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Protein

Glucocorticoid receptor

Gene

NR3C1

Organism
Saimiri sciureus (Common squirrel monkey)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for glucocorticoids (GC) (PubMed:10775802, PubMed:11703081). 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 (PubMed:10775802, PubMed:11703081, PubMed:15857751). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (By similarity). 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). Mediates glucocorticoid-induced apoptosis (By similarity). Promotes accurate chromosome segregation during mitosis (By similarity). May act as a tumor suppressor (By similarity). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity).By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi421 – 486Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri421 – 441NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri457 – 481NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-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
OrganismiSaimiri sciureus (Common squirrel monkey)
Taxonomic identifieri9521 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniPlatyrrhiniCebidaeSaimiriinaeSaimiri

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi120Q → L: No effect on nuclear translocation or transactivation. 1 Publication1
Mutagenesisi210Q → E: No effect on nuclear translocation or transactivation. 1 Publication1
Mutagenesisi517A → G: No effect on nuclear translocation. 1 Publication1
Mutagenesisi552T → S: Increased nuclear translocation; when associated with S-617 and A-619. 1 Publication1
Mutagenesisi617A → S: Increased nuclear translocation. when associated with S-552 and A-619. 1 Publication1
Mutagenesisi619S → A: Increased nuclear translocation. when associated with S-552 and S-617. 1 Publication1
Mutagenesisi762L → I: No effect on nuclear translocation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536761 – 778Glucocorticoid receptorAdd BLAST778

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8PhosphothreonineBy similarity1
Modified residuei23Omega-N-methylarginineBy similarity1
Modified residuei45PhosphoserineBy similarity1
Modified residuei113PhosphoserineBy similarity1
Modified residuei134PhosphoserineBy similarity1
Modified residuei141PhosphoserineBy similarity1
Modified residuei203PhosphoserineBy similarity1
Modified residuei211PhosphoserineBy similarity1
Modified residuei226PhosphoserineBy similarity1
Modified residuei267PhosphoserineBy similarity1
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei404PhosphoserineBy similarity1
Modified residuei480N6-acetyllysineBy similarity1
Modified residuei492N6-acetyllysineBy similarity1
Modified residuei494N6-acetyllysineBy similarity1
Modified residuei495N6-acetyllysineBy similarity1
Cross-linki704Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

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 glucocorticoid. The Ser-203, Ser-226 and Ser-404-phosphorylated forms are mainly cytoplasmic, and the Ser-211-phosphorylated form is nuclear. Phosphorylation at Ser-211 increases transcriptional activity. Phosphorylation at Ser-203, Ser-226 and Ser-404 decreases signaling capacity. Phosphorylation at Ser-404 may protect from glucocorticoid-induced apoptosis. Phosphorylation at Ser-203 and Ser-211 is not required in regulation of chromosome segregation. May be dephosphorylated by PPP5C, attenuates NR3C1 action.By similarity
Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling.By similarity
Sumoylation at Lys-277 and Lys-293 negatively regulates its transcriptional activity. Sumoylation at Lys-704 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-277 and Lys-293 is dispensable whereas sumoylation at Lys-704 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWDD3-dependent manner.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Expressioni

Tissue specificityi

Expressed in brain. Regions of high expression include CA1 and CA2 of hippocampus, dentate gyrus, paraventricular hypothalamus, lateral geniculate, lateral-medial amygdala, and cerebellum. In the cerebral cortex, laminar patterns of expression were apparent in all cortical layers, particularly the pyramidal cell-rich layers II/III and V.1 Publication

Inductioni

Binding activity reduced by FKBP5.1 Publication

Interactioni

Subunit structurei

Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C. 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. Directly interacts with UNC45A. Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers. Interacts with NRIP1, POU2F1, POU2F2 and TRIM28. Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6. Interaction with BAG1 inhibits transactivation. Interacts with HEXIM1, PELP1 and TGFB1I1. Interacts with NCOA1. Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1. Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion. Interacts with CIART. Interacts with RWDD3. Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3. Interacts with GRIP1. Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation. Interacts with GSK3B. Interacts with FNIP1 and FNIP2.By similarity

