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P35398 (RORA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor ROR-alpha
Alternative name(s):
Nuclear receptor RZR-alpha
Nuclear receptor subfamily 1 group F member 1
RAR-related orphan receptor A
Retinoid-related orphan receptor-alpha
Gene names
Name:RORA
Synonyms:NR1F1, RZRA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length523 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23 Ref.24 Ref.28

Subunit 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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.19

Subcellular location

Nucleus Ref.19 Ref.20.

Tissue specificity

Widely expressed in a number of tissues. Ref.2

Induction

Induced by oxidative stress and DNA damage. Isoform 4 is induced by hypoxia (through transactivation by HIF1A and SP1), but not isoform 1. Ref.14 Ref.17 Ref.19

Domain

The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs By similarity.

Post-translational modification

Phosphorylation by conventional PKCs in neurons inhibits transcriptional activity. Phosphorylated on Thr-183 by MAPK1/ERK1 in vitro. Ref.18 Ref.20

Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2, PIAS3, PIAS4 but not PIAS1, enhances the transcriptional activity. Desumoylated by SENP1. Ref.21

Ubiquitinated, leading to its degradation by the proteasome. Proteasomal degradation is required for efficient transcriptional activity and is prevented by HR. Ref.13

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. Ref.25

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processBiological rhythms
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative promoter usage
Alternative splicing
Polymorphism
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Receptor
   PTMIsopeptide bond
Methylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT-helper 17 cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

cGMP metabolic process

Inferred from electronic annotation. Source: Ensembl

cellular response to sterol

Inferred from direct assay Ref.23. Source: UniProtKB

cerebellar Purkinje cell differentiation

Inferred from electronic annotation. Source: Ensembl

circadian regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

intracellular receptor signaling pathway

Inferred from direct assay Ref.23. Source: UniProtKB

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype Ref.11. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of inflammatory response

Inferred from mutant phenotype Ref.11. Source: UniProtKB

nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17545671. Source: MGI

regulation of glucose metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of macrophage activation

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.19Ref.23. Source: UniProtKB

   Molecular_functiondirect ligand regulated sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.23. Source: UniProtKB

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from electronic annotation. Source: InterPro

oxysterol binding

Inferred from direct assay Ref.23. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay. Source: MGI

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription coactivator binding

Inferred from physical interaction Ref.8Ref.9. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NR0B1P518432EBI-748689,EBI-946109

Alternative products

This entry describes 4 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35398-2)

Also known as: Alpha-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P35398-1)

Also known as: Alpha-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: MESAPAAPDP...ISVTKKTHTS → MNEGAPGDSD...KEVQTGYMNA
Note: Produced by alternative promoter usage. Region from 23 to 71 inhibits DNA-binding and transactivation activity.
Isoform 3 (identifier: P35398-3)

Also known as: Alpha-3;

The sequence of this isoform differs from the canonical sequence as follows:
     38-65: KSEPPAPVRRQSYSSTSRGISVTKKTHT → SSSTCSSLSRLFWSQLEHINWDGATAKNFINLREFFSFLLPALRK
Note: Produced by alternative splicing.
Isoform 4 (identifier: P35398-4)

Also known as: Alpha-4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: MESAPAAPDPAASEPGSSGADAAAGSRETPLNQESARKSEPPAPVRRQSYSSTSRGISVTKKTHT → MMYFVIAAMK
Note: Produced by alternative promoter usage.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 523523Nuclear receptor ROR-alpha
PRO_0000053512

Regions

DNA binding73 – 13866Nuclear receptor Ref.1 Ref.7 Ref.10 Ref.12 Ref.15 Ref.16
Zinc finger73 – 9321NR C4-type
Zinc finger109 – 13325NR C4-type
Region139 – 271133Hinge
Region272 – 523252Ligand-binding
Motif506 – 52318AF-2
Compositional bias166 – 1694Poly-Gln

Amino acid modifications

Modified residue381N6-methyllysine Ref.25
Modified residue1831Phosphothreonine; by MAPK1
Cross-link240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.21

Natural variations

Alternative sequence1 – 6666MESAP…KTHTS → MNEGAPGDSDLETEARVPWS IMGHCLRTGQARMSATPTPA GEGARRDELFGILQILHQCI LSSGDAFVLTGVCCSWRQNG KPPYSQKEDKEVQTGYMNA in isoform 2.
VSP_053973
Alternative sequence1 – 6565MESAP…KKTHT → MMYFVIAAMK in isoform 4.
VSP_053974
Alternative sequence38 – 6528KSEPP…KKTHT → SSSTCSSLSRLFWSQLEHIN WDGATAKNFINLREFFSFLL PALRK in isoform 3.
VSP_053975
Isoform 2:
Natural variant181P → S in a colorectal cancer sample, somatic mutation.

