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UniProtKB - P51450 (RORG_MOUSE)

Protein

Nuclear receptor ROR-gamma

Gene

Rorc

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 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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Receptor
Biological processBiological rhythms, Transcription, Transcription regulation
LigandMetal-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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:104856 Rorc

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

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 Expressed in 109 organ(s), highest expression level in thymus
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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi202957, 4 interactors
DIPiDIP-59439N
IntActiP51450, 8 interactors
STRINGi10090.ENSMUSP00000029795

Chemistry databases

BindingDBiP51450

Structurei

3D structure databases

ProteinModelPortaliP51450
SMRiP51450
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini267 – 506NR LBDPROSITE-ProRule annotationAdd BLAST240

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 30ModulatingSequence analysisAdd BLAST30
Regioni97 – 266HingeSequence analysisAdd BLAST170

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

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

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
GeneTreeiENSGT00870000136388
HOGENOMiHOG000010200
HOVERGENiHBG106848
InParanoidiP51450
KOiK08534
PhylomeDBiP51450
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 (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0R4J096A0A0R4J096_MOUSE
Nuclear receptor ROR-gamma
Rorc
516Annotation score:
A0A0G2JGZ6A0A0G2JGZ6_MOUSE
Nuclear receptor ROR-gamma
Rorc
495Annotation score:

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

Similar 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
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, 4 interactors
DIPiDIP-59439N
IntActiP51450, 8 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
GeneTreeiENSGT00870000136388
HOGENOMiHOG000010200
HOVERGENiHBG106848
InParanoidiP51450
KOiK08534
PhylomeDBiP51450
TreeFamiTF319910

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway

Miscellaneous databases

PROiPR:P51450
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028150 Expressed in 109 organ(s), highest expression level in thymus
CleanExiMM_RORC
ExpressionAtlasiP51450 baseline and differential

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 nameiRORG_MOUSE
AccessioniPrimary (citable) accession number: P51450
Secondary accession number(s): E9Q8I1
, Q3U513, Q61027, Q91YT5, Q9QXD9, Q9R177
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 173 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, 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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