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

Glucocorticoid receptor

Gene

Nr3c1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:12917342). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (By similarity). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity).By similarity1 Publication
Isoform A: Has transcriptional activation and repression activity. Mediates glucocorticoid-induced apoptosis. Promotes accurate chromosome segregation during mitosis. May act as a tumor suppressor. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi440 – 505Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri440 – 460NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri476 – 500NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, DNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandLipid-binding, Metal-binding, Steroid-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Glucocorticoid receptor
Short name:
GR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 1
Gene namesi
Name:Nr3c1
Synonyms:Grl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2741 Nr3c1

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

Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1M → T: Abolishes expression of A-type isoforms. 1 Publication1
Mutagenesisi28M → T: Abolishes expression of B-type isoforms. 1 Publication1
Mutagenesisi297K → R: Enhances transcriptional activity; when associated with R-313. 1 Publication1
Mutagenesisi313K → R: Enhances transcriptional activity; when associated with R-297. 1 Publication1
Mutagenesisi481D → R: Disrupts dimerization and decreases transcription transactivation. 1 Publication1
Mutagenesisi488R → Q: Loss of chromatin specific function and reduces chromatin remodeling. Abolishes interaction with SMARD1. 1 Publication1
Mutagenesisi500C → Y: Abolishes interaction with POU2F2. 1 Publication1
Mutagenesisi501L → P: Abrogates DNA-binding and transcription transactivation. Abolishes interaction with POU2F1 and POU2F2. 2 Publications1
Mutagenesisi656C → S: Strongly increases affinity for dexamethasone. 1 Publication1
Mutagenesisi721K → R: Abolishes the stimulatory effect of RWDD3 on its transcriptional activity. Diminishes NCOA2 coactivator activity. 1 Publication1
Mutagenesisi773E → A: Abolishes interaction with NCOA1 and reduces transcription transactivation; when associated with S-656. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3368

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000199411 – 795Glucocorticoid receptorAdd BLAST795

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24Omega-N-methylarginineBy similarity1
Modified residuei46PhosphoserineBy similarity1
Modified residuei134PhosphoserineBy similarity1
Modified residuei155PhosphoserineBy similarity1
Modified residuei162PhosphoserineBy similarity1
Modified residuei171Phosphothreonine1 Publication1
Modified residuei224PhosphoserineCombined sources1 Publication1
Modified residuei232PhosphoserineCombined sources1 Publication1
Modified residuei246Phosphoserine1 Publication1
Cross-linki278Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei287PhosphoserineCombined sources1
Cross-linki297Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki297Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki313Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki313Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei327PhosphoserineBy similarity1
Modified residuei424PhosphoserineBy similarity1
Cross-linki438Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei499N6-acetyllysineBy similarity1
Modified residuei511N6-acetyllysineBy similarity1
Modified residuei513N6-acetyllysineBy similarity1
Modified residuei514N6-acetyllysineBy similarity1
Cross-linki721Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Post-translational modificationi

Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity.By similarity
Increased proteasome-mediated degradation in response to glucocorticoids.By similarity
Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoids. The Ser-224, Ser-246 and Ser-424-phosphorylated forms are mainly cytoplasmic, and the Ser-232-phosphorylated form is nuclear. Phosphorylation at Ser-232 increases transcriptional activity. Phosphorylation at Ser-224, Ser-246 and Ser-424 decreases signaling capacity. Phosphorylation at Ser-424 may protect from glucocorticoid-induced apoptosis. Phosphorylation at Ser-224 and Ser-232 is not required in regulation of chromosome segregation. May be dephosphorylated by PPP5C, attenuates NR3C1 action.By similarity
Sumoylation at Lys-297 and Lys-313 negatively regulates its transcriptional activity. Sumoylation at Lys-721 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-297 and Lys-313 is dispensable whereas sumoylation at Lys-721 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWDD3-dependent manner.1 Publication
Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP06536
PeptideAtlasiP06536
PRIDEiP06536

