P35398 (RORA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor ROR-alpha

Alternative name(s):
Nuclear receptor RZR-alpha
Nuclear receptor subfamily 1 group F member 1
Retinoid-related orphan receptor-alpha

Gene names

Name:	RORA
Synonyms:	NR1F1, RZRA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	556 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Orphan nuclear receptor. Binds DNA as a monomer to hormone response elements (HRE) containing a single core motif half-site preceded by a short A-T-rich sequence. This isomer binds to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'. Regulates a number of genes involved in lipid metabolism such as apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in cerebellum and photoreceptor development including PCP2, OPN1SW, OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal muscle development with MYOD1. Possible receptor for cholesterol or one of its derivatives. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.19
Enzyme regulation	Activated by CaMK4. Ref.10
Subunit structure	Monomer. Interacts (via the DNA-binding domain) with HIF1; the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Ref.15
Subcellular location	Nucleus Ref.16.
Tissue specificity	Widely expressed in a number of tissues. Ref.2
Induction	By hypoxia and melatonin. Ref.10 Ref.15
Post-translational modification	Phosphorylation by PKC in neurons inhibits transcriptional activity. Phosphorylated on Thr-216 by ERK2 in vitro. Ref.14 Ref.16 Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2, PIAS3, PIASy but not PIAS1, enhances the transcriptional activity. Desumoylated by SENP1. Ref.17 Ubiquitinated. Ubiquitination is required for efficient transcriptional activity and is prevented by Hairless. Ref.11
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cGMP metabolic process Inferred from electronic annotation. Source: Compara cerebellar Purkinje cell differentiation Inferred from electronic annotation. Source: Compara nitric oxide biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17545671. Source: MGI regulation of macrophage activation Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement Ref.1. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NR0B1	P51843	2	EBI-748689,EBI-946109

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-2 (identifier: P35398-1)

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 Alpha-1 (identifier: P35398-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: MNEGAPGDSD...KEVQTGYMNA → MESAPAAPDP...ISVTKKTHTS

Isoform Alpha-3 (identifier: P35398-3)

The sequence of this isoform differs from the canonical sequence as follows:
     46-98: RDELFGILQI...DKEVQTGYMN → SSSTCSSLSR...FSFLLPALRK

Isoform Alpha-4 (identifier: P35398-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MNEGAPGDSD...DKEVQTGYMN → MMYFVIAAMK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 556

556

Nuclear receptor ROR-alpha

PRO_0000053512

Regions

DNA binding

106 – 171

66

Nuclear receptor

Zinc finger

106 – 126

21

NR C4-type

Zinc finger

142 – 166

25

NR C4-type

Region

1 – 105

105

Modulating

Region

172 – 304

133

Hinge

Region

305 – 556

252

Ligand-binding

Compositional bias

199 – 202

4

Poly-Gln

Amino acid modifications

Cross-link

273

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.17

Natural variations

Alternative sequence

1 – 99

99

MNEGA…GYMNA → MESAPAAPDPAASEPGSSGA DAAAGSRETPLNQESARKSE PPAPVRRQSYSSTSRGISVT KKTHTS in isoform Alpha-1.

VSP_003655

Alternative sequence

1 – 98

98

MNEGA…TGYMN → MMYFVIAAMK in isoform Alpha-4.

VSP_003657

Alternative sequence

46 – 98

53

RDELF…TGYMN → SSSTCSSLSRLFWSQLEHIN WDGATAKNFINLREFFSFLL PALRK in isoform Alpha-3.

VSP_003656

Natural variant

18

1

P → S in a colorectal cancer sample; somatic mutation. Ref.18

VAR_036062

Experimental info

Mutagenesis

216

1

T → A: Greatly increased transcriptional activity. Decrease in repression by RevErbalpha. Ref.14

Mutagenesis

216

1

T → D or E: Some increase in transcriptional activity. No change in repression by RevErbalpha. Ref.14

Mutagenesis

216

1

T → R: Attenuates transcriptional activity. Ref.14

Mutagenesis

216

1

T → V or I: Some increase in transcriptional activity. Ref.14

Mutagenesis

273

1

K → R: Loss of sumoylation. Ref.17

Mutagenesis

321

1

C → Q: Less effect on transcriptional activity with cholesterol sulfate as substrate as compared to cholesterol as substrate. Ref.20

Mutagenesis

356

1

C → L: About 60% loss of transcriptional activity. Ref.19 Ref.20

Mutagenesis

363

1

A → L: About 80% loss of transcriptional activity. Ref.19 Ref.20

Mutagenesis

372

1

K → A: Complete loss of transcriptional activity; when associated with A-540. Ref.20

Mutagenesis

390

1

K → A: Increased transcriptional activity. No effect on protein degradation. Ref.11

Mutagenesis

394

1

L → F: Small reduction in transcriptional activity. No protein degradation. Ref.11

Mutagenesis

397

1

V → G: Greatly reduced transcriptional activity. Greater protein levels. Ref.11

Mutagenesis

404

1

A → Q: Almost total loss of transcriptional activity. Ref.19

Mutagenesis

432

1

F → W: Slight loss of transcriptional activity. Ref.19

Mutagenesis

474

1

K → R: No effect on sumoylation. Ref.17

Mutagenesis

517

1

H → W: Almost total loss of transcriptional activity. Ref.19

Mutagenesis

540

1

Y → A: Complete loss of transcriptional activity; when associated with A-372. Ref.19

Mutagenesis

540

1

Y → F: About 40% loss of transcriptional activity. Ref.19

Mutagenesis

542

1

E → K: Abolishes transcriptional activity. Ref.11 Ref.20

Sequence conflict

401

1

M → V in AAA02963. Ref.2

Sequence conflict

499

1

I → M in AAA02963. Ref.2

Isoform Alpha-4:

Sequence conflict

8

1

A → E in AAA02963. Ref.2

Secondary structure

1

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556

Helix Strand Turn

Details...

Helix

304 – 319

16

Helix

325 – 330

6

Turn

331 – 333

3

Helix

338 – 346

9

Helix

349 – 373

25

Turn

375 – 379

5

Helix

382 – 400

19

Helix

401 – 404

4

Turn

407 – 410

4

Beta strand

411 – 414

4

Beta strand

417 – 419

3

Helix

421 – 427

7

Helix

430 – 444

15

Helix

450 – 461

12

Helix

472 – 493

22

Helix

499 – 527

29

Helix

529 – 535

7

Helix

538 – 543

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-2 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 0D9797A147CEE8AE	FASTA	556	63,036
	10 20 30 40 50 60 MNEGAPGDSD LETEARVPWS IMGHCLRTGQ ARMSATPTPA GEGARRDELF GILQILHQCI 70 80 90 100 110 120 LSSGDAFVLT GVCCSWRQNG KPPYSQKEDK EVQTGYMNAQ IEIIPCKICG DKSSGIHYGV 130 140 150 160 170 180 ITCEGCKGFF RRSQQSNATY SCPRQKNCLI DRTSRNRCQH CRLQKCLAVG MSRDAVKFGR 190 200 210 220 230 240 MSKKQRDSLY AEVQKHRMQQ QQRDHQQQPG EAEPLTPTYN ISANGLTELH DDLSNYIDGH 250 260 270 280 290 300 TPEGSKADSA VSSFYLDIQP SPDQSGLDIN GIKPEPICDY TPASGFFPYC SFTNGETSPT 310 320 330 340 350 360 VSMAELEHLA QNISKSHLET CQYLREELQQ ITWQTFLQEE IENYQNKQRE VMWQLCAIKI 370 380 390 400 410 420 TEAIQYVVEF AKRIDGFMEL CQNDQIVLLK AGSLEVVFIR MCRAFDSQNN TVYFDGKYAS 430 440 450 460 470 480 PDVFKSLGCE DFISFVFEFG KSLCSMHLTE DEIALFSAFV LMSADRSWLQ EKVKIEKLQQ 490 500 510 520 530 540 KIQLALQHVL QKNHREDGIL TKLICKVSTL RALCGRHTEK LMAFKAIYPD IVRLHFPPLY 550 KELFTSEFEP AMQIDG
	Isoform Alpha-1 [UniParc]. Checksum: 0FA43BBCE6E28DC7	FASTA	523	58,975
	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
	Isoform Alpha-3 [UniParc]. Checksum: 505F1369DEFEB3A6	FASTA	548	62,251
	10 20 30 40 50 60 MNEGAPGDSD LETEARVPWS IMGHCLRTGQ ARMSATPTPA GEGARSSSTC SSLSRLFWSQ 70 80 90 100 110 120 LEHINWDGAT AKNFINLREF FSFLLPALRK AQIEIIPCKI CGDKSSGIHY GVITCEGCKG 130 140 150 160 170 180 FFRRSQQSNA TYSCPRQKNC LIDRTSRNRC QHCRLQKCLA VGMSRDAVKF GRMSKKQRDS 190 200 210 220 230 240 LYAEVQKHRM QQQQRDHQQQ PGEAEPLTPT YNISANGLTE LHDDLSNYID GHTPEGSKAD 250 260 270 280 290 300 SAVSSFYLDI QPSPDQSGLD INGIKPEPIC DYTPASGFFP YCSFTNGETS PTVSMAELEH 310 320 330 340 350 360 LAQNISKSHL ETCQYLREEL QQITWQTFLQ EEIENYQNKQ REVMWQLCAI KITEAIQYVV 370 380 390 400 410 420 EFAKRIDGFM ELCQNDQIVL LKAGSLEVVF IRMCRAFDSQ NNTVYFDGKY ASPDVFKSLG 430 440 450 460 470 480 CEDFISFVFE FGKSLCSMHL TEDEIALFSA FVLMSADRSW LQEKVKIEKL QQKIQLALQH 490 500 510 520 530 540 VLQKNHREDG ILTKLICKVS TLRALCGRHT EKLMAFKAIY PDIVRLHFPP LYKELFTSEF EPAMQIDG
	Isoform Alpha-4 [UniParc]. Checksum: 906C317B11AB3C2D	FASTA	468	53,540
	10 20 30 40 50 60 MMYFVIAAMK AQIEIIPCKI CGDKSSGIHY GVITCEGCKG FFRRSQQSNA TYSCPRQKNC 70 80 90 100 110 120 LIDRTSRNRC QHCRLQKCLA VGMSRDAVKF GRMSKKQRDS LYAEVQKHRM QQQQRDHQQQ 130 140 150 160 170 180 PGEAEPLTPT YNISANGLTE LHDDLSNYID GHTPEGSKAD SAVSSFYLDI QPSPDQSGLD 190 200 210 220 230 240 INGIKPEPIC DYTPASGFFP YCSFTNGETS PTVSMAELEH LAQNISKSHL ETCQYLREEL 250 260 270 280 290 300 QQITWQTFLQ EEIENYQNKQ REVMWQLCAI KITEAIQYVV EFAKRIDGFM ELCQNDQIVL 310 320 330 340 350 360 LKAGSLEVVF IRMCRAFDSQ NNTVYFDGKY ASPDVFKSLG CEDFISFVFE FGKSLCSMHL 370 380 390 400 410 420 TEDEIALFSA FVLMSADRSW LQEKVKIEKL QQKIQLALQH VLQKNHREDG ILTKLICKVS 430 440 450 460 TLRALCGRHT EKLMAFKAIY PDIVRLHFPP LYKELFTSEF EPAMQIDG