Experimental info

Mutagenesis1831T → A: Greatly increased transcriptional activity. Decrease in repression by NR1D1. Ref.18
Mutagenesis1831T → D or E: Some increase in transcriptional activity. No change in repression by NR1D1. Ref.18
Mutagenesis1831T → R: Attenuates transcriptional activity. Ref.18
Mutagenesis1831T → V or I: Some increase in transcriptional activity. Ref.18
Mutagenesis2401K → R: Loss of sumoylation. Ref.21
Mutagenesis2881C → Q: Less effect on transcriptional activity with cholesterol sulfate as substrate as compared to cholesterol as substrate. Ref.29
Mutagenesis3231C → L: About 60% loss of transcriptional activity. Ref.28 Ref.29
Mutagenesis3301A → L: About 80% loss of transcriptional activity. Ref.28 Ref.29
Mutagenesis3351V → R: Strongly decreases interaction with NCOA2 and MED1. Ref.8
Mutagenesis3391K → A: Complete loss of transcriptional activity; when associated with A-507. Ref.29
Mutagenesis3571K → A: Increased transcriptional activity. No effect on protein degradation. Ref.13
Mutagenesis3611L → F: Small reduction in transcriptional activity. No protein degradation. Ref.13
Mutagenesis3641V → G: Greatly reduced transcriptional activity. Protects from protein degradation. Ref.13
Mutagenesis3711A → Q: Almost total loss of transcriptional activity. Ref.28
Mutagenesis3991F → W: Slight loss of transcriptional activity. Ref.28
Mutagenesis4411K → R: No effect on sumoylation. Ref.21
Mutagenesis4841H → W: Almost total loss of transcriptional activity. Ref.28
Mutagenesis5071Y → A: Complete loss of transcriptional activity; when associated with A-339. Ref.28
Mutagenesis5071Y → F: About 40% loss of transcriptional activity. Ref.28
Mutagenesis5091E → K: Abolishes transcriptional activity. Protects from protein degradation. Ref.13 Ref.29
Mutagenesis510 – 5112LF → AA: Decreases interaction with NCOA2.
Sequence conflict3681M → V in AAA02963. Ref.2
Sequence conflict4661I → M in AAA02963. Ref.2
Isoform 4:
Sequence conflict71A → E in AAA02963. Ref.2

Secondary structure

.................................. 523
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha-1) [UniParc].

Last modified April 16, 2014. Version 2.
Checksum: 0FA43BBCE6E28DC7

FASTA52358,975
        10         20         30         40         50         60 
MESAPAAPDP AASEPGSSGA DAAAGSRETP LNQESARKSE PPAPVRRQSY SSTSRGISVT 

        70         80         90        100        110        120 
KKTHTSQIEI IPCKICGDKS SGIHYGVITC EGCKGFFRRS QQSNATYSCP RQKNCLIDRT 

       130        140        150        160        170        180 
SRNRCQHCRL QKCLAVGMSR DAVKFGRMSK KQRDSLYAEV QKHRMQQQQR DHQQQPGEAE 

       190        200        210        220        230        240 
PLTPTYNISA NGLTELHDDL SNYIDGHTPE GSKADSAVSS FYLDIQPSPD QSGLDINGIK 

       250        260        270        280        290        300 
PEPICDYTPA SGFFPYCSFT NGETSPTVSM AELEHLAQNI SKSHLETCQY LREELQQITW 

       310        320        330        340        350        360 
QTFLQEEIEN YQNKQREVMW QLCAIKITEA IQYVVEFAKR IDGFMELCQN DQIVLLKAGS 

       370        380        390        400        410        420 
LEVVFIRMCR AFDSQNNTVY FDGKYASPDV FKSLGCEDFI SFVFEFGKSL CSMHLTEDEI 

       430        440        450        460        470        480 
ALFSAFVLMS ADRSWLQEKV KIEKLQQKIQ LALQHVLQKN HREDGILTKL ICKVSTLRAL 

       490        500        510        520 
CGRHTEKLMA FKAIYPDIVR LHFPPLYKEL FTSEFEPAMQ IDG 

« Hide

Isoform 2 (Alpha-2) [UniParc].

