Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Nuclear receptor ROR-gamma

Gene

Rorc

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 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 G6PC and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization.7 Publications
Isoform 2: Essential 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 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi31 – 96Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri31 – 51NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri67 – 91NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

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
  • interleukin-17 production Source: UniProtKB
  • interleukin-17 secretion Source: MGI
  • lymph node development Source: UniProtKB
  • mucosal-associated lymphoid tissue development Source: MGI
  • negative regulation of thymocyte apoptotic process Source: UniProtKB
  • 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 involved in cell fate commitment Source: UniProtKB
  • T cell differentiation in thymus Source: MGI
  • T-helper 17 cell differentiation Source: MGI
  • T-helper cell differentiation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • xenobiotic metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Receptor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-383280. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor ROR-gamma
Alternative 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:104856. Rorc.

Subcellular locationi

GO - Cellular componenti

  • intracellular membrane-bounded organelle Source: MGI
  • nucleolus Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice show decreased adipocytes size and highly insulin sensitivity, leading to an improved control of circulating fatty acids. Mutants are protected from hyperglycemia and insulin resistance in the state of obesity. Loss of circadian pattern of some clock genes expression in the peripheral tissues and massive apoptosis of thymocytes. Knockout mice for isoform 2 lack all lymph nodes and Peyer's patches, as well as LTi cells. They also show a reduction of T(H)17 cells in the lamina propria by at least 10-fold to less than 1% of the T(H) cells. Mice are less susceptible to autoimmune inflammatory diseases.4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi31C → A: Loss of adipogenesis inhibition, when associated with A-48. 1 Publication1
Mutagenesisi48C → A: Loss of adipogenesis inhibition, when associated with A-31. 1 Publication1
Mutagenesisi56 – 57RR → AG: Abolishes DNA-binding. No effect neither on interaction with NCOA1 and NCOA2 nor on inhibition of NFATC1 expression. 1 Publication2
Mutagenesisi500Y → F: Abolishes interaction with NCOA1 and NCOA2. 1 Publication1
Mutagenesisi502E → Q: Loss of transactivation function. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1293231.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535181 – 516Nuclear receptor ROR-gammaAdd BLAST516

Proteomic databases

MaxQBiP51450.
PaxDbiP51450.
PeptideAtlasiP51450.
PRIDEiP51450.

PTM databases

iPTMnetiP51450.
PhosphoSitePlusiP51450.

Expressioni

Tissue specificityi

Isoform 1 is widely expressed with highest levels in muscle, kidney and liver. Isoform 2 is expressed primarily in immature thymocytes and the subset of mature T(H)17 cells. Neither isoform is expressed in spleen or bone marrow.4 Publications

Developmental stagei

In 3T3-L1 cells, sharp decline at mRNA and protein levels upon induction of adipocyte differentiation. Isoform 2 is detected in the immediate vicinity of vessels among small clusters of CD45+ cells as early as E12.5. At E16.5, isoform 2 is expressed exclusively in tight clusters of cells found in lymph node anlagen, in the submucosal region of the intestine and around central vessels in the spleen.2 Publications

Inductioni

Isoform 1 expression oscillates diurnally in peripheral tissues such as liver, brown adipose tissue (BAT), kidney and small intestines. Isoform 2 is induced upon antigen receptor ligation in the presence of IL6 and TGB1 (via STAT3). Induced by TGFB1 in T-cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000028150.
CleanExiMM_RORC.
ExpressionAtlasiP51450. baseline and differential.

Interactioni

Subunit structurei

Interacts (via AF-2 motif) with the coactivators NCOA1, NCOA2 and PPARGC1A (via LXXLL motif). Interacts with the corepressor NCOR1. Interacts with CRY1. Interacts (via AF-2 motif) with PROX1. Interacts with FOXP3.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Foxo1Q9R1E02EBI-4422078,EBI-1371343
HIF1AQ166652EBI-4422078,EBI-447269From a different organism.
Hif1aQ612212EBI-4422078,EBI-298954

GO - Molecular functioni

  • transcription coactivator binding Source: UniProtKB

Protein-protein interaction databases

BioGridi202957. 3 interactors.
DIPiDIP-59439N.
IntActiP51450. 4 interactors.
STRINGi10090.ENSMUSP00000029795.

Chemistry databases

BindingDBiP51450.

