Homo sapiens Protein: RORA
InnateDB Protein IDBP-14926.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol RORA
Protein Name RAR-related orphan receptor A
Synonyms NR1F1; ROR1; ROR2; ROR3; RZR-ALPHA; RZRA;
Species Homo sapiens
Ensembl Protein ENSP00000335087
InnateDB Gene IDBG-14920 (RORA)
Protein Structure
UniProt Annotation
Function 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. {ECO:0000269PubMed:10478845, ECO:0000269PubMed:11053433, ECO:0000269PubMed:11252722, ECO:0000269PubMed:11554739, ECO:0000269PubMed:12467577, ECO:0000269PubMed:14570920, ECO:0000269PubMed:15781255, ECO:0000269PubMed:15790933, ECO:0000269PubMed:16462772, ECO:0000269PubMed:17512500, ECO:0000269PubMed:18005000, ECO:0000269PubMed:18658046, ECO:0000269PubMed:19965867, ECO:0000269PubMed:21499262, ECO:0000269PubMed:7926749, ECO:0000269PubMed:9328355, ECO:0000269PubMed:9862959}.
Subcellular Localization Nucleus {ECO:0000255PROSITE- ProRule:PRU00407, ECO:0000269PubMed:18005000, ECO:0000269PubMed:18658046}.
Disease Associations
Tissue Specificity Widely expressed in a number of tissues. {ECO:0000269PubMed:7916608}.
Number of Interactions This gene and/or its encoded proteins are associated with 40 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.
Experimentally validated
Total 40 [view]
Protein-Protein 38 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 2 [view]
Predicted by orthology
Total 4 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001222 transcription corepressor binding
GO:0001223 transcription coactivator binding
GO:0003677 DNA binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0003707 steroid hormone receptor activity
GO:0004879 ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0008142 oxysterol binding
GO:0008270 zinc ion binding
GO:0043565 sequence-specific DNA binding
GO:0098531 direct ligand regulated sequence-specific DNA binding transcription factor activity
Biological Process
GO:0001525 angiogenesis
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0006805 xenobiotic metabolic process
GO:0008589 regulation of smoothened signaling pathway
GO:0010467 gene expression
GO:0010575 positive regulation vascular endothelial growth factor production
GO:0010906 regulation of glucose metabolic process
GO:0019218 regulation of steroid metabolic process
GO:0021930 cerebellar granule cell precursor proliferation
GO:0030522 intracellular receptor signaling pathway
GO:0032922 circadian regulation of gene expression
GO:0036315 cellular response to sterol
GO:0042692 muscle cell differentiation
GO:0042753 positive regulation of circadian rhythm
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043401 steroid hormone mediated signaling pathway
GO:0045087 innate immune response (InnateDB)
GO:0045599 negative regulation of fat cell differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050728 negative regulation of inflammatory response
GO:0060850 regulation of transcription involved in cell fate commitment
GO:0070328 triglyceride homeostasis
GO:0071456 cellular response to hypoxia
GO:0072539 T-helper 17 cell differentiation
GO:2000188 regulation of cholesterol homeostasis
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
Protein Structure and Domains
InterPro IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001628 Zinc finger, nuclear hormone receptor-type
IPR001723 Steroid hormone receptor
IPR001728 Thyroid hormone receptor
IPR003079 Nuclear receptor ROR
IPR008946 Nuclear hormone receptor, ligand-binding
PFAM PF00104
Post-translational Modifications
SwissProt P35398
PhosphoSite PhosphoSite-P35398
UniProt Splice Variant
Entrez Gene 6095
UniGene Hs.718317
RefSeq NP_599023
OMIM 600825
HPRD 02896
EMBL AC009560 AC012404 AC022898 AC079068 AC087385 AC107241 AC107905 BC008831 BC100987 BC100988 BC100989 BC100990 CH471082 HQ692818 L14611 U04897 U04898 U04899
GenPept AAA02963 AAA62658 AAA62659 AAA62660 AAH08831 AAI00988 AAI00989 AAI00990 AAI00991 ADZ17329 EAW77594