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Aliases for RORA Gene

Aliases for RORA Gene

  • RAR-Related Orphan Receptor A 2 3 4
  • Nuclear Receptor Subfamily 1 Group F Member 1 3 4
  • Nuclear Receptor RZR-Alpha 3 4
  • NR1F1 3 4
  • RZRA 3 4
  • Retinoic Acid Receptor-Related Orphan Receptor Alpha 3
  • Thyroid Hormone Nuclear Receptor Alpha Variant 4 3
  • Retinoid-Related Orphan Receptor Alpha 3
  • Retinoid-Related Orphan Receptor-Alpha 4
  • Transcription Factor RZR-Alpha 3
  • Nuclear Receptor ROR-Alpha 3
  • ROR-Alpha 3
  • RZR-ALPHA 3
  • ROR1 3
  • ROR2 3
  • ROR3 3

External Ids for RORA Gene

Summaries for RORA Gene

Entrez Gene Summary for RORA Gene

  • The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, as well as with NM23-1, the product of a tumor metastasis suppressor candidate gene. Also, it has been shown to aid in the transcriptional regulation of some genes involved in circadian rhythm. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2014]

GeneCards Summary for RORA Gene

RORA (RAR-Related Orphan Receptor A) is a Protein Coding gene. Diseases associated with RORA include hypoalphalipoproteinemia. Among its related pathways are GPCR Pathway and Signaling by GPCR. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and steroid hormone receptor activity. An important paralog of this gene is NR1I2.

UniProtKB/Swiss-Prot for RORA Gene

  • 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.

Gene Wiki entry for RORA Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RORA Gene

Genomics for RORA Gene

Genomic Location for RORA Gene

Start:
60,488,284 bp from pter
End:
61,229,319 bp from pter
Size:
741,036 bases
Orientation:
Minus strand

Genomic View for RORA Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for RORA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RORA Gene

Regulatory Elements for RORA Gene

Proteins for RORA Gene

  • Protein details for RORA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35398-RORA_HUMAN
    Recommended name:
    Nuclear receptor ROR-alpha
    Protein Accession:
    P35398
    Secondary Accessions:
    • P35397
    • P35399
    • P45445
    • Q495X4
    • Q96H83

    Protein attributes for RORA Gene

    Size:
    523 amino acids
    Molecular mass:
    58975 Da
    Quaternary structure:
    • Monomer. Interacts (via the DNA-binding domain) with HIF1A; the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interacts with CEBPB; the interaction disrupts the interaction CEBPB:EP300. Interacts with the coactivators NCOA2, PPARGC1A (via LXXLL motif), EP300 and MED1. Interacts with the corepressor NCOR1. Interacts with MAGED1 and CTNNB1. Interacts with CRY1 and PER2. Interacts (via AF-2 motif) with PROX1 (By similarity). Interacts with NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3 (via LXXLL motif).

    Three dimensional structures from OCA and Proteopedia for RORA Gene

    Alternative splice isoforms for RORA Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RORA Gene

Proteomics data for RORA Gene at MOPED

Post-translational modifications for RORA Gene

  • Isoform 1: monomethylated at Lys-38 by EZH2, this creates a degron recognized by a DCX (DDB1-DCAF1/VPRBP-CUL4A-RBX1) E3 ubiquitin ligase complex.
  • Phosphorylation by conventional PKCs in neurons inhibits transcriptional activity. Phosphorylated on Thr-183 by MAPK1/ERK1 in vitro.
  • Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2, PIAS3, PIAS4 but not PIAS1, enhances the transcriptional activity. Desumoylated by SENP1.
  • Ubiquitinated, leading to its degradation by the proteasome. Proteasomal degradation is required for efficient transcriptional activity and is prevented by HR.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for RORA Gene

No data available for DME Specific Peptides for RORA Gene

Domains for RORA Gene

Gene Families for RORA Gene

HGNC:
  • NR :Nuclear hormone receptors
IUPHAR :

UniProtKB/Swiss-Prot:

RORA_HUMAN
Domain:
  • The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs.:
    • P35398
  • Contains 1 nuclear receptor DNA-binding domain.:
    • P35398
Family:
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.:
    • P35398
genes like me logo Genes that share domains with RORA: view

Function for RORA Gene

Molecular function for RORA Gene

GENATLAS Biochemistry: RAR related orphan receptor alpha,ligand activated transcription factor no known ligand,steroid/thyroid nuclear receptor superfamily,interacting with EP300 and MYOD1 in myogenesis
UniProtKB/Swiss-Prot 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. 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.
UniProtKB/Swiss-Prot Induction: Induced by oxidative stress and DNA damage. Isoform 4 is induced by hypoxia (through transactivation by HIF1A and SP1), but not isoform 1.

