UniProtKB - P51448 (RORA_MOUSE)
Nuclear receptor ROR-alpha
Rora
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 G6PC1 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 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 73 – 138 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 66 | |
Zinc fingeri | 73 – 93 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 109 – 133 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- beta-catenin binding Source: UniProtKB
- DNA binding Source: MGI
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- ligand-activated transcription factor activity Source: UniProtKB
- nuclear receptor activity Source: GO_Central
- oxysterol binding Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: MGI
- sequence-specific DNA binding Source: UniProtKB
- transcription coactivator binding Source: UniProtKB
- transcription corepressor binding Source: MGI
- zinc ion binding Source: InterPro
GO - Biological processi
- angiogenesis Source: UniProtKB
- cellular response to hypoxia Source: UniProtKB
- cellular response to interleukin-1 Source: MGI
- cellular response to sterol Source: UniProtKB
- cellular response to tumor necrosis factor Source: MGI
- cerebellar granule cell precursor proliferation Source: UniProtKB
- cerebellar Purkinje cell differentiation Source: MGI
- cGMP metabolic process Source: MGI
- cholesterol homeostasis Source: UniProtKB
- circadian regulation of gene expression Source: UniProtKB
- intracellular receptor signaling pathway Source: UniProtKB
- muscle cell differentiation Source: UniProtKB
- negative regulation of fat cell differentiation Source: GO_Central
- negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- negative regulation of inflammatory response Source: UniProtKB
- nitric oxide biosynthetic process Source: MGI
- positive regulation of circadian rhythm Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of vascular endothelial growth factor production Source: UniProtKB
- regulation of circadian rhythm Source: UniProtKB
- regulation of glucose metabolic process Source: UniProtKB
- regulation of macrophage activation Source: MGI
- regulation of smoothened signaling pathway Source: UniProtKB
- regulation of steroid metabolic process Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- T-helper 17 cell differentiation Source: GO_Central
- triglyceride homeostasis Source: UniProtKB
- xenobiotic metabolic process Source: UniProtKB
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding, Receptor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-383280, Nuclear Receptor transcription pathway R-MMU-4090294, SUMOylation of intracellular receptors |
Names & Taxonomyi
Protein namesi | Recommended name: Nuclear receptor ROR-alphaAlternative 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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104661, Rora |
VEuPathDBi | HostDB:ENSMUSG00000032238 |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation2 Publications
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Keywords - Diseasei
Disease variantChemistry databases
ChEMBLi | CHEMBL3217403 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053513 | 1 – 523 | Nuclear receptor ROR-alphaAdd BLAST | 523 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 38 | N6-methyllysineBy similarity | 1 | |
Modified residuei | 183 | Phosphothreonine; by MAPK1By similarity | 1 | |
Cross-linki | 240 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P51448 |
PeptideAtlasi | P51448 |
PRIDEi | P51448 |
ProteomicsDBi | 260916 [P51448-1] 260917 [P51448-2] |
PTM databases
iPTMneti | P51448 |
PhosphoSitePlusi | P51448 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000032238, Expressed in medial geniculate body and 356 other tissues |
ExpressionAtlasi | P51448, baseline and differential |
Genevisiblei | P51448, 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 PublicationsBinary interactionsi
GO - Molecular functioni
- beta-catenin binding Source: UniProtKB
- transcription coactivator binding Source: UniProtKB
- transcription corepressor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 202956, 1 interactor |
CORUMi | P51448 |
DIPi | DIP-35351N |
IntActi | P51448, 4 interactors |
MINTi | P51448 |
STRINGi | 10090.ENSMUSP00000034766 |
Miscellaneous databases
RNActi | P51448, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 272 – 510 | NR LBDPROSITE-ProRule annotationAdd BLAST | 239 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 63 | DisorderedSequence analysisAdd BLAST | 63 | |
Regioni | 154 – 183 | DisorderedSequence analysisAdd BLAST | 30 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 506 – 511 | AF-2 | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 19 – 36 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 46 – 63 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 154 – 169 | Basic and acidic residuesSequence analysisAdd BLAST | 16 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 73 – 93 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 109 – 133 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG4216, Eukaryota |
GeneTreei | ENSGT00940000157387 |
HOGENOMi | CLU_007368_2_0_1 |
InParanoidi | P51448 |
OMAi | SYIDGHT |
PhylomeDBi | P51448 |
TreeFami | TF319910 |
Family and domain databases
CDDi | cd06968, NR_DBD_ROR, 1 hit |
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR044101, NR_DBD_ROR IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR003079, ROR_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR01293, RORNUCRECPTR PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative promoter usage. AlignAdd to basketThis entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketG3UZ02 | G3UZ02_MOUSE | Nuclear receptor ROR-alpha | Rora | 62 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 163 | H → R in CAA69930 (PubMed:7935491).Curated | 1 | |
Sequence conflicti | 180 – 181 | EP → T in CAA69930 (PubMed:7935491).Curated | 2 | |
Sequence conflicti | 182 | L → I in AAB46801 (PubMed:8750880).Curated | 1 | |
Sequence conflicti | 182 | L → I in BAA22970 (PubMed:8750880).Curated | 1 | |
Sequence conflicti | 193 – 194 | LT → SA in CAA69930 (PubMed:7935491).Curated | 2 | |
Sequence conflicti | 304 | L → W in CAA69930 (PubMed:7935491).Curated | 1 | |
Sequence conflicti | 315 | Missing in AAB46801 (PubMed:8750880).Curated | 1 | |
Sequence conflicti | 315 | Missing in BAA22970 (PubMed:8750880).Curated | 1 | |
Sequence conflicti | 362 | E → G in CAA69930 (PubMed:7935491).Curated | 1 | |
Sequence conflicti | 433 | R → P in CAA69930 (PubMed:7935491).Curated | 1 | |
Sequence conflicti | 450 – 451 | QL → HM in CAA69930 (PubMed:7935491).Curated | 2 | |
Sequence conflicti | 487 | K → N in AAB46801 (PubMed:8750880).Curated | 1 | |
Sequence conflicti | 487 | K → N in BAA22970 (PubMed:8750880).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 275 – 314 | Missing in SG; disturbance of Purkinje cell and muscle development, lipid metabolism, circadian behavior and immune system functioning. 1 PublicationAdd BLAST | 40 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_003658 | 1 – 66 | MESAP…KTHTS → MYFVIAAMKA in isoform 4. 4 PublicationsAdd BLAST | 66 |
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. |
CCDSi | CCDS23314.1 [P51448-1] CCDS72268.1 [P51448-2] |
PIRi | S68517 |
RefSeqi | NP_001276845.1, NM_001289916.1 [P51448-2] NP_038674.1, NM_013646.2 [P51448-1] |
Genome annotation databases
Ensembli | ENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238 [P51448-1] ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238 [P51448-2] |
GeneIDi | 19883 |
KEGGi | mmu:19883 |
UCSCi | uc009qmx.2, mouse [P51448-1] |
Keywords - Coding sequence diversityi
Alternative promoter usageSimilar 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. |
CCDSi | CCDS23314.1 [P51448-1] CCDS72268.1 [P51448-2] |
PIRi | S68517 |
RefSeqi | NP_001276845.1, NM_001289916.1 [P51448-2] NP_038674.1, NM_013646.2 [P51448-1] |
3D structure databases
SMRi | P51448 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 202956, 1 interactor |
CORUMi | P51448 |
DIPi | DIP-35351N |
IntActi | P51448, 4 interactors |
MINTi | P51448 |
STRINGi | 10090.ENSMUSP00000034766 |
Chemistry databases
ChEMBLi | CHEMBL3217403 |
PTM databases
iPTMneti | P51448 |
PhosphoSitePlusi | P51448 |
Proteomic databases
PaxDbi | P51448 |
PeptideAtlasi | P51448 |
PRIDEi | P51448 |
ProteomicsDBi | 260916 [P51448-1] 260917 [P51448-2] |
Protocols and materials databases
Antibodypediai | 4080, 574 antibodies from 37 providers |
DNASUi | 19883 |
Genome annotation databases
Ensembli | ENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238 [P51448-1] ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238 [P51448-2] |
GeneIDi | 19883 |
KEGGi | mmu:19883 |
UCSCi | uc009qmx.2, mouse [P51448-1] |
Organism-specific databases
CTDi | 6095 |
MGIi | MGI:104661, Rora |
VEuPathDBi | HostDB:ENSMUSG00000032238 |
Phylogenomic databases
eggNOGi | KOG4216, Eukaryota |
GeneTreei | ENSGT00940000157387 |
HOGENOMi | CLU_007368_2_0_1 |
InParanoidi | P51448 |
OMAi | SYIDGHT |
PhylomeDBi | P51448 |
TreeFami | TF319910 |
Enzyme and pathway databases
Reactomei | R-MMU-383280, Nuclear Receptor transcription pathway R-MMU-4090294, SUMOylation of intracellular receptors |
Miscellaneous databases
BioGRID-ORCSi | 19883, 0 hits in 65 CRISPR screens |
ChiTaRSi | Rora, mouse |
PROi | PR:P51448 |
RNActi | P51448, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000032238, Expressed in medial geniculate body and 356 other tissues |
ExpressionAtlasi | P51448, baseline and differential |
Genevisiblei | P51448, MM |
Family and domain databases
CDDi | cd06968, NR_DBD_ROR, 1 hit |
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR044101, NR_DBD_ROR IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR003079, ROR_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR01293, RORNUCRECPTR PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RORA_MOUSE | |
Accessioni | P51448Primary (citable) accession number: P51448 Secondary accession number(s): P70283 Q923G1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 201 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families