Structurei

3D structure databases

ProteinModelPortaliO46567.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 420ModulatingAdd BLAST420
Regioni485 – 778Interaction with CLOCKBy similarityAdd BLAST294
Regioni487 – 527HingeAdd BLAST41
Regioni528 – 778Steroid-bindingAdd BLAST251
Regioni533 – 698Interaction with CRY1By similarityAdd BLAST166

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi399 – 419Glu/Pro/Ser/Thr-rich (PEST region)Add BLAST21

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

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri421 – 441NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri457 – 481NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

HOVERGENiHBG007583.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR001409. Glcrtcd_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF02155. GCR. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00528. GLCORTICOIDR.
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]

Sequencei

Sequence statusi: Complete.

O46567-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSKESLTPG KEENPSSVLT QERGNVMDFC KILRGGATLK VSVSSTSLAA
60 70 80 90 100
ASQSDSKQQR LLVDFPKGSV SNAQQPDLSK AVSLSMGLYM GETETKVMGN
110 120 130 140 150
DLGFPQQGQI SLSSGETDLQ LLEESIANLN RSTSVPENPK SSASSSVSAA
160 170 180 190 200
PKEKEFPKTH SDVSSEQQNL KGQTGTNGGN VKLYTADQST FDILQDLEFS
210 220 230 240 250
SGSPGKETNQ SPWKSDLLID ENCLLSPLAG EEDSFLLEGN SNEDCKPLIL
260 270 280 290 300
PDTKPKIKDN GDLVLSSSSN VTLPQVKTEK EDFIELCTPG VIKQEKLSTV
310 320 330 340 350
YCQASFPGAN IIGNKMSAIS IHGVSTSGGQ MYHYDMNTAS LSQQQDQKPI
360 370 380 390 400
FNVIPPIPVG SENWNRCQGS GDDNLTSLGT LNFPGRTVFS NGYSSPSMRP
410 420 430 440 450
DVSSPPSSSS TATTGPPPKL CLVCSDEASG CHYGVLTCGS CKVFFKRAVE
460 470 480 490 500
GQHNYLCAGR NDCIIDKIRR KNCPACRYRK CLQAGMNLEA RKTKKKIIKG
510 520 530 540 550
IQQATTGVSQ ETSENPANKT IVPATLPQLT PTLVSLLEVI EPEVLYAGYD
560 570 580 590 600
STVPDSTWRI MTTLNMLGGR QVIAAVKWAK AIPGFRNLHL DDQMTLLQYS
610 620 630 640 650
WMFLMAFALG WRSYRQASSN LLCFAPDLII NEQRMTLPCM YDQCKHMLYV
660 670 680 690 700
SSELHRLQVS YEEYLCMKTL LLLSSVPKDG LKSQELFDEI RMTYIKELGK
710 720 730 740 750
AIVKREGNSS QNWQRFYQLT KLLDSMHEVV ENLLNYCFQT FLDKTMSIEF
760 770
PEMLAEIITN QLPKYSNGNI KKLLFHQK
Length:778
Mass (Da):85,738
Last modified:June 1, 1998 - v1
Checksum:i721B8203939D1389
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti498Missing in AAK01303 (PubMed:11703081).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041834 mRNA. Translation: AAB97369.1.
AF337042 mRNA. Translation: AAK01303.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041834 mRNA. Translation: AAB97369.1.
AF337042 mRNA. Translation: AAK01303.1.

3D structure databases

ProteinModelPortaliO46567.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG007583.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR001409. Glcrtcd_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF02155. GCR. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00528. GLCORTICOIDR.
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 nameiGCR_SAISC
AccessioniPrimary (citable) accession number: O46567
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. 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.