PTM databases

iPTMnetiP06536
PhosphoSitePlusiP06536

Interactioni

Subunit structurei

Interacts with GRIP1 (By similarity). Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:21730050). Upon ligand binding FKBP5 dissociates from the complex and FKBP4 takes its place, thereby linking the complex to dynein and mediating transport to the nucleus, where the complex dissociates (By similarity). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Directly interacts with UNC45A (By similarity). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor (By similarity). Binds STAT5A and STAT5B homodimers and heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (PubMed:10364267, PubMed:10480874). Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (PubMed:9111344, PubMed:10866662). Interaction with BAG1 inhibits transactivation (By similarity). Interacts with HEXIM1, PELP1 and TGFB1I1 (By similarity). Interacts with NCOA1 (PubMed:12917342). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (PubMed:12917342, PubMed:12118039). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (By similarity). Interacts with CIART (By similarity). Interacts with RWDD3 (PubMed:23508108). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (PubMed:23508108). Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (By similarity). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (By similarity). Interacts with GSK3B (By similarity). Interacts with FNIP1 and FNIP2 (By similarity). Interacts (via C-terminus) with HNRNPU (via C-terminus) (By similarity).By similarity8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi246578, 15 interactors
CORUMiP06536
DIPiDIP-38940N
ELMiP06536
IntActiP06536, 34 interactors
STRINGi10116.ENSRNOP00000044335

Chemistry databases

BindingDBiP06536

Structurei

Secondary structure

1795
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP06536
SMRiP06536
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06536

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini542 – 776NR LBDPROSITE-ProRule annotationAdd BLAST235

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 439ModulatingAdd BLAST439
Regioni504 – 795Interaction with CLOCKBy similarityAdd BLAST292
Regioni506 – 541HingeAdd BLAST36
Regioni550 – 715Interaction with CRY1By similarityAdd BLAST166

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi75 – 97Poly-GlnAdd BLAST23
Compositional biasi419 – 438Glu/Pro/Ser/Thr-rich (PEST region)Add BLAST20

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required.By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri440 – 460NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri476 – 500NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
HOGENOMiHOG000037950
HOVERGENiHBG007583
InParanoidiP06536
KOiK05771
PhylomeDBiP06536

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR001409 Glcrtcd_rcpt
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF02155 GCR, 2 hits
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00528 GLCORTICOIDR
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket
Isoform A (identifier: P06536-1) [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
MDSKESLAPP GRDEVPGSLL GQGRGSVMDF YKSLRGGATV KVSASSPSVA
60 70 80 90 100
AASQADSKQQ RILLDFSKGS TSNVQQRQQQ QQQQQQQQQQ QQQQQQPDLS
110 120 130 140 150
KAVSLSMGLY MGETETKVMG NDLGYPQQGQ LGLSSGETDF RLLEESIANL
160 170 180 190 200
NRSTSVPENP KSSTSATGCA TPTEKEFPKT HSDASSEQQN RKSQTGTNGG
210 220 230 240 250
SVKLYPTDQS TFDLLKDLEF SAGSPSKDTN ESPWRSDLLI DENLLSPLAG
260 270 280 290 300
EDDPFLLEGN TNEDCKPLIL PDTKPKIKDT GDTILSSPSS VALPQVKTEK
310 320 330 340 350
DDFIELCTPG VIKQEKLGPV YCQASFSGTN IIGNKMSAIS VHGVSTSGGQ
360 370 380 390 400
MYHYDMNTAS LSQQQDQKPV FNVIPPIPVG SENWNRCQGS GEDSLTSLGA
410 420 430 440 450
LNFPGRSVFS NGYSSPGMRP DVSSPPSSSS AATGPPPKLC LVCSDEASGC
460 470 480 490 500
HYGVLTCGSC KVFFKRAVEG QHNYLCAGRN DCIIDKIRRK NCPACRYRKC
510 520 530 540 550
LQAGMNLEAR KTKKKIKGIQ QATAGVSQDT SENPNKTIVP AALPQLTPTL
560 570 580 590 600
VSLLEVIEPE VLYAGYDSSV PDSAWRIMTT LNMLGGRQVI AAVKWAKAIL
610 620 630 640 650
GLRNLHLDDQ MTLLQYSWMF LMAFALGWRS YRQSSGNLLC FAPDLIINEQ
660 670 680 690 700
RMSLPCMYDQ CKHMLFVSSE LQRLQVSYEE YLCMKTLLLL SSVPKEGLKS
710 720 730 740 750
QELFDEIRMT YIKELGKAIV KREGNSSQNW QRFYQLTKLL DSMHEVVENL
760 770 780 790
LTYCFQTFLD KTMSIEFPEM LAEIITNQIP KYSNGNIKKL LFHQK
Length:795
Mass (Da):87,556
Last modified:November 1, 1995 - v2
Checksum:i9C9DE0B1D6724845
GO
Isoform B (identifier: P06536-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.