Checksum: 0D9797A147CEE8AE
Show »

FASTA55663,036
Isoform 3 (Alpha-3) [UniParc].

Checksum: 89FEA2A06D25D971
Show »

FASTA54061,108
Isoform 4 (Alpha-4) [UniParc].

Checksum: FD577090E6261B16
Show »

FASTA46853,556

References

« Hide 'large scale' references
[1]"Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors."
Giguere V., Tini M., Flock G., Ong E., Evans R.M., Otulakowski G.
Genes Dev. 8:538-553(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION AS TRANSCRIPTION ACTIVATOR, DNA-BINDING, SUBUNIT.
Tissue: Retina and Testis.
[2]"Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences."
Becker-Andre M., Andre E., Delamarter J.F.
Biochem. Biophys. Res. Commun. 194:1371-1379(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY.
Tissue: Umbilical vein endothelial cell.
[3]"Isolation of cDNA coding for multiple human nuclear receptor clones."
Kaighin V.A., Martin A.L., Aronstam R.S.
Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
Tissue: Kidney.
[4]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
Tissue: Muscle.
[7]"Transcriptional activation and repression by RORalpha, an orphan nuclear receptor required for cerebellar development."
Harding H.P., Atkins G.B., Jaffe A.B., Seo W.J., Lazar M.A.
Mol. Endocrinol. 11:1737-1746(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTION ACTIVATOR, INTERACTION WITH NCOR1, DNA-BINDING, SUBUNIT.
[8]"Coactivators for the orphan nuclear receptor RORalpha."
Atkins G.B., Hu X., Guenther M.G., Rachez C., Freedman L.P., Lazar M.A.
Mol. Endocrinol. 13:1550-1557(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTION ACTIVATOR, INTERACTION WITH MED1 AND NCOA2, MUTAGENESIS OF VAL-335 AND 510-LEU-PHE-511.
[9]"Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD."
Lau P., Bailey P., Dowhan D.H., Muscat G.E.
Nucleic Acids Res. 27:411-420(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MYOGENESIS, INTERACTION WITH EP300.
[10]"Identification of a novel peroxisome proliferator-activated receptor (PPAR) gamma promoter in man and transactivation by the nuclear receptor RORalpha1."
Sundvold H., Lien S.
Biochem. Biophys. Res. Commun. 287:383-390(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTION ACTIVATOR, DNA-BINDING.
[11]"The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response."
Delerive P., Monte D., Dubois G., Trottein F., Fruchart-Najib J., Mariani J., Fruchart J.C., Staels B.
EMBO Rep. 2:42-48(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMATION.
[12]"Transcriptional regulation of apolipoprotein C-III gene expression by the orphan nuclear receptor RORalpha."
Raspe E., Duez H., Gervois P., Fievet C., Fruchart J.C., Besnard S., Mariani J., Tedgui A., Staels B.
J. Biol. Chem. 276:2865-2871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRIGLYCERIDE METABOLISM, DNA-BINDING.
[13]"The co-repressor hairless protects RORalpha orphan nuclear receptor from proteasome-mediated degradation."
Moraitis A.N., Giguere V.
J. Biol. Chem. 278:52511-52518(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTION ACTIVATOR, UBIQUITINATION, MUTAGENESIS OF LYS-357; LEU-361; VAL-364 AND GLU-509.
[14]"Hypoxia-induced activation of the retinoic acid receptor-related orphan receptor alpha4 gene by an interaction between hypoxia-inducible factor-1 and Sp1."
Miki N., Ikuta M., Matsui T.
J. Biol. Chem. 279:15025-15031(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY HYPOXIA (ISOFORM 4).
[15]"Transcriptional regulation of apolipoprotein A5 gene expression by the nuclear receptor RORalpha."
Genoux A., Dehondt H., Helleboid-Chapman A., Duhem C., Hum D.W., Martin G., Pennacchio L.A., Staels B., Fruchart-Najib J., Fruchart J.C.
Arterioscler. Thromb. Vasc. Biol. 25:1186-1192(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRIGLYCERIDE METABOLISM, DNA-BINDING.
[16]"Identification of the human ApoAV gene as a novel RORalpha target gene."
Lind U., Nilsson T., McPheat J., Stroemstedt P.E., Bamberg K., Balendran C., Kang D.
Biochem. Biophys. Res. Commun. 330:233-241(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRIGLYCERIDE METABOLISM, DNA-BINDING.
[17]"RORA, a large common fragile site gene, is involved in cellular stress response."
Zhu Y., McAvoy S., Kuhn R., Smith D.I.
Oncogene 25:2901-2908(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL GROWTH, INDUCTION BY CELLULAR STRESS.
[18]"Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro."
Lechtken A., Hoernig M., Werz O., Corvey N., Zoendorf I., Dingermann T., Brandes R., Steinhilber D.
Biochem. Biophys. Res. Commun. 358:890-896(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, FUNCTION, MUTAGENESIS OF THR-183.
