Swiss-Prot entry
ID GCR_RAT STANDARD; PRT; 795 AA.
AC P06536; O08624; Q8R463; Q8R5J0;
DT 01-JAN-1988 (Rel. 06, Created)
DT 01-NOV-1995 (Rel. 32, Last sequence update)
DT 01-MAY-2005 (Rel. 47, Last annotation update)
DE Glucocorticoid receptor (GR).
GN Name=Nr3c1; Synonyms=Grl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muridae; Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Hepatoma;
RX MEDLINE=86272086; PubMed=3755378 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1016/0092-8674(86)90659-8;
RA Miesfeld R., Rusconi S., Godowski P.J., Maler B.A., Okret S.,
RA Wikstroem A.-C., Gustafsson J.-A., Yamamoto K.R.;
RT "Genetic complementation of a glucocorticoid receptor deficiency by
RT expression of cloned receptor cDNA.";
RL Cell 46:389-399(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RA Heeley R.P., Gill E., van Zutphen B.;
RT "CAG repeat variation in the gene for rat glucocorticoid receptor: a
RT study of allele frequencies in inbred and wild rat populations and of
RT the steroid-binding properties of their polypeptides in vitro.";
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE, AND VARIANTS GLY-226 AND ASP-260.
RC STRAIN=Brown Norway/Crl, and SHR/OlaIpcv;
RA Pravenec M., Zidek V., Kostka V., Mlejnek P., Musilova A., Kren V.,
RA Jansa P., Forejt J., Lezin E.S., Kurtz T.W.;
RT "Genetic isolation of a QTL on chromosome 18 associated with salt
RT sensitivity in spontaneously hypertensive rats.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE OF 1-515.
RC STRAIN=Sprague-Dawley; TISSUE=Prostate;
RX MEDLINE=88067783; PubMed=3684608 [NCBI, ExPASy, EBI, Israel, Japan];
RA Chang C., Kokontis J., Chang C.T., Liao S.;
RT "Cloning and sequence analysis of the rat ventral prostate
RT glucocorticoid receptor cDNA.";
RL Nucleic Acids Res. 15:9603-9603(1987).
RN [5]
RP MUTAGENESIS OF ZINC FINGER.
RX MEDLINE=89052664; PubMed=3191912 [NCBI, ExPASy, EBI, Israel, Japan];
RA Severne Y., Wieland S., Schaffner W., Rusconi S.;
RT "Metal binding 'finger' structures in the glucocorticoid receptor
RT defined by site-directed mutagenesis.";
RL EMBO J. 7:2503-2508(1988).
RN [6]
RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION.
RX MEDLINE=89112207; PubMed=3216865 [NCBI, ExPASy, EBI, Israel, Japan];
RA Dong Y., Poellinger L., Gustafsson J.-A., Okret S.;
RT "Regulation of glucocorticoid receptor expression: evidence for
RT transcriptional and posttranslational mechanisms.";
RL Mol. Endocrinol. 2:1256-1264(1988).
RN [7]
RP MUTAGENESIS OF CYS-656.
RX MEDLINE=92042128; PubMed=1939229 [NCBI, ExPASy, EBI, Israel, Japan];
RA Chakraborti P.K., Garabedian M.J., Yamamoto K.R., Simons S.S. Jr.;
RT "Creation of 'super' glucocorticoid receptors by point mutations in
RT the steroid binding domain.";
RL J. Biol. Chem. 266:22075-22078(1991).
RN [8]
RP MUTAGENESIS OF ZINC FINGER.
RX MEDLINE=93195921; PubMed=8450530 [NCBI, ExPASy, EBI, Israel, Japan];
RA Zandi E., Galli I., Doebbeling U., Rusconi S.;
RT "Zinc finger mutations that alter domain interactions in the
RT glucocorticoid receptor.";
RL J. Mol. Biol. 230:124-136(1993).
RN [9]
RP REVIEW ON MUTAGENESIS.
RX MEDLINE=94249031; PubMed=8191545 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1016/0039-128X(94)90093-0;
RA Lanz R.B., Hug M., Gola M., Tallone T., Wieland S., Rusconi S.;
RT "Active, interactive, and inactive steroid receptor mutants.";
RL Steroids 59:148-152(1994).
RN [10]
RP HOMODIMERIZATION, HETERODIMERIZATION WITH NR3C2, AND MUTAGENESIS OF
RP ASP-481.
