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UniProtKB - P51448 (RORA_MOUSE)

Protein

Nuclear receptor ROR-alpha

Gene

Rora

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.15 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi73 – 138Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri73 – 93NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri109 – 133NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, DNA-binding, Receptor
Biological processBiological rhythms, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Rora
Synonyms:Nr1f1, Rzra
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:104661 Rora

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Rora are the cause of the staggerer (SG) mutant phenotype which is characterized by disturbance of Purkinje cell development and immune system functioning. This phenotype exhibits lower body weight, reduced adiposity, decreased plasma cholesterol, triglyceride and apolipoprotein CIII levels, and is resistant to diet-induced obesity. Also has abnormal circadian rhythms.8 Publications

Keywords - Diseasei

Disease mutation

Chemistry databases

ChEMBLiCHEMBL3217403

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535131 – 523Nuclear receptor ROR-alphaAdd BLAST523

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38N6-methyllysineBy similarity1
Modified residuei183Phosphothreonine; by MAPK1By similarity1
Cross-linki240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylation by conventional PKCs in neurons inhibits transcriptional activity. Phosphorylated on Thr-183 by MAPK1/ERK1 in vitro.By similarity
Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2, PIAS3, PIAS4 but not PIAS1, enhances the transcriptional activity. Desumoylated by SENP1.By similarity
Ubiquitinated, leading to its degradation by the proteasome. Proteasomal degradation is required for efficient transcriptional activity and is prevented by HR.By similarity
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.By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP51448
PeptideAtlasiP51448
PRIDEiP51448

PTM databases

iPTMnetiP51448
PhosphoSitePlusiP51448

Expressioni

Tissue specificityi

Expressed in cerebellum, heart, liver, lung, kidney, retina and brown and white adipose tissues. Expressed in the subset of mature Th17 cells.4 Publications

Developmental stagei

In cerebellum, expression begins at E12.5. In the developing retina, first expressed at E17 in the ganglion cell layer. At P3, expressed in the inner border of the neuroblasitic border (presumptive amacrine cells). By P6, levels increase in developing cones. Expression found in the presumptive bipolar cells by P9. During adipocyte differentiation, expression gradually increases.3 Publications

Inductioni

In T(H) cells, induced upon antigen receptor ligation in the presence of IL6 and TGB1 (via STAT3). Oscillates diurnally in central nervous system. In liver, Isoform 1 oscillates diurnally but not isoform 4.4 Publications

Gene expression databases

BgeeiENSMUSG00000032238 Expressed in 335 organ(s), highest expression level in medial geniculate body
CleanExiMM_RORA
ExpressionAtlasiP51448 baseline and differential
GenevisibleiP51448 MM

Interactioni

Subunit structurei

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. Interacts with NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3 (via LXXLL motif) (By similarity).By similarity10 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi202956, 1 interactor
DIPiDIP-35351N
IntActiP51448, 3 interactors
MINTiP51448
STRINGi10090.ENSMUSP00000034766

Structurei

3D structure databases

ProteinModelPortaliP51448
SMRiP51448
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini272 – 510NR LBDPROSITE-ProRule annotationAdd BLAST239

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni139 – 271HingeAdd BLAST133

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi506 – 511AF-26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi101 – 175Gln-richAdd BLAST75

Domaini

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

Sequence similaritiesi

Belongs to the nuclear hormone receptor family. NR1 subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri73 – 93NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri109 – 133NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4216 Eukaryota
ENOG410XUGR LUCA
GeneTreeiENSGT00870000136388
HOGENOMiHOG000010200
HOVERGENiHBG106848
InParanoidiP51448
KOiK08532
OMAiYQNKPRE
OrthoDBiEOG091G0649
PhylomeDBiP51448
TreeFamiTF319910

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR003079 ROR_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01293 RORNUCRECPTR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative promoter usage. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P51448-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MESAPAAPDP AASEPGSSGS EAAAGSRETP LTQDTGRKSE APGAGRRQSY 
        60         70         80         90        100
ASSSRGISVT KKTHTSQIEI IPCKICGDKS SGIHYGVITC EGCKGFFRRS 
       110        120        130        140        150
QQSNATYSCP RQKNCLIDRT SRNRCQHCRL QKCLAVGMSR DAVKFGRMSK 
       160        170        180        190        200
KQRDSLYAEV QKHRMQQQQR DHQQQPGEAE PLTPTYNISA NGLTELHDDL 
       210        220        230        240        250
STYMDGHTPE GSKADSAVSS FYLDIQPSPD QSGLDINGIK PEPICDYTPA 
       260        270        280        290        300
SGFFPYCSFT NGETSPTVSM AELEHLAQNI SKSHLETCQY LREELQQITW 
       310        320        330        340        350
QTFLQEEIEN YQNKQREVMW QLCAIKITEA IQYVVEFAKR IDGFMELCQN 
       360        370        380        390        400
DQIVLLKAGS LEVVFIRMCR AFDSQNNTVY FDGKYASPDV FKSLGCEDFI 
       410        420        430        440        450
SFVFEFGKSL CSMHLTEDEI ALFSAFVLMS ADRSWLQEKV KIEKLQQKIQ 
       460        470        480        490        500
LALQHVLQKN HREDGILTKL ICKVSTLRAL CGRHTEKLMA FKAIYPDIVR 
       510        520 
LHFPPLYKEL FTSEFEPAMQ IDG
Length:523
Mass (Da):58,845
Last modified:October 1, 1996 - v1
Checksum:iA194E02E4D9D177E
GO
Isoform 2 (identifier: P51448-3)
Also known as: Alpha-2
Sequence is not available
Length:–
Mass (Da):–
Isoform 3 (identifier: P51448-4)
Also known as: Alpha-3
Sequence is not available
Length:–
Mass (Da):–
Isoform 4 (identifier: P51448-2) [UniParc]FASTAAdd to basket
Also known as: Alpha-4

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: MESAPAAPDP...ISVTKKTHTS → MYFVIAAMKA

Show »
Length:467
Mass (Da):53,414
Checksum:i5621E275EC282A54
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3UZ02G3UZ02_MOUSE
Nuclear receptor ROR-alpha
Rora
62Annotation score:

Sequence cautioni

The sequence AAH03757 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA69930 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti163H → R in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti180 – 181EP → T in CAA69930 (PubMed:7935491).Curated2
Sequence conflicti182L → I in AAB46801 (PubMed:8750880).Curated1
Sequence conflicti182L → I in BAA22970 (PubMed:8750880).Curated1
Sequence conflicti193 – 194LT → SA in CAA69930 (PubMed:7935491).Curated2
Sequence conflicti304L → W in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti315Missing in AAB46801 (PubMed:8750880).Curated1
Sequence conflicti315Missing in BAA22970 (PubMed:8750880).Curated1
Sequence conflicti362E → G in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti433R → P in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti450 – 451QL → HM in CAA69930 (PubMed:7935491).Curated2
Sequence conflicti487K → N in AAB46801 (PubMed:8750880).Curated1
Sequence conflicti487K → N in BAA22970 (PubMed:8750880).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti275 – 314Missing in SG; disturbance of Purkinje cell and muscle development, lipid metabolism, circadian behavior and immune system functioning. 1 PublicationAdd BLAST40

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0036581 – 66MESAP…KTHTS → MYFVIAAMKA in isoform 4. 4 PublicationsAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53228 mRNA Translation: AAC52513.1
Y08640 mRNA Translation: CAA69930.1 Different initiation.
Z82994 mRNA Translation: CAB05396.1
S82720 mRNA Translation: AAB46801.2
D45910 mRNA Translation: BAA22970.1
BC003757 mRNA Translation: AAH03757.2 Different initiation.
CCDSiCCDS23314.1 [P51448-1]
CCDS72268.1 [P51448-2]
PIRiS68517
RefSeqiNP_001276845.1, NM_001289916.1 [P51448-2]
NP_038674.1, NM_013646.2 [P51448-1]
UniGeneiMm.378450
Mm.391890
Mm.427266
Mm.445802
Mm.491288

Genome annotation databases

EnsembliENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238 [P51448-1]
ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238 [P51448-2]
GeneIDi19883
KEGGimmu:19883
UCSCiuc009qmx.2 mouse [P51448-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53228 mRNA Translation: AAC52513.1
Y08640 mRNA Translation: CAA69930.1 Different initiation.
Z82994 mRNA Translation: CAB05396.1
S82720 mRNA Translation: AAB46801.2
D45910 mRNA Translation: BAA22970.1
BC003757 mRNA Translation: AAH03757.2 Different initiation.
CCDSiCCDS23314.1 [P51448-1]
CCDS72268.1 [P51448-2]
PIRiS68517
RefSeqiNP_001276845.1, NM_001289916.1 [P51448-2]
NP_038674.1, NM_013646.2 [P51448-1]
UniGeneiMm.378450
Mm.391890
Mm.427266
Mm.445802
Mm.491288

3D structure databases

ProteinModelPortaliP51448
SMRiP51448
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202956, 1 interactor
DIPiDIP-35351N
IntActiP51448, 3 interactors
MINTiP51448
STRINGi10090.ENSMUSP00000034766

Chemistry databases

ChEMBLiCHEMBL3217403

PTM databases

iPTMnetiP51448
PhosphoSitePlusiP51448

Proteomic databases

PaxDbiP51448
PeptideAtlasiP51448
PRIDEiP51448

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238 [P51448-1]
ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238 [P51448-2]
GeneIDi19883
KEGGimmu:19883
UCSCiuc009qmx.2 mouse [P51448-1]

Organism-specific databases

CTDi6095
MGIiMGI:104661 Rora

Phylogenomic databases

eggNOGiKOG4216 Eukaryota
ENOG410XUGR LUCA
GeneTreeiENSGT00870000136388
HOGENOMiHOG000010200
HOVERGENiHBG106848
InParanoidiP51448
KOiK08532
OMAiYQNKPRE
OrthoDBiEOG091G0649
PhylomeDBiP51448
TreeFamiTF319910

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors

Miscellaneous databases

ChiTaRSiRora mouse
PROiPR:P51448
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032238 Expressed in 335 organ(s), highest expression level in medial geniculate body
CleanExiMM_RORA
ExpressionAtlasiP51448 baseline and differential
GenevisibleiP51448 MM

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR003079 ROR_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01293 RORNUCRECPTR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRORA_MOUSE
AccessioniPrimary (citable) accession number: P51448
Secondary accession number(s): P70283
, P97741, P97773, Q923G1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 182 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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