[19]"Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling."
Kim E.J., Yoo Y.G., Yang W.K., Lim Y.S., Na T.Y., Lee I.K., Lee M.O.
Arterioscler. Thromb. Vasc. Biol. 28:1796-1802(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HYPOXIA SIGNALING, INTERACTION WITH HIF1A, INDUCTION BY HYPOXIA, SUBCELLULAR LOCATION.
[20]"Phosphorylation and transcriptional activity regulation of retinoid-related orphan receptor alpha 1 by protein kinases C."
Duplus E., Gras C., Soubeyre V., Vodjdani G., Lemaigre-Dubreuil Y., Brugg B.
J. Neurochem. 104:1321-1332(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTION ACTIVATOR, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[21]"SUMOylation of RORalpha potentiates transcriptional activation function."
Hwang E.J., Lee J.M., Jeong J., Park J.H., Yang Y., Lim J.S., Kim J.H., Baek S.H., Kim K.I.
Biochem. Biophys. Res. Commun. 378:513-517(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-240, MUTAGENESIS OF LYS-240 AND LYS-441.
[22]"Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism."
Jetten A.M.
Nucl. Recept. Signal. 7:3-35(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[23]"Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands."
Wang Y., Kumar N., Solt L.A., Richardson T.I., Helvering L.M., Crumbley C., Garcia-Ordonez R.D., Stayrook K.R., Zhang X., Novick S., Chalmers M.J., Griffin P.R., Burris T.P.
J. Biol. Chem. 285:5013-5025(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN GLUCOSE METABOLISM REGULATION, IDENTIFICATION OF LIGANDS.
[24]"Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand."
Solt L.A., Kumar N., Nuhant P., Wang Y., Lauer J.L., Liu J., Istrate M.A., Kamenecka T.M., Roush W.R., Vidovic D., Schuerer S.C., Xu J., Wagoner G., Drew P.D., Griffin P.R., Burris T.P.
Nature 472:491-494(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN T(H)17 CELLS DIFFERENTIATION, IDENTIFICATION OF LIGANDS.
[25]"EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex."
Lee J.M., Lee J.S., Kim H., Kim K., Park H., Kim J.Y., Lee S.H., Kim I.S., Kim J., Lee M., Chung C.H., Seo S.B., Yoon J.B., Ko E., Noh D.Y., Kim K.I., Kim K.K., Baek S.H.
Mol. Cell 48:572-586(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT LYS-38.
[26]"Action of RORs and their ligands in (patho)physiology."
Solt L.A., Burris T.P.
Trends Endocrinol. Metab. 23:619-627(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION AND LIGANDS.
[27]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-18 (ISOFORM 2).
[28]"X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha."
Kallen J.A., Schlaeppi J.-M., Bitsch F., Geisse S., Geiser M., Delhon I., Fournier B.
Structure 10:1697-1707(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 271-523 IN COMPLEX WITH CHOLESTEROL, FUNCTION AS TRANSCRIPTION ACTIVATOR, IDENTIFICATION OF LIGANDS, MUTAGENESIS OF CYS-323; ALA-330; ALA-371; PHE-399; HIS-484 AND TYR-507, IDENTIFICATION BY MASS SPECTROMETRY.
[29]"Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A."
Kallen J., Schlaeppi J.-M., Bitsch F., Delhon I., Fournier B.
J. Biol. Chem. 279:14033-14038(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 271-523 IN COMPLEX WITH CHOLESTEROL SULFATE, MUTAGENESIS OF CYS-288; CYS-323; ALA-330; LYS-339 AND GLU-509, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U04897 mRNA. Translation: AAA62658.1.
U04898 mRNA. Translation: AAA62659.1.
U04899 mRNA. Translation: AAA62660.1.
L14611 mRNA. Translation: AAA02963.1.
HQ692818 mRNA. Translation: ADZ17329.1.
AC009560 Genomic DNA. No translation available.
AC012404 Genomic DNA. No translation available.
AC022898 Genomic DNA. No translation available.
AC079068 Genomic DNA. No translation available.
AC087385 Genomic DNA. No translation available.
AC107241 Genomic DNA. No translation available.
AC107905 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77594.1.
BC008831 mRNA. Translation: AAH08831.1.
BC100987 mRNA. Translation: AAI00988.1.
BC100988 mRNA. Translation: AAI00989.1.
BC100989 mRNA. Translation: AAI00990.1.
BC100990 mRNA. Translation: AAI00991.1.
PIRA53196.
A56856.
B53196.
C53196.
RefSeqNP_002934.1. NM_002943.3.
NP_599022.1. NM_134260.2.
NP_599023.1. NM_134261.2.
NP_599024.1. NM_134262.2.
UniGeneHs.560343.
Hs.655155.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1N83X-ray1.63A271-523[»]
1S0XX-ray2.20A271-523[»]
ProteinModelPortalP35398.
SMRP35398. Positions 103-545.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112022. 23 interactions.
DIPDIP-29938N.
IntActP35398. 5 interactions.
MINTMINT-2855668.
STRING9606.ENSP00000261523.

