
  • UniProtKB
Muscle cell differentiationdefinition[GO:0042692]  
1
  • UniProtKB
Negative regulation of fat cell differentiationdefinition[GO:0045599]  
1
  • Ortholog Curator
Negative regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043124]  
1
  • UniProtKB
Negative regulation of inflammatory responsedefinition[GO:0050728]  
1
  • UniProtKB
Nitric oxide biosynthetic processdefinition[GO:0006809] silver  
1
  • Ortholog Compara
Positive regulation of circadian rhythmdefinition[GO:0042753]  
1
  • Ortholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
2
  • MGI
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • UniProtKB
Positive regulation of vascular endothelial growth factor productiondefinition[GO:0010575]  
1
  • UniProtKB
Regulation of cholesterol homeostasisdefinition[GO:2000188]  
1
  • Ortholog Curator
Regulation of glucose metabolic processdefinition[GO:0010906]  
1
  • Ortholog Curator
Regulation of macrophage activationdefinition[GO:0043030] silver  
1
  • Ortholog Compara
Regulation of smoothened signaling pathwaydefinition[GO:0008589]  
1
  • Ortholog Curator
Regulation of steroid metabolic processdefinition[GO:0019218]  
1
  • Ortholog Curator
Regulation of transcription involved in cell fate commitmentdefinition[GO:0060850]  
1
  • Ortholog Curator
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • UniProtKB
Steroid hormone mediated signaling pathwaydefinition[GO:0043401] silver  
1
  • InterPro 2 GO
T-helper 17 cell differentiationdefinition[GO:0072539]  
1
  • Ortholog Curator
Triglyceride homeostasisdefinition[GO:0070328]  
1
  • UniProtKB
Xenobiotic metabolic processdefinition[GO:0006805]  
1
  • Ortholog 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:
BMAL1:CLOCK,NPAS2 activates circadian gene expression  REACT_111118  
Circadian Clock  REACT_24941  
Nuclear Receptor transcription pathway  REACT_15525  
PPARA activates gene expression  REACT_116145  
REV-ERBA represses gene expression  REACT_118789  
RORA activates circadian gene expression  REACT_118659  
 

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