Swiss-Prot entry
ID GCR_MOUSE STANDARD; PRT; 783 AA.
AC P06537; Q61628; Q61629;
DT 01-JAN-1988 (Rel. 06, Created)
DT 01-JAN-1988 (Rel. 06, Last sequence update)
DT 01-MAY-2005 (Rel. 47, Last annotation update)
DE Glucocorticoid receptor (GR).
GN Name=Nr3c1; Synonyms=Grl, Grl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muridae; Murinae; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RX MEDLINE=87053816; PubMed=3780669 [NCBI, ExPASy, EBI, Israel, Japan];
RA Danielsen M., Northrop J.P., Ringold G.M.;
RT "The mouse glucocorticoid receptor: mapping of functional domains by
RT cloning, sequencing and expression of wild-type and mutant receptor
RT proteins.";
RL EMBO J. 5:2513-2522(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE OF 1-755 (ISOFORMS 1 AND 2).
RX MEDLINE=89098404; PubMed=2911477 [NCBI, ExPASy, EBI, Israel, Japan];
RA Nohno T., Kasai Y., Saito T.;
RT "Novel cDNA sequence possibly generated by alternative splicing of a
RT mouse glucocorticoid receptor gene transcript from Shionogi carcinoma
RT 115.";
RL Nucleic Acids Res. 17:445-445(1989).
RN [3]
RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION.
RX MEDLINE=89195167; PubMed=2702670 [NCBI, ExPASy, EBI, Israel, Japan];
RA Vedeckis W.V., Ali M., Allen H.R.;
RT "Regulation of glucocorticoid receptor protein and mRNA levels.";
RL Cancer Res. 49:2295-2302(1989).
RN [4]
RP PHOSPHORYLATION SITES SER-122; SER-150; THR-159; SER-212; SER-220;
RP SER-234 AND SER-315.
RX MEDLINE=91210266; PubMed=2019585 [NCBI, ExPASy, EBI, Israel, Japan];
RA Bodwell J.E., Orti E., Coull J.M., Pappin D.J.C., Smith L.I.,
RA Swift F.;
RT "Identification of phosphorylated sites in the mouse glucocorticoid
RT receptor.";
RL J. Biol. Chem. 266:7549-7555(1991).
RN [5]
RP INTERACTION WITH STA5A AND STAT5B.
RX MEDLINE=98187599; PubMed=9528750 [NCBI, ExPASy, EBI, Israel, Japan];
RA Cella N., Groner B., Hynes N.E.;
RT "Characterization of Stat5a and Stat5b homodimers and heterodimers and
RT their association with the glucocortiocoid receptor in mammary
RT cells.";
RL Mol. Cell. Biol. 18:1783-1792(1998).
RN [6]
RP INTERACTION WITH TRIM28.
RX PubMed=9742105 [NCBI, ExPASy, EBI, Israel, Japan];
RA Chang C.J., Chen Y.L., Lee S.C.;
RT "Coactivator TIF1beta interacts with transcription factor C/EBPbeta
RT and glucocorticoid receptor to induce alpha1-acid glycoprotein gene
RT expression.";
RL Mol. Cell. Biol. 18:5880-5887(1998).
RN [7]
RP INTERACTION WITH TGFB1I1.
RX MEDLINE=20307392; PubMed=10848625 [NCBI, ExPASy, EBI, Israel, Japan];
RA Yang L., Guerrero J., Hong H., DeFranco D.B., Stallcup M.R.;
RT "Interaction of the tau2 transcriptional activation domain of
RT glucocorticoid receptor with a novel steroid receptor coactivator,
RT Hic-5, which localizes to both focal adhesions and the nuclear
RT matrix.";
RL Mol. Biol. Cell 11:2007-2018(2000).
RN [8]
RP SUBCELLULAR LOCATION, HETEROMULTIMERIC COMPLEX FORMATION, INTERACTION
RP WITH FKBP4, AND MECHANISM OF TRANSLOCATION TO THE NUCLEUS.
RX MEDLINE=21226725; PubMed=11278753 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.M010809200;
RA Galigniana M.D., Radanyi C., Renoir J.-M., Housley P.R., Pratt W.B.;
RT "Evidence that the peptidylprolyl isomerase domain of the hsp90-
RT binding immunophilin FKBP52 is involved in both dynein interaction and
RT glucocorticoid receptor movement to the nucleus.";
RL J. Biol. Chem. 276:14884-14889(2001).
RN [9]
RP UBIQUITINATION, MUTAGENESIS OF LYS-426, AND GLUCOCORTICOID-MEDIATED
RP DOWN-REGULATION.