Chemistry

BindingDBP35398.
ChEMBLCHEMBL5868.
GuidetoPHARMACOLOGY598.

PTM databases

PhosphoSiteP35398.

Polymorphism databases

DMDM548814.

Proteomic databases

PaxDbP35398.
PRIDEP35398.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261523; ENSP00000261523; ENSG00000069667. [P35398-1]
ENST00000309157; ENSP00000309753; ENSG00000069667. [P35398-3]
ENST00000335670; ENSP00000335087; ENSG00000069667. [P35398-2]
ENST00000449337; ENSP00000402971; ENSG00000069667. [P35398-4]
GeneID6095.
KEGGhsa:6095.
UCSCuc002agt.4. human. [P35398-4]
uc002agv.3. human. [P35398-1]
uc002agw.3. human. [P35398-3]
uc002agx.3. human. [P35398-2]

Organism-specific databases

CTD6095.
GeneCardsGC15M060780.
HGNCHGNC:10258. RORA.
HPACAB009861.
MIM600825. gene.
neXtProtNX_P35398.
PharmGKBPA34630.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324222.
HOGENOMHOG000010200.
HOVERGENHBG106848.
InParanoidP35398.
KOK08532.
OMAGHCLTGQ.
OrthoDBEOG79PJNW.
PhylomeDBP35398.
TreeFamTF319910.

Enzyme and pathway databases

ReactomeREACT_24941. Circadian Clock.
REACT_71. Gene Expression.
SignaLinkP35398.

Gene expression databases

ArrayExpressP35398.
BgeeP35398.
CleanExHS_RORA.
GenevestigatorP35398.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003079. ROR_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01293. RORNUCRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRORA. human.
EvolutionaryTraceP35398.
GeneWikiRAR-related_orphan_receptor_alpha.
GenomeRNAi6095.
NextBio23703.
PROP35398.
SOURCESearch...

Entry information

Entry nameRORA_HUMAN
AccessionPrimary (citable) accession number: P35398
Secondary accession number(s): P35397 expand/collapse secondary AC list , P35399, P45445, Q495X4, Q96H83
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: April 16, 2014
Last modified: April 16, 2014
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM