UniProtKB - P51450 (RORG_MOUSE)
Nuclear receptor ROR-gamma
Rorc
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 cellular differentiation, immunity, peripheral 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 gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts (PubMed:17666523, PubMed:19381306, PubMed:19965867, PubMed:21853531, PubMed:22789990, PubMed:23723244).
Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner (PubMed:22753030).
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 RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock (PubMed:22753030).
Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA 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 SULT1E1 (PubMed:21853531).
Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization.
7 PublicationsEssential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches (PubMed:10602018, PubMed:14691482, PubMed:16148126).
Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for 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 (PubMed:16990136, PubMed:18164222, PubMed:26607793).
May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus (PubMed:9881970, PubMed:10602018, PubMed:14691482, PubMed:16148126, PubMed:16990136, PubMed:18164222).
Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (By similarity).
By similarity7 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 31 – 96 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 66 | |
Zinc fingeri | 31 – 51 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 67 – 91 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: MGI
- ligand-activated transcription factor activity Source: MGI
- nuclear receptor activity Source: GO_Central
- oxysterol binding Source: MGI
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- sequence-specific double-stranded DNA binding Source: MGI
- transcription coactivator binding Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- adipose tissue development Source: UniProtKB
- alpha-beta T cell differentiation Source: MGI
- cell differentiation Source: MGI
- cellular response to sterol Source: MGI
- circadian regulation of gene expression Source: UniProtKB
- lymph node development Source: UniProtKB
- mucosa-associated lymphoid tissue development Source: MGI
- negative regulation of thymocyte apoptotic process Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: MGI
- Peyer's patch development Source: UniProtKB
- positive regulation of circadian rhythm Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- protein phosphorylation Source: MGI
- regulation of fat cell differentiation Source: UniProtKB
- regulation of gamma-delta T cell differentiation Source: MGI
- regulation of glucose metabolic process Source: UniProtKB
- regulation of steroid metabolic process Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- T cell differentiation in thymus Source: MGI
- T-helper 17 cell differentiation Source: MGI
- T-helper cell differentiation 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 [P51450-2] |
Names & Taxonomyi
Protein namesi | Recommended name: Nuclear receptor ROR-gammaAlternative name(s): Nuclear receptor RZR-gamma Nuclear receptor subfamily 1 group F member 3 RAR-related orphan receptor C Retinoid-related orphan receptor-gamma Thymus orphan receptor Short name: TOR |
Gene namesi | Name:Rorc Synonyms:Nr1f3, Rorg, Thor |
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:104856, Rorc |
VEuPathDBi | HostDB:ENSMUSG00000028150 |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation3 Publications
Nucleus
- nuclear body Source: MGI
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Plasma Membrane
- external side of plasma membrane Source: MGI
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 31 | C → A: Loss of adipogenesis inhibition, when associated with A-48. 1 Publication | 1 | |
Mutagenesisi | 48 | C → A: Loss of adipogenesis inhibition, when associated with A-31. 1 Publication | 1 | |
Mutagenesisi | 56 – 57 | RR → AG: Abolishes DNA-binding. No effect neither on interaction with NCOA1 and NCOA2 nor on inhibition of NFATC1 expression. 1 Publication | 2 | |
Mutagenesisi | 500 | Y → F: Abolishes interaction with NCOA1 and NCOA2. 1 Publication | 1 | |
Mutagenesisi | 502 | E → Q: Loss of transactivation function. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL1293231 |
DrugCentrali | P51450 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053518 | 1 – 516 | Nuclear receptor ROR-gammaAdd BLAST | 516 |
Proteomic databases
jPOSTi | P51450 |
MaxQBi | P51450 |
PaxDbi | P51450 |
PeptideAtlasi | P51450 |
PRIDEi | P51450 |
ProteomicsDBi | 300465 [P51450-1] 300466 [P51450-2] 300467 [P51450-3] |
PTM databases
iPTMneti | P51450 |
PhosphoSitePlusi | P51450 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000028150, Expressed in thymus and 140 other tissues |
Interactioni
Subunit structurei
Interacts (via AF-2 motif) with the coactivators NCOA1, NCOA2 and PPARGC1A (via LXXLL motif) (PubMed:16148126, PubMed:17476214, PubMed:21499262).
Interacts with the corepressor NCOR1 (PubMed:21499262).
Interacts with CRY1 (PubMed:22170608).
Interacts (via AF-2 motif) with PROX1 (PubMed:23723244).
Interacts with FOXP3 (PubMed:18368049).
Interacts with NR0B2 (PubMed:25212631).
7 PublicationsBinary interactionsi
Isoform 2 [P51450-2]
With | #Exp. | IntAct |
---|---|---|
Foxo1 [Q9R1E0] | 2 | EBI-4422078,EBI-1371343 |
Hif1a [Q61221] | 2 | EBI-4422078,EBI-298954 |
HIF1A [Q16665] from Homo sapiens. | 2 | EBI-4422078,EBI-447269 |
GO - Molecular functioni
- transcription coactivator binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 202957, 4 interactors |
DIPi | DIP-59439N |
IntActi | P51450, 8 interactors |
STRINGi | 10090.ENSMUSP00000029795 |
Chemistry databases
BindingDBi | P51450 |
Miscellaneous databases
RNActi | P51450, protein |
Structurei
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 267 – 506 | NR LBDPROSITE-ProRule annotationAdd BLAST | 240 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 30 | ModulatingSequence analysisAdd BLAST | 30 | |
Regioni | 104 – 145 | DisorderedSequence analysisAdd BLAST | 42 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 499 – 504 | AF-2 | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 117 – 134 | Polar residuesSequence analysisAdd BLAST | 18 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 31 – 51 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 67 – 91 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG4216, Eukaryota |
GeneTreei | ENSGT00940000161521 |
InParanoidi | P51450 |
OrthoDBi | 583704at2759 |
PhylomeDBi | P51450 |
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 (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative promoter usage and alternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are 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
MDRAPQRHHR TSRELLAAKK THTSQIEVIP CKICGDKSSG IHYGVITCEG
60 70 80 90 100
CKGFFRRSQQ CNVAYSCTRQ QNCPIDRTSR NRCQHCRLQK CLALGMSRDA
110 120 130 140 150
VKFGRMSKKQ RDSLHAEVQK QLQQQQQQEQ VAKTPPAGSR GADTLTYTLG
160 170 180 190 200
LSDGQLPLGA SPDLPEASAC PPGLLRASGS GPPYSNTLAK TEVQGASCHL
210 220 230 240 250
EYSPERGKAE GRDSIYSTDG QLTLGRCGLR FEETRHPELG EPEQGPDSHC
260 270 280 290 300
IPSFCSAPEV PYASLTDIEY LVQNVCKSFR ETCQLRLEDL LRQRTNLFSR
310 320 330 340 350
EEVTSYQRKS MWEMWERCAH HLTEAIQYVV EFAKRLSGFM ELCQNDQIIL
360 370 380 390 400
LTAGAMEVVL VRMCRAYNAN NHTVFFEGKY GGVELFRALG CSELISSIFD
410 420 430 440 450
FSHFLSALCF SEDEIALYTA LVLINANRPG LQEKRRVEHL QYNLELAFHH
460 470 480 490 500
HLCKTHRQGL LAKLPPKGKL RSLCSQHVEK LQIFQHLHPI VVQAAFPPLY
510
KELFSTDVES PEGLSK
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0R4J096 | A0A0R4J096_MOUSE | Nuclear receptor ROR-gamma | Rorc | 516 | Annotation score: | ||
A0A0G2JGZ6 | A0A0G2JGZ6_MOUSE | Nuclear receptor ROR-gamma | Rorc | 495 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 70 – 71 | QQ → HR in BAE32267 (PubMed:16141072).Curated | 2 | |
Sequence conflicti | 142 | A → R in BAE32267 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 181 | G → A in BAE32267 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 181 | G → D in AAB02582 (PubMed:8614404).Curated | 1 | |
Sequence conflicti | 186 | N → H in BAE32267 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 207 | G → C in BAE32267 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 352 | T → K in AAB02582 (PubMed:8614404).Curated | 1 | |
Sequence conflicti | 352 | T → K in AAD46913 (PubMed:9881970).Curated | 1 | |
Sequence conflicti | 352 | T → K in AAH14804 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056787 | 1 – 24 | MDRAP…KTHTS → MAGSYLHCA in isoform 3. CuratedAdd BLAST | 24 | |
Alternative sequenceiVSP_003659 | 1 – 21 | Missing in isoform 2. 2 PublicationsAdd BLAST | 21 | |
Alternative sequenceiVSP_003660 | 22 – 24 | HTS → MRT in isoform 2. 2 Publications | 3 | |
Alternative sequenceiVSP_056788 | 310 – 463 | Missing in isoform 3. CuratedAdd BLAST | 154 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U43508 mRNA Translation: AAB40709.1 AF019660 , AF019655, AF019656, AF019657, AF019658, AF019659 Genomic DNA Translation: AAC53501.1 U39071 mRNA Translation: AAB02582.1 AF163668 mRNA Translation: AAD46913.1 AJ132394 mRNA Translation: CAA10661.1 AK153941 mRNA Translation: BAE32267.1 AC164562 Genomic DNA No translation available. BC014804 mRNA Translation: AAH14804.1 |
CCDSi | CCDS17591.1 [P51450-1] CCDS79971.1 [P51450-2] |
PIRi | JC5375 |
RefSeqi | NP_001280663.1, NM_001293734.1 NP_035411.2, NM_011281.3 |
Genome annotation databases
Ensembli | ENSMUST00000200009; ENSMUSP00000143610; ENSMUSG00000028150 [P51450-3] |
GeneIDi | 19885 |
KEGGi | mmu:19885 |
UCSCi | uc008qfy.3, mouse [P51450-1] uc008qfz.3, mouse [P51450-2] uc012ctn.2, mouse [P51450-3] |
Keywords - Coding sequence diversityi
Alternative promoter usage, Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U43508 mRNA Translation: AAB40709.1 AF019660 , AF019655, AF019656, AF019657, AF019658, AF019659 Genomic DNA Translation: AAC53501.1 U39071 mRNA Translation: AAB02582.1 AF163668 mRNA Translation: AAD46913.1 AJ132394 mRNA Translation: CAA10661.1 AK153941 mRNA Translation: BAE32267.1 AC164562 Genomic DNA No translation available. BC014804 mRNA Translation: AAH14804.1 |
CCDSi | CCDS17591.1 [P51450-1] CCDS79971.1 [P51450-2] |
PIRi | JC5375 |
RefSeqi | NP_001280663.1, NM_001293734.1 NP_035411.2, NM_011281.3 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 202957, 4 interactors |
DIPi | DIP-59439N |
IntActi | P51450, 8 interactors |
STRINGi | 10090.ENSMUSP00000029795 |
Chemistry databases
BindingDBi | P51450 |
ChEMBLi | CHEMBL1293231 |
DrugCentrali | P51450 |
PTM databases
iPTMneti | P51450 |
PhosphoSitePlusi | P51450 |
Proteomic databases
jPOSTi | P51450 |
MaxQBi | P51450 |
PaxDbi | P51450 |
PeptideAtlasi | P51450 |
PRIDEi | P51450 |
ProteomicsDBi | 300465 [P51450-1] 300466 [P51450-2] 300467 [P51450-3] |
Protocols and materials databases
Antibodypediai | 20336, 813 antibodies from 43 providers |
DNASUi | 19885 |
Genome annotation databases
Ensembli | ENSMUST00000200009; ENSMUSP00000143610; ENSMUSG00000028150 [P51450-3] |
GeneIDi | 19885 |
KEGGi | mmu:19885 |
UCSCi | uc008qfy.3, mouse [P51450-1] uc008qfz.3, mouse [P51450-2] uc012ctn.2, mouse [P51450-3] |
Organism-specific databases
CTDi | 6097 |
MGIi | MGI:104856, Rorc |
VEuPathDBi | HostDB:ENSMUSG00000028150 |
Phylogenomic databases
eggNOGi | KOG4216, Eukaryota |
GeneTreei | ENSGT00940000161521 |
InParanoidi | P51450 |
OrthoDBi | 583704at2759 |
PhylomeDBi | P51450 |
TreeFami | TF319910 |
Enzyme and pathway databases
Reactomei | R-MMU-383280, Nuclear Receptor transcription pathway [P51450-2] |
Miscellaneous databases
BioGRID-ORCSi | 19885, 1 hit in 66 CRISPR screens |
ChiTaRSi | Rorc, mouse |
PROi | PR:P51450 |
RNActi | P51450, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000028150, Expressed in thymus and 140 other tissues |
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 | RORG_MOUSE | |
Accessioni | P51450Primary (citable) accession number: P51450 Secondary accession number(s): E9Q8I1 Q9R177 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 191 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
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families