Show »
Length:768
Mass (Da):84,834
Checksum:iD6E586FE0E91597F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti95 – 96Missing in AAL78956 (Ref. 3) Curated2
Sequence conflicti98D → G in AAA41203 (PubMed:3755378).Curated1
Sequence conflicti345S → T in CAA68545 (PubMed:3684608).Curated1
Sequence conflicti600L → P in CAA72938 (Ref. 2) Curated1
Sequence conflicti600L → P in AAL66772 (Ref. 3) Curated1
Sequence conflicti600L → P in AAL78956 (Ref. 3) Curated1
Sequence conflicti602L → F in AAL66772 (Ref. 3) Curated1
Sequence conflicti602L → F in AAL78956 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti77Missing in strain: Brown Norway/Crl. 1
Natural varianti78 – 79Missing in strain: SHR/OlaIpcv. 2
Natural varianti83 – 96Missing in strain: Sprague-Dawley. Add BLAST14
Natural varianti226S → G in strain: SHR/OlaIpcv and Brown Norway/Crl. Combined sources1 Publication1
Natural varianti260N → D in strain: SHR/OlaIpcv and Brown Norway/Crl. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0189691 – 27Missing in isoform B. CuratedAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14053 mRNA Translation: AAA41203.1
Y12264 mRNA Translation: CAA72938.1
AY066016 mRNA Translation: AAL66772.2
AF455050 mRNA Translation: AAL78956.1
Y00489 mRNA Translation: CAA68545.1
X69666 Genomic DNA No translation available.
X69667 Genomic DNA No translation available.
X69668 Genomic DNA No translation available.
X69669 Genomic DNA No translation available.
X69670 Genomic DNA No translation available.
PIRiA24194 QRRTG
RefSeqiNP_036708.2, NM_012576.2
UniGeneiRn.90070

Genome annotation databases

GeneIDi24413
KEGGirno:24413
UCSCiRGD:2741 rat [P06536-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14053 mRNA Translation: AAA41203.1
Y12264 mRNA Translation: CAA72938.1
AY066016 mRNA Translation: AAL66772.2
AF455050 mRNA Translation: AAL78956.1
Y00489 mRNA Translation: CAA68545.1
X69666 Genomic DNA No translation available.
X69667 Genomic DNA No translation available.
X69668 Genomic DNA No translation available.
X69669 Genomic DNA No translation available.
X69670 Genomic DNA No translation available.
PIRiA24194 QRRTG
RefSeqiNP_036708.2, NM_012576.2
UniGeneiRn.90070

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GDCNMR-A439-510[»]
1GLUX-ray2.90A/B440-514[»]
1LATX-ray1.90A/B440-515[»]
1R4OX-ray2.50A/B440-525[»]
1R4RX-ray3.00A/B440-525[»]
1RGDNMR-A440-510[»]
2GDANMR-A439-510[»]
3FYLX-ray1.63A/B440-525[»]
3G6PX-ray1.99A/B440-525[»]
3G6QX-ray2.26A/B440-525[»]
3G6RX-ray2.30A/B440-525[»]
3G6TX-ray1.90A/B440-525[»]
3G6UX-ray1.90A/B440-525[»]
3G8UX-ray1.90A/B440-525[»]
3G8XX-ray2.05A/B440-525[»]
3G97X-ray2.08A/B440-525[»]
3G99X-ray1.81A/B440-525[»]
3G9IX-ray1.85A/B440-525[»]
3G9JX-ray2.32A/B440-525[»]
3G9MX-ray1.61A/B440-525[»]
3G9OX-ray1.65A/B440-525[»]
3G9PX-ray1.65A/B440-525[»]
ProteinModelPortaliP06536
SMRiP06536
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246578, 15 interactors
CORUMiP06536
DIPiDIP-38940N
ELMiP06536
IntActiP06536, 34 interactors
STRINGi10116.ENSRNOP00000044335

Chemistry databases

BindingDBiP06536
ChEMBLiCHEMBL3368

PTM databases

iPTMnetiP06536
PhosphoSitePlusiP06536

Proteomic databases

PaxDbiP06536
PeptideAtlasiP06536
PRIDEiP06536

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24413
KEGGirno:24413
UCSCiRGD:2741 rat [P06536-1]

Organism-specific databases

CTDi2908
RGDi2741 Nr3c1

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
HOGENOMiHOG000037950
HOVERGENiHBG007583
InParanoidiP06536
KOiK05771
PhylomeDBiP06536

Miscellaneous databases

EvolutionaryTraceiP06536
PROiPR:P06536

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR001409 Glcrtcd_rcpt
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF02155 GCR, 2 hits
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00528 GLCORTICOIDR
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 nameiGCR_RAT
AccessioniPrimary (citable) accession number: P06536
Secondary accession number(s): O08624, Q8R463, Q8R5J0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 1, 1995
Last modified: September 12, 2018
This is version 214 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again