RX MEDLINE=21560972; PubMed=11555652 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.M106033200;
RA Wallace A.D., Cidlowski J.A.;
RT "Proteasome-mediated glucocorticoid receptor degradation restricts
RT transcriptional signaling by glucocorticoids.";
RL J. Biol. Chem. 276:42714-42721(2001).
RN [10]
RP ALTERNATIVE INITIATION, AND MUTAGENESIS OF MET-1 AND MET-28.
RX MEDLINE=21329577; PubMed=11435610 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1210/me.15.7.1093;
RA Yudt M.R., Cidlowski J.A.;
RT "Molecular identification and characterization of A and B forms of the
RT glucocorticoid receptor.";
RL Mol. Endocrinol. 15:1093-1103(2001).
RN [11]
RP HETEROMULTIMERIC COMPLEX FORMATION, AND MECHANISM OF TRANSLOCATION TO
RP THE NUCLEUS.
RX MEDLINE=21826493; PubMed=11751894 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.C100531200;
RA Davies T.H., Ning Y.M., Sanchez E.R.;
RT "A new first step in activation of steroid receptors: hormone-induced
RT switching of FKBP51 and FKBP52 immunophilins.";
RL J. Biol. Chem. 277:4597-4600(2002).
CC -!- FUNCTION: Receptor for glucocorticoids (GC). Has a dual mode of
CC action: as a transcription factor that binds to glucocorticoid
CC response elements (GRE) and as a modulator of other transcription
CC factors. Affects inflammatory responses, cellular proliferation
CC and differentiation in target tissues.
CC -!- SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90, HSP70,
CC and FKBP5 or another immunophilin, or the immunophilin homolog
CC PPP5C. Upon ligand binding FKBP5 dissociates from the complex and
CC FKBP4 takes its place, thereby linking the complex to dynein and
CC mediating transport to the nucleus, where the complex dissociates.
CC Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the
CC retinoid X receptor. Binds STAT5A and STAT5B homodimers and
CC heterodimers. Interacts with NRIP1, TGFB1I1, POU2F1, POU2F2 and
CC TRIM28. Interacts with several coactivator complexes, including
CC the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160
CC coactivators such as NCOA2 and NCOA6. Interaction with BAG1
CC inhibits transactivation (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasmic in the absence of ligand;
CC nuclear after ligand-binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=1-A, GR form A;
CC IsoId=P06537-1; Sequence=Displayed;
CC Note=Isoform 1-B is produced by alternative initiation at Met-28
CC of isoform 1-A;
CC Name=2; Synonyms=2-A, GR form B;
CC IsoId=P06537-2; Sequence=VSP_003704;
CC Note=Isoform 2-B is produced by alternative initiation at Met-28
CC of isoform 2-A;
CC Event=Alternative initiation;
CC Comment=4 isoforms, 1-A (shown here), 1-B, 2-A and 2-B, are
CC produced by alternative initiation at Met-1 and Met-28;
CC -!- INDUCTION: Down-regulated by glucocorticoids.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain,
CC a DNA-binding domain and a C-terminal steroid-binding domain.
CC -!- PTM: Increased proteasome-mediated degradation in response to
CC glucocorticoids.
CC -!- PTM: Phosphorylated in the absence of hormone; becomes
CC hyperphosphorylated in the presence of glucocorticoids.
CC -!- PTM: Sumoylated; this reduces transcription transactivation (By
CC similarity).
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily.
CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
CC --------------------------------------------------------------------------
CC This Swiss-Prot entry is copyright. It is produced through a collaboration
CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
CC use as long as its content is in no way modified and this statement is not
CC removed.
CC --------------------------------------------------------------------------
DR EMBL; X04435; CAA28031.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X13358; CAA31738.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X13359; CAA31739.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PIR; A25691; A25691.
DR HSSP; P06536; 1GDC. [HSSP ENTRY / SWISS-3DIMAGE / PDB]
DR SMR; P06537; 424-498, 529-783.
DR IntAct; P06537; -.
DR TRANSFAC; T00335; -.
DR Ensembl; ENSMUSG00000024431; Mus_musculus
DR MGD; MGI:95824; Nr3c1.
DR GeneLynx; Nr3c1..
DR SOURCE; Nr3c1..
DR GO; GO:0005634; C:nucleus; IDA.
DR GO; GO:0005515; F:protein binding; IPI.
DR InterPro; IPR001409; Glcrtcd_receptor.
DR InterPro; IPR000536; Hrmon_recept_lig.
DR InterPro; IPR001723; Stdhrmn_receptor.
DR InterPro; IPR008946; Str_ncl_receptor.
DR InterPro; IPR001628; Znf_C4steroid.
DR InterPro; Graphical view of domain structure.
DR Pfam; PF02155; GCR; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR Pfam; Graphical view of domain structure.
DR PRINTS; PR00528; GLCORTICOIDR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR ProDom; PD000035; Znf_C4steroid; 1.
DR ProDom [Domain structure / List of seq. sharing at least 1 domain ]
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR CMR; P06537.
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; P06537.
DR ProtoNet; P06537.
DR ProtoMap; P06537.
DR PRESAGE; P06537.
DR DIP; P06537.
DR ModBase; P06537.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW Alternative initiation; Alternative splicing; DNA-binding;
KW Nuclear protein; Phosphorylation; Receptor; Steroid-binding;
KW Trans-acting factor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc-finger.
FT CHAIN 1 783 Glucocorticoid receptor, A-type isoforms.
FT CHAIN 28 783 Glucocorticoid receptor, B-type isoforms.
FT INIT_MET 28 28 For B-type isoforms.
FT DOMAIN 1 427 Modulating.
FT DOMAIN 407 426 Glu/Ser/Pro/Thr-rich (PEST region)
FT (Probable).
FT DNA_BIND 425 500 Nuclear receptor-type.
FT DNA_BIND 428 493 Nuclear receptor-type.
FT ZN_FING 428 448 C4-type.
FT ZN_FING 464 488 C4-type.
FT DOMAIN 494 534 Hinge.
FT DOMAIN 535 783 Steroid-binding.
FT DOMAIN 75 82 Poly-Gln.
FT MOD_RES 122 122 Phosphoserine.
FT MOD_RES 150 150 Phosphoserine.
FT MOD_RES 159 159 Phosphothreonine.
FT MOD_RES 212 212 Phosphoserine.
FT MOD_RES 220 220 Phosphoserine.
FT MOD_RES 234 234 Phosphoserine.
FT MOD_RES 315 315 Phosphoserine.
FT VARSPLIC 458 458 G -> GR (in isoform 2).
FT /FTId=VSP_003704.
FT MUTAGEN 1 1 M->T: Abolishes expression of A-type
FT isoforms.
FT MUTAGEN 28 28 M->T: Abolishes expression of B-type
FT isoforms. 1-B.
FT MUTAGEN 426 426 K->A: Abolishes glucocorticoid-mediated
FT degradation and enhances transcription
FT trans-activation.
FT CONFLICT 437 437 V -> G (in Ref. 2).
SQ SEQUENCE 783 AA; 86053 MW; 455E5C1C3C955F2A CRC64;
MDSKESLAPP GRDEVPSSLL GRGRGSVMDL YKTLRGGATV KVSASSPSVA AASQADSKQQ
RILLDFSKGS ASNAQQQQQQ QQPQPDLSKA VSLSMGLYMG ETETKVMGND LGYPQQGQLG
LSSGETDFRL LEESIANLNR STSRPENPKS STPAAGCATP TEKEFPQTHS DPSSEQQNRK
SQPGTNGGSV KLYTTDQSTF DILQDLEFSA GSPGKETNES PWRSDLLIDE NLLSPLAGED
DPFLLEGDVN EDCKPLILPD TKPKIQDTGD TILSSPSSVA LPQVKTEKDD FIELCTPGVI
KQEKLGPVYC QASFSGTNII GNKMSAISVH GVSTSGGQMY HYDMNTASLS QQQDQKPVFN
VIPPIPVGSE NWNRCQGSGE DNLTSLGAMN FAGRSVFSNG YSSPGMRPDV SSPPSSSSTA
TGPPPKLCLV CSDEASVCHY GVLTCGSCKV FFKRAVEGQH NYLCAGRNDC IIDKIRRKNC
PACRYRKCLQ AGMNLEARKT KKKIKGIQQA TAGVSQDTSE NANKTIVPAA LPQLTPTLVS
LLEVIEPEVL YAGYDSSVPD SAWRIMTTLN MLGGRQVIAA VKWAKAIPGF RNLHLDDQMT
LLQYSWMFLM AFALGWRSYR QASGNLLCFA PDLIINEQRM TLPCMYDQCK HMLFISTELQ
RLQVSYEEYL CMKTLLLLSS VPKEGLKSQE LFDEIRMTYI KELGKAIVKR EGNSSQNWQR
FYQLTKLLDS MHDVVENLLS YCFQTFLDKS MSIEFPEMLA EIITNQIPKY SNGNIKKLLF
HQK
//