Structurei

3D structure databases

ProteinModelPortaliP51450.
SMRiP51450.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 30ModulatingSequence analysisAdd BLAST30
Regioni97 – 266HingeSequence analysisAdd BLAST170
Regioni267 – 516Ligand-bindingSequence analysisAdd BLAST250

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi499 – 504AF-26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi119 – 130Poly-GlnAdd BLAST12

Domaini

The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2.1 Publication

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri31 – 51NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri67 – 91NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4216. Eukaryota.
ENOG410XUGR. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000010200.
HOVERGENiHBG106848.
InParanoidiP51450.
KOiK08534.
PhylomeDBiP51450.
TreeFamiTF319910.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR003079. ROR_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01293. RORNUCRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51450-1) [UniParc]FASTAAdd to basket

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
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
Note: Produced by alternative promoter usage.
Length:516
Mass (Da):58,117
Last modified:October 1, 1996 - v1
Checksum:i218068AF4598A93B
GO
Isoform 2 (identifier: P51450-2) [UniParc]FASTAAdd to basket
Also known as: RORgT

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.
     22-24: HTS → MRT

Note: Produced by alternative promoter usage.
Show »
Length:495
Mass (Da):55,696
Checksum:iA8A1C1A08921CFB6
GO
Isoform 3Curated (identifier: P51450-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: MDRAPQRHHRTSRELLAAKKTHTS → MAGSYLHCA
     310-463: Missing.

Note: Produced by alternative splicing of isoform 1.Curated
Show »
Length:347
Mass (Da):38,494
Checksum:i5F75F4DBC507BE8B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti70 – 71QQ → HR in BAE32267 (PubMed:16141072).Curated2
Sequence conflicti142A → R in BAE32267 (PubMed:16141072).Curated1
Sequence conflicti181G → A in BAE32267 (PubMed:16141072).Curated1
Sequence conflicti181G → D in AAB02582 (PubMed:8614404).Curated1
Sequence conflicti186N → H in BAE32267 (PubMed:16141072).Curated1
Sequence conflicti207G → C in BAE32267 (PubMed:16141072).Curated1
Sequence conflicti352T → K in AAB02582 (PubMed:8614404).Curated1
Sequence conflicti352T → K in AAD46913 (PubMed:9881970).Curated1
Sequence conflicti352T → K in AAH14804 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0567871 – 24MDRAP…KTHTS → MAGSYLHCA in isoform 3. CuratedAdd BLAST24
Alternative sequenceiVSP_0036591 – 21Missing in isoform 2. 2 PublicationsAdd BLAST21
Alternative sequenceiVSP_00366022 – 24HTS → MRT in isoform 2. 2 Publications3
Alternative sequenceiVSP_056788310 – 463Missing in isoform 3. CuratedAdd BLAST154

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.
CCDSiCCDS17591.1. [P51450-1]
CCDS79971.1. [P51450-2]
PIRiJC5375.
RefSeqiNP_001280663.1. NM_001293734.1.
NP_035411.2. NM_011281.3.
UniGeneiMm.4372.

Genome annotation databases

EnsembliENSMUST00000200009; ENSMUSP00000143610; ENSMUSG00000028150. [P51450-3]
GeneIDi19885.
KEGGimmu:19885.
UCSCiuc008qfy.3. mouse. [P51450-1]
uc008qfz.3. mouse. [P51450-2]
uc012ctn.2. mouse. [P51450-3]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

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.
CCDSiCCDS17591.1. [P51450-1]
CCDS79971.1. [P51450-2]
PIRiJC5375.
RefSeqiNP_001280663.1. NM_001293734.1.
NP_035411.2. NM_011281.3.
UniGeneiMm.4372.

3D structure databases

ProteinModelPortaliP51450.
SMRiP51450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202957. 3 interactors.
DIPiDIP-59439N.
IntActiP51450. 4 interactors.
STRINGi10090.ENSMUSP00000029795.

Chemistry databases

BindingDBiP51450.
ChEMBLiCHEMBL1293231.

PTM databases

iPTMnetiP51450.
PhosphoSitePlusiP51450.

Proteomic databases

MaxQBiP51450.
PaxDbiP51450.
PeptideAtlasiP51450.
PRIDEiP51450.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000200009; ENSMUSP00000143610; ENSMUSG00000028150. [P51450-3]
GeneIDi19885.
KEGGimmu:19885.
UCSCiuc008qfy.3. mouse. [P51450-1]
uc008qfz.3. mouse. [P51450-2]
uc012ctn.2. mouse. [P51450-3]

Organism-specific databases

CTDi6097.
MGIiMGI:104856. Rorc.

Phylogenomic databases

eggNOGiKOG4216. Eukaryota.
ENOG410XUGR. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000010200.
HOVERGENiHBG106848.
InParanoidiP51450.
KOiK08534.
PhylomeDBiP51450.
TreeFamiTF319910.

Enzyme and pathway databases

ReactomeiR-MMU-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiP51450.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028150.
CleanExiMM_RORC.
ExpressionAtlasiP51450. baseline and differential.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR003079. ROR_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01293. RORNUCRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRORG_MOUSE
AccessioniPrimary (citable) accession number: P51450
Secondary accession number(s): E9Q8I1
, Q3U513, Q61027, Q91YT5, Q9QXD9, Q9R177
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.