References

	« Hide 'large scale' referencesShow '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 ALPHA-1; ALPHA-2 AND ALPHA-3). 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 ALPHA-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 ALPHA-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. , 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. , 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 ALPHA-1 AND ALPHA-4). Tissue: Muscle.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes." Jetten A.M., Kurebayashi S., Ueda E. Prog. Nucleic Acid Res. Mol. Biol. 69:205-247(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[11]	"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: UBIQUITINATION, FUNCTION, MUTAGENESIS OF LYS-390; LEU-394; VAL-397 AND GLU-542.
[12]	"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.
[13]	"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.
[14]	"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-216.
[15]	"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: INTERACTION WITH HIF1A, FUNCTION, INDUCTION.
[16]	"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: PHOSPHORYLATION, SUBCELLULAR LOCATION, FUNCTION.
[17]	"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-273, MUTAGENESIS OF LYS-273 AND LYS-474.
[18]	"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. , 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.
[19]	"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 304-556 IN COMPLEX WITH CHOLESTEROL, POSSIBLE FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF CYS-356; ALA-363; ALA-404; PHE-432; HIS-517 AND TYR-540.
[20]	"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 304-556 IN COMPLEX WITH CHOLESTEROL SULFATE, MASS SPECTROMETRY, MUTAGENESIS OF CYS-321; CYS-356; ALA-363; LYS-372 AND GLU-542.
+	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.

IPI

IPI00018225.
IPI00107635.
IPI00218544.
IPI00243584.

PIR

A53196.
A56856.
B53196.
C53196.

RefSeq

NP_002934.1. NM_002943.3.
NP_599022.1. NM_134260.2.
NP_599023.1. NM_134261.2.
NP_599024.1. NM_134262.2.

UniGene

Hs.560343.
Hs.655155.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N83	X-ray	1.63	A	304-556	[»]
1S0X	X-ray	2.20	A	304-556	[»]

ProteinModelPortal

P35398.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29938N.

IntAct

P35398. 5 interactions.

MINT

MINT-2855668.

STRING

9606.ENSP00000261523.

PTM databases

PhosphoSite

P35398.

Polymorphism databases

DMDM

548814.

Proteomic databases

PaxDb

P35398.

PRIDE

P35398.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261523; ENSP00000261523; ENSG00000069667.
ENST00000309157; ENSP00000309753; ENSG00000069667.
ENST00000335670; ENSP00000335087; ENSG00000069667.
ENST00000449337; ENSP00000402971; ENSG00000069667.

GeneID

6095.

KEGG

hsa:6095.

UCSC

uc002agt.4. human.
uc002agv.3. human.
uc002agw.3. human.
uc002agx.3. human.

Organism-specific databases

CTD

6095.

GeneCards

GC15M060780.

HGNC

HGNC:10258. RORA.

HPA

CAB009861.

MIM

600825. gene.

neXtProt

NX_P35398.

PharmGKB

PA34630.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG324222.

HOGENOM

HOG000010200.

HOVERGEN

HBG106848.

InParanoid

P35398.

KO

K08532.

OMA

VAAQIEI.

PhylomeDB

P35398.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_24941. Circadian Clock.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P35398.

Bgee

P35398.

CleanEx

HS_RORA.

Genevestigator

P35398.

GermOnline

ENSG00000069667. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR008946. 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]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR01293. RORNUCRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P35398.

ChEMBL

CHEMBL5868.

ChiTaRS

RORA. human.

EvolutionaryTrace

P35398.

GenomeRNAi

6095.

NextBio

23703.

SOURCE

Search...

Entry information

Entry name

RORA_HUMAN

Accession

Primary (citable) accession number: P35398
Secondary accession number(s): P35397 , P35399, P45445, Q495X4, Q96H83

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 1, 2013
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.