Gene Ontology (GO) - Molecular Function for RORA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 19955433
GO:0001046 core promoter sequence-specific DNA binding IDA 21628546
GO:0001222 transcription corepressor binding IPI 9328355
GO:0001223 transcription coactivator binding IPI 10478845
GO:0003677 DNA binding IDA 11053433
genes like me logo Genes that share ontologies with RORA: view
genes like me logo Genes that share phenotypes with RORA: view

Animal Models for RORA Gene

MGI Knock Outs for RORA:

miRNA for RORA Gene

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for RORA Gene

Localization for RORA Gene

Subcellular locations from UniProtKB/Swiss-Prot for RORA Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RORA Gene COMPARTMENTS Subcellular localization image for RORA gene
Compartment Confidence
nucleus 5
cytosol 2
extracellular 1

Gene Ontology (GO) - Cellular Components for RORA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 18658046
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with RORA: view

Pathways for RORA Gene

genes like me logo Genes that share pathways with RORA: view

Gene Ontology (GO) - Biological Process for RORA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IMP 18658046
GO:0006351 transcription, DNA-templated --
GO:0006355 regulation of transcription, DNA-templated IDA 9328355
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0006805 xenobiotic metabolic process ISS --
genes like me logo Genes that share ontologies with RORA: view

Compounds for RORA Gene

(2) Drugbank Compounds for RORA Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Cholesterol
57-88-5 target
Cholesterol-Sulfate
target

(3) IUPHAR Ligand for RORA Gene

Ligand Type Action Affinity Pubmed IDs
7-hydroxycholesterol Agonist Agonist
cholesterol sulphate Agonist Agonist
cholesterol Agonist Agonist

(16) Novoseek inferred chemical compound relationships for RORA Gene

Compound -log(P) Hits PubMed IDs
cholesterol-sulfate 73.7 5
retinoic acid 68.7 26
melatonin 64.8 24
thiazolidinedione 55 4
retinoid 46.6 3
genes like me logo Genes that share compounds with RORA: view

Transcripts for RORA Gene

Unigene Clusters for RORA Gene

RAR-related orphan receptor A:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for RORA Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17
SP1: - - - -
SP2: - - - - -
SP3: - - - - - - - -
SP4: - - -
SP5:
SP6: - -

Relevant External Links for RORA Gene

GeneLoc Exon Structure for
RORA
ECgene alternative splicing isoforms for
RORA

Expression for RORA Gene

mRNA expression in normal human tissues for RORA Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RORA Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (6.3), Skin - Not Sun Exposed (Suprapubic) (5.9), and Muscle - Skeletal (5.4).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for RORA Gene

SOURCE GeneReport for Unigene cluster for RORA Gene Hs.560343

mRNA Expression by UniProt/SwissProt for RORA Gene

P35398-RORA_HUMAN
Tissue specificity: Widely expressed in a number of tissues. Expressed in both regulatory T-cells (Treg) and effector T-cells (Teff).
genes like me logo Genes that share expressions with RORA: view

Orthologs for RORA Gene

This gene was present in the common ancestor of animals.

Orthologs for RORA Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RORA 36
  • 99.94 (n)
  • 100 (a)
RORA 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RORA 36
  • 96.24 (n)
  • 99.81 (a)
RORA 37
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RORA 36
  • 96.81 (n)
  • 99.24 (a)
RORA 37
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rora 36
  • 90.88 (n)
  • 97.24 (a)
Rora 16
Rora 37
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RORA 37
  • 98 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RORA 37
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rora 36
  • 89.15 (n)
  • 94.57 (a)
chicken
(Gallus gallus)
Aves RORA 36
  • 88.91 (n)
  • 96.46 (a)
RORALPHA1 37
  • 96 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RORA 37
  • 97 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii roraa 36
  • 78.09 (n)
  • 91.27 (a)
roraa 37
  • 82 (a)
OneToOne
zgc55954 36
fruit fly
(Drosophila melanogaster)
Insecta Hr46 37
  • 20 (a)
OneToMany
Hr46 38
  • 37 (a)
worm
(Caenorhabditis elegans)
Secernentea nhr-23 37
  • 24 (a)
OneToMany
nhr-23 38
  • 33 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 27 (a)
OneToMany
Species with no ortholog for RORA:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for RORA Gene

ENSEMBL:
Gene Tree for RORA (if available)
TreeFam:
Gene Tree for RORA (if available)

Paralogs for RORA Gene

genes like me logo Genes that share paralogs with RORA: view

Variants for RORA Gene

Sequence variations from dbSNP and Humsavar for RORA Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs2691 -- 60,859,766(+) CAGAA(C/G)AGGGT intron-variant
rs100018 -- 60,788,089(+) tgatc(A/G)tgtct intron-variant
rs113168 -- 60,884,577(+) TGAAA(C/G)AGGGA intron-variant
rs171026 -- 60,816,614(+) GTAAA(C/T)AGTat intron-variant
rs180482 -- 60,826,966(+) CATCT(A/T)AGTGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RORA Gene

Variant ID Type Subtype PubMed ID
nsv7266 OTHER Inversion 18451855
dgv2392n71 CNV Loss 21882294
nsv525689 CNV Gain 19592680
nsv527607 CNV Loss 19592680
esv998706 CNV Deletion 20482838
nsv507784 CNV Insertion 20534489
nsv827346 CNV Loss 20364138
nsv525850 CNV Loss 19592680
nsv522462 CNV Loss 19592680
esv2749755 CNV Deletion 23290073
nsv827347 CNV Loss 20364138
esv270651 CNV Insertion 20981092
esv2676310 CNV Deletion 23128226
esv23039 CNV Gain 19812545
dgv342e201 CNV Deletion 23290073
esv2749757 CNV Deletion 23290073
esv2749759 CNV Deletion 23290073
esv2749760 CNV Deletion 23290073
esv1376643 CNV Deletion 17803354
esv2749761 CNV Deletion 23290073
nsv1556 CNV Insertion 18451855
nsv904283 CNV Gain 21882294
esv267886 CNV Insertion 20981092
esv274106 CNV Insertion 20981092
esv1398607 CNV Insertion 17803354
esv33678 CNV Loss 17666407
nsv529007 CNV Gain 19592680
nsv520362 CNV Loss 19592680
dgv451e199 CNV Deletion 23128226
nsv520539 CNV Loss 19592680
nsv518973 CNV Loss 19592680
nsv524148 CNV Loss 19592680
esv273558 CNV Insertion 20981092
esv270738 CNV Insertion 20981092
esv22230 CNV Loss 19812545
esv2520429 CNV Deletion 19546169

Relevant External Links for RORA Gene

HapMap Linkage Disequilibrium report
RORA
Human Gene Mutation Database (HGMD)
RORA

Disorders for RORA Gene

(1) MalaCards Diseases for RORA Gene

Search for RORA Gene in MalaCards »

(9) Novoseek inferred disease relationships for RORA Gene

Disease -log(P) Hits PubMed IDs
atherosclerosis 25.2 7
gastric cancer 19.3 1
inflammation 4.62 4
breast cancer 2.37 6
cardiovascular diseases 0 2

Relevant External Links for RORA

Genetic Association Database (GAD)
RORA
Human Genome Epidemiology (HuGE) Navigator
RORA
genes like me logo Genes that share disorders with RORA: view

No data available for UniProtKB/Swiss-Prot for RORA Gene

Publications for RORA Gene

  1. Transcriptional activation and repression by RORalpha, an orphan nuclear receptor required for cerebellar development. (PMID: 9328355) Harding H.P. … Lazar M.A. (Mol. Endocrinol. 1997) 3 4 23
  2. Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD. (PMID: 9862959) Lau P. … Muscat G.E. (Nucleic Acids Res. 1999) 3 4 23
  3. The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response. (PMID: 11252722) Delerive P. … Staels B. (EMBO Rep. 2001) 3 4 23
  4. Transcriptional regulation of apolipoprotein C-III gene expression by the orphan nuclear receptor RORalpha. (PMID: 11053433) Raspe E. … Staels B. (J. Biol. Chem. 2001) 3 4 23
  5. Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A. (PMID: 14722075) Kallen J. … Fournier B. (J. Biol. Chem. 2004) 3 4 23

Products for RORA Gene

  • Addgene plasmids for RORA

Sources for RORA Gene

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