RX MEDLINE=96109290; PubMed=8618925 [NCBI, ExPASy, EBI, Israel, Japan];
RA Liu W., Wang J., Sauter N.K., Pearce D.;
RT "Steroid receptor heterodimerization demonstrated in vitro and in
RT vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:12480-12484(1995).
RN [11]
RP INTERACTION WITH NCOA2.
RX MEDLINE=97265407; PubMed=9111344 [NCBI, ExPASy, EBI, Israel, Japan];
RA Hong H., Kohli K., Garabedian M.J., Stallcup M.R.;
RT "GRIP1, a transcriptional coactivator for the AF-2 transactivation
RT domain of steroid, thyroid, retinoid, and vitamin D receptors.";
RL Mol. Cell. Biol. 17:2735-2744(1997).
RN [12]
RP PHOSPHORYLATION SITES THR-171; SER-224; SER-232 AND SER-246.
RX MEDLINE=98269094; PubMed=9603939 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.273.23.14315;
RA Rogatsky I., Waase C.L.M., Garabedian M.J.;
RT "Phosphorylation and inhibition of rat glucocorticoid receptor
RT transcriptional activation by glycogen synthase kinase-3 (GSK-3).
RT Species-specific differences between human and rat glucocorticoid
RT receptor signaling as revealed through GSK-3 phosphorylation.";
RL J. Biol. Chem. 273:14315-14321(1998).
RN [13]
RP INTERACTION WITH NRIP1.
RX MEDLINE=99292791; PubMed=10364267 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.274.25.18121;
RA Subramaniam N., Treuter E., Okret S.;
RT "Receptor interacting protein RIP140 inhibits both positive and
RT negative gene regulation by glucocorticoids.";
RL J. Biol. Chem. 274:18121-18127(1999).
RN [14]
RP INTERACTION WITH POU2F1 AND POU2F2, AND MUTAGENESIS OF CYS-500 AND
RP LEU-501.
RX MEDLINE=99410400; PubMed=10480874 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.274.38.26713;
RA Prefontaine G.G., Walther R., Giffin W., Lemieux M.E., Pope L.,
RA Hache R.J.G.;
RT "Selective binding of steroid hormone receptors to octamer
RT transcription factors determines transcriptional synergism at the
RT mouse mammary tumor virus promoter.";
RL J. Biol. Chem. 274:26713-26719(1999).
RN [15]
RP INTERACTION WITH NCOA6.
RX MEDLINE=20325329; PubMed=10866662 [NCBI, ExPASy, EBI, Israel, Japan];
RX DOI=10.1128/MCB.20.14.5048-5063.2000;
RA Mahajan M.A., Samuels H.H.;
RT "A new family of nuclear receptor coregulators that integrates nuclear
RT receptor signaling through CBP.";
RL Mol. Cell. Biol. 20:5048-5063(2000).
RN [16]
RP HOMODIMERIZATION, HETERODIMERIZATION WITH NR3C2, AND MUTAGENESIS OF
RP LEU-501.
RX MEDLINE=21216736; PubMed=11278286 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.M005363200;
RA Ou X.-M., Storring J.M., Kushwaha N., Albert P.R.;
RT "Heterodimerization of mineralocorticoid and glucocorticoid receptors
RT at a novel negative response element of the 5-HT1A receptor gene.";
RL J. Biol. Chem. 276:14299-14307(2001).
RN [17]
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 [18]
RP INTERACTION WITH NCOA1, AND MUTAGENESIS OF GLU-773.
RX MEDLINE=22113105; PubMed=12118039 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.M204013200;
RA Kucera T., Waltner-Law M., Scott D.K., Prasad R., Granner D.K.;
RT "A point mutation of the AF2 transactivation domain of the
RT glucocorticoid receptor disrupts its interaction with steroid receptor
RT coactivator 1.";
RL J. Biol. Chem. 277:26098-26102(2002).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 434-525.
RX MEDLINE=91326070; PubMed=1865905 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1038/352497a0;
RA Luisi B.F., Xu W.X., Otwinowski Z., Freedman L.P., Yamamoto K.R.,
RA Sigler P.B.;
RT "Crystallographic analysis of the interaction of the glucocorticoid
RT receptor with DNA.";
RL Nature 352:497-505(1991).
RN [20]
RP STRUCTURE BY NMR OF 440-510.
RX MEDLINE=90319784; PubMed=2115209 [NCBI, ExPASy, EBI, Israel, Japan];
RA Haerