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P06537 (GCR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glucocorticoid receptor
Short name=GR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 1
Gene names
Name:Nr3c1
Synonyms:Grl, Grl1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length783 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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. Involved in chromatin remodeling. Plays a significant role in transactivation By similarity. Ref.14

Subunit structure

Heteromultimeric cytoplasmic complex with HSP90, HSP70, and FKBP5 or another immunophilin, or the immunophilin homolog PPP5C. Directly interacts with UNC45A. 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. 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, NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 By similarity. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasm. Mitochondrion By similarity. Nucleus. Note: Cytoplasmic in the absence of ligand, nuclear after ligand-binding. The hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment. Ref.8 Ref.9

Induction

Down-regulated by glucocorticoids. Ref.3 Ref.10

Domain

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Post-translational modification

Increased proteasome-mediated degradation in response to glucocorticoids.

Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoids. Ref.4

Sumoylated; this reduces transcription transactivation By similarity.

Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling. Ref.10

Miscellaneous

T-cell is a critical cellular target of GR, as immune activation in mice lacking GR resulted in significant mortality. This lethal activation is rescued by PTGS2 inhibition but not steroid administration or cytokine neutralization.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Mitochondrion
Nucleus
   Coding sequence diversityAlternative initiation
Alternative splicing
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Steroid-binding
Zinc
   Molecular functionChromatin regulator
Receptor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadrenal gland development

Inferred from mutant phenotype PubMed 7628695. Source: MGI

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

glucocorticoid metabolic process

Inferred from mutant phenotype PubMed 10509797. Source: MGI

mammary gland duct morphogenesis

Inferred from mutant phenotype PubMed 12198239. Source: MGI

positive regulation of neuron apoptotic process

Inferred from genetic interaction PubMed 10744634. Source: MGI

regulation of glucocorticoid biosynthetic process

Inferred from mutant phenotype PubMed 7628695. Source: MGI

regulation of gluconeogenesis

Inferred from mutant phenotype PubMed 7628695. Source: MGI

regulation of transcription, DNA-dependent

Inferred from direct assay PubMed 10224232. Source: MGI

transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from direct assay PubMed 7914432. Source: MGI

membrane

Inferred from direct assay PubMed 9237103. Source: MGI

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 11555636PubMed 15870285PubMed 7914432. Source: MGI

   Molecular_functionglucocorticoid receptor activity

Inferred from direct assay PubMed 15199138PubMed 7914432PubMed 9237103. Source: MGI

protein dimerization activity

Inferred from direct assay PubMed 7883868. Source: MGI

sequence-specific DNA binding

Inferred from direct assay PubMed 7883868. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

steroid binding

Inferred from electronic annotation. Source: UniProtKB-KW

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dync1i1O884852EBI-492753,EBI-492834
Fkbp4P304163EBI-492753,EBI-492746
Fkbp5Q643782EBI-492753,EBI-492796
Hsp90ab1P114992EBI-492753,EBI-492813

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: P06537-1)

Also known as: 1-A; GR form A;

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.
Isoform 2 (identifier: P06537-2)

Also known as: 2-A; GR form B;

The sequence of this isoform differs from the canonical sequence as follows:
     458-458: G → GR
Note: Produced by alternative splicing.
Isoform 1-B (identifier: P06537-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.
Note: Produced by alternative initiation at Met-28 of isoform 1.
Isoform 2-B (identifier: P06537-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.
     458-458: G → GR
Note: Produced by alternative initiation at Met-28 of isoform 2.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 783783Glucocorticoid receptor
PRO_0000019939

Regions

DNA binding425 – 50076Nuclear receptor
Zinc finger428 – 44821NR C4-type
Zinc finger464 – 48825NR C4-type
Region1 – 427427Modulating
Region494 – 53441Hinge
Region535 – 783249Steroid-binding
Compositional bias75 – 828Poly-Gln
Compositional bias407 – 42620Glu/Pro/Ser/Thr-rich (PEST region)

Amino acid modifications

Modified residue1221Phosphoserine Ref.4
Modified residue1431Phosphoserine By similarity
Modified residue1501Phosphoserine Ref.4
Modified residue1591Phosphothreonine Ref.4
Modified residue2121Phosphoserine Ref.4
Modified residue2201Phosphoserine Ref.4
Modified residue2341Phosphoserine Ref.4
Modified residue2751Phosphoserine By similarity
Modified residue3151Phosphoserine Ref.4
Cross-link285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link301Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link426Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Alternative sequence1 – 2727Missing in isoform 1-B and isoform 2-B.
VSP_018774
Alternative sequence4581G → GR in isoform 2 and isoform 2-B.
VSP_003704

Experimental info

Mutagenesis11M → T: Abolishes expression of A-type isoforms. Ref.11
Mutagenesis281M → T: Abolishes expression of B-type isoforms. 1-B. Ref.11
Mutagenesis4261K → A: Abolishes glucocorticoid-mediated degradation and enhances transcription trans-activation. Ref.10
Sequence conflict4371V → G in CAA31738. Ref.2
Sequence conflict4371V → G in CAA31739. Ref.2

Secondary structure

1 ................................ 783
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (1-A) (GR form A) [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 455E5C1C3C955F2A

FASTA78386,053
        10         20         30         40         50         60 
MDSKESLAPP GRDEVPSSLL GRGRGSVMDL YKTLRGGATV KVSASSPSVA AASQADSKQQ 

        70         80         90        100        110        120 
RILLDFSKGS ASNAQQQQQQ QQPQPDLSKA VSLSMGLYMG ETETKVMGND LGYPQQGQLG 

       130        140        150        160        170        180 
LSSGETDFRL LEESIANLNR STSRPENPKS STPAAGCATP TEKEFPQTHS DPSSEQQNRK 

       190        200        210        220        230        240 
SQPGTNGGSV KLYTTDQSTF DILQDLEFSA GSPGKETNES PWRSDLLIDE NLLSPLAGED 

       250        260        270        280        290        300 
DPFLLEGDVN EDCKPLILPD TKPKIQDTGD TILSSPSSVA LPQVKTEKDD FIELCTPGVI 

       310        320        330        340        350        360 
KQEKLGPVYC QASFSGTNII GNKMSAISVH GVSTSGGQMY HYDMNTASLS QQQDQKPVFN 

       370        380        390        400        410        420 
VIPPIPVGSE NWNRCQGSGE DNLTSLGAMN FAGRSVFSNG YSSPGMRPDV SSPPSSSSTA 

       430        440        450        460        470        480 
TGPPPKLCLV CSDEASVCHY GVLTCGSCKV FFKRAVEGQH NYLCAGRNDC IIDKIRRKNC 

       490        500        510        520        530        540 
PACRYRKCLQ AGMNLEARKT KKKIKGIQQA TAGVSQDTSE NANKTIVPAA LPQLTPTLVS 

       550        560        570        580        590        600 
LLEVIEPEVL YAGYDSSVPD SAWRIMTTLN MLGGRQVIAA VKWAKAIPGF RNLHLDDQMT 

       610        620        630        640        650        660 
LLQYSWMFLM AFALGWRSYR QASGNLLCFA PDLIINEQRM TLPCMYDQCK HMLFISTELQ 

       670        680        690        700        710        720 
RLQVSYEEYL CMKTLLLLSS VPKEGLKSQE LFDEIRMTYI KELGKAIVKR EGNSSQNWQR 

       730        740        750        760        770        780 
FYQLTKLLDS MHDVVENLLS YCFQTFLDKS MSIEFPEMLA EIITNQIPKY SNGNIKKLLF 


HQK

« Hide

Isoform 2 (2-A) (GR form B) [UniParc].

Checksum: B52F39BDEDF94ADC
Show »

FASTA78486,209
Isoform 1-B [UniParc].

Checksum: AE29F70FF47F964D
Show »

FASTA75683,273
Isoform 2-B [UniParc].

Checksum: EBD44E16FE31A015
Show »

FASTA75783,429

References

[1]"The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild-type and mutant receptor proteins."
Danielsen M., Northrop J.P., Ringold G.M.
EMBO J. 5:2513-2522(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Novel cDNA sequence possibly generated by alternative splicing of a mouse glucocorticoid receptor gene transcript from Shionogi carcinoma 115."
Nohno T., Kasai Y., Saito T.
Nucleic Acids Res. 17:445-445(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-755 (ISOFORMS 1 AND 2).
[3]"Regulation of glucocorticoid receptor protein and mRNA levels."
Vedeckis W.V., Ali M., Allen H.R.
Cancer Res. 49:2295-2302(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: GLUCOCORTICOID-MEDIATED DOWN-REGULATION.
[4]"Identification of phosphorylated sites in the mouse glucocorticoid receptor."
Bodwell J.E., Orti E., Coull J.M., Pappin D.J.C., Smith L.I., Swift F.
J. Biol. Chem. 266:7549-7555(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-122; SER-150; THR-159; SER-212; SER-220; SER-234 AND SER-315.
[5]"Characterization of Stat5a and Stat5b homodimers and heterodimers and their association with the glucocortiocoid receptor in mammary cells."
Cella N., Groner B., Hynes N.E.
Mol. Cell. Biol. 18:1783-1792(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STA5A AND STAT5B.
[6]"Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression."
Chang C.J., Chen Y.L., Lee S.C.
Mol. Cell. Biol. 18:5880-5887(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM28.
[7]"Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix."
Yang L., Guerrero J., Hong H., DeFranco D.B., Stallcup M.R.
Mol. Biol. Cell 11:2007-2018(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[8]"The glucocorticoid receptor: rapid exchange with regulatory sites in living cells."
McNally J.G., Mueller W.G., Walker D., Wolford R., Hager G.L.
Science 287:1262-1265(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION OF REGULATORY PROTEINS WITH TARGET SITES IN CHROMATIN.
[9]"Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus."
Galigniana M.D., Radanyi C., Renoir J.-M., Housley P.R., Pratt W.B.
J. Biol. Chem. 276:14884-14889(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, HETEROMULTIMERIC COMPLEX FORMATION, INTERACTION WITH FKBP4, MECHANISM OF TRANSLOCATION TO THE NUCLEUS.
[10]"Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids."
Wallace A.D., Cidlowski J.A.
J. Biol. Chem. 276:42714-42721(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-426, MUTAGENESIS OF LYS-426, GLUCOCORTICOID-MEDIATED DOWN-REGULATION.
[11]"Molecular identification and characterization of A and B forms of the glucocorticoid receptor."
Yudt M.R., Cidlowski J.A.
Mol. Endocrinol. 15:1093-1103(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE INITIATION, MUTAGENESIS OF MET-1 AND MET-28.
[12]"A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins."
Davies T.H., Ning Y.M., Sanchez E.R.
J. Biol. Chem. 277:4597-4600(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: HETEROMULTIMERIC COMPLEX FORMATION, MECHANISM OF TRANSLOCATION TO THE NUCLEUS.
[13]"T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation."
Brewer J.A., Khor B., Vogt S.K., Muglia L.M., Fujiwara H., Haegele K.E., Sleckman B.P., Muglia L.J.
Nat. Med. 9:1318-1322(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IMMUNE SYSTEM DEVELOPMENT.
[14]"Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth."
Tronche F., Opherk C., Moriggl R., Kellendonk C., Reimann A., Schwake L., Reichardt H.M., Stangl K., Gau D., Hoeflich A., Beug H., Schmid W., Schuetz G.
Genes Dev. 18:492-497(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE FUNCTION IN THE CONTROL OF BODY GROWTH.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X04435 mRNA. Translation: CAA28031.1.
X13358 mRNA. Translation: CAA31738.1.
X13359 mRNA. Translation: CAA31739.1.
IPIIPI00125443.
IPI00230717.
IPI00759971.
IPI00856515.
PIRA25691.
UniGeneMm.129481.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MNEX-ray1.96A527-783[»]
3MNOX-ray1.55A527-783[»]
3MNPX-ray1.50A527-783[»]
ProteinModelPortalP06537.
SMRP06537. Positions 425-782.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-11N.
IntActP06537. 4 interactions.

PTM databases

PhosphoSiteP06537.

Proteomic databases

PaxDbP06537.
PRIDEP06537.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCuc008esy.1. mouse.

Organism-specific databases

MGIMGI:95824. Nr3c1.

Phylogenomic databases

eggNOGNOG270250.
HOGENOMHOG000037950.
HOVERGENHBG007583.

Gene expression databases

CleanExMM_NR3C1.
GenevestigatorP06537.
GermOnlineENSMUSG00000024431. Mus musculus.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR001409. Glcrtcd_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF02155. GCR. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00528. GLCORTICOIDR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. Str_ncl_receptor. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP06537.
ChEMBLCHEMBL3144.
ChiTaRSNR3C1. mouse.
EvolutionaryTraceP06537.
SOURCESearch...

Entry information

Entry nameGCR_MOUSE
AccessionPrimary (citable) accession number: P06537
Secondary accession number(s): Q61628, Q61629
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: April 3, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents