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Protein

Glucocorticoid receptor

Gene

NR3C1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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. 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. 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)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi416 – 48166Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri416 – 43621NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri452 – 47625NR C4-typePROSITE-ProRule annotationAdd
BLAST

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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Mitochondrion By similarity
  • Cytoplasmcytoskeletonspindle By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity

  • Note: After ligand activation, translocates from the cytoplasm to the nucleus.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 772772Glucocorticoid receptorPRO_0000053673Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei115 – 1151PhosphoserineBy similarity
Modified residuei136 – 1361PhosphoserineBy similarity
Modified residuei143 – 1431PhosphoserineBy similarity
Modified residuei203 – 2031PhosphoserineBy similarity
Modified residuei211 – 2111PhosphoserineBy similarity
Modified residuei226 – 2261PhosphoserineBy similarity
Cross-linki277 – 277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki293 – 293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei307 – 3071PhosphoserineBy similarity
Modified residuei400 – 4001PhosphoserineBy similarity
Cross-linki414 – 414Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei475 – 4751N6-acetyllysineBy similarity
Modified residuei487 – 4871N6-acetyllysineBy similarity
Modified residuei489 – 4891N6-acetyllysineBy similarity
Modified residuei490 – 4901N6-acetyllysineBy similarity
Cross-linki698 – 698Glycyl 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-399-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-399 decreases signaling capacity. Phosphorylation at Ser-399 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-698 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-277 and Lys-293 is dispensable whereas sumoylation at Lys-698 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, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:9195923). 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 (PubMed:9195923). 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 (By similarity). Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (By similarity). Interaction with BAG1 inhibits transactivation (By similarity). Interacts with HEXIM1, PELP1 and TGFB1I1 (By similarity). Interacts with NCOA1 (By similarity). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (By similarity). Interacts with CIART (By similarity). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with GRIP1 (By similarity). 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).By similarity

Protein-protein interaction databases

BioGridi1171913. 1 interaction.
STRINGi9986.ENSOCUP00000010039.

Structurei

3D structure databases

ProteinModelPortaliP59667.
SMRiP59667. Positions 412-490, 518-772.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 415415ModulatingAdd
BLAST
Regioni480 – 772293Interaction with CLOCKBy similarityAdd
BLAST
Regioni482 – 52241HingeAdd
BLAST
Regioni527 – 692166Interaction with CRY1By similarityAdd
BLAST
Regioni528 – 772245Steroid-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi395 – 41420Glu/Pro/Ser/Thr-rich (PEST region)Add
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri416 – 43621NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri452 – 47625NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000037950.
HOVERGENiHBG007583.
InParanoidiP59667.
KOiK05771.

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.

P59667-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSKESLSPP GREEVPSSVL RPAERGNVMD LYKTLRGGAP VRVPASSPSL
60 70 80 90 100
APAAQPDSKQ QRLAVDFPKG SASNAQQPDL SRAVSLSMGL YMGETETKVM
110 120 130 140 150
GSDLAFPQQG QTSLSSGETD FRLLEESIAS LNRSASGADN PRSTAPAAGS
160 170 180 190 200
AAPTEGFPKT HSDLASERQN PKGQTGGSAG SAKLHPTDQS TFDILQDLEF
210 220 230 240 250
SGSPSKDRSE SPWRSDLLMD ENCLLSPLAG EDDPFLLEGN SSEDCKPLIL
260 270 280 290 300
PDTKPKIKDN GDLILSNSNN VPLPQVKTEK EDFIELCTPG VIKQEKLGPV
310 320 330 340 350
YCQASFSGAN IIGNKISAIS VHGVSTSGGQ MYHYDMNAQQ QEQKPLFNVI
360 370 380 390 400
PPIPVGSENW NRCQGSGDDN LTSLGTMNFP GRSVFSNGYS SPGMRPDVSS
410 420 430 440 450
PPSNSTTAAG PPPKLCLVCS DEASGCHYGV LTCGSCKVFF KRAVKGQHNY
460 470 480 490 500
LCAGRNDCII DKIRRKNCPA CRYRKCLQAG MNLEARKTKK KIKGIQQTST
510 520 530 540 550
GVSQETSENP SNRTVVPAAL PQLTPTLVSL LEVIEPEVLY AGYDSSVPDS
560 570 580 590 600
TWRIMTTLNM LGGRQVIAAV KWAKAIPGFR NLHLDDQMTL LQYSWMFLMA
610 620 630 640 650
FALGWRSYKQ SSGNMLCFAP DLVINEQRMT LPYMYDQCKH MLFVSSELKR
660 670 680 690 700
LQVSYEEYLC MKTLLLLSTV PKEGLKSQEL FDEIRMTYIK ELGKAIVKRE
710 720 730 740 750
GNSSQNWQRF YQLTKLLDSM HEVVENLLHY CFQTFLDKTM SIEFPEMLAE
760 770
IITNQIPKYS NGNIKKLLFH QK
Length:772
Mass (Da):84,863
Last modified:April 30, 2003 - v1
Checksum:iC16D6CF799F83148
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY161275 mRNA. Translation: AAN75442.1.
RefSeqiNP_001075616.1. NM_001082147.1.
UniGeneiOcu.6308.

Genome annotation databases

GeneIDi100008890.
KEGGiocu:100008890.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY161275 mRNA. Translation: AAN75442.1.
RefSeqiNP_001075616.1. NM_001082147.1.
UniGeneiOcu.6308.

3D structure databases

ProteinModelPortaliP59667.
SMRiP59667. Positions 412-490, 518-772.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1171913. 1 interaction.
STRINGi9986.ENSOCUP00000010039.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100008890.
KEGGiocu:100008890.

Organism-specific databases

CTDi2908.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000037950.
HOVERGENiHBG007583.
InParanoidiP59667.
KOiK05771.

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...

Publicationsi

  1. "Rabbit glucocorticoid receptor from lens epithelial cells."
    James E.R., Robertson L.L.
    Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lens epithelium.
  2. "Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin."
    Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K., Chinkers M., Pratt W.B.
    J. Biol. Chem. 272:16224-16230(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH NR3C1 AND FKBP4; PPID; PPP5C OR STIP1.

Entry informationi

Entry nameiGCR_RABIT
AccessioniPrimary (citable) accession number: P59667
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: April 30, 2003
Last modified: June 8, 2016
This is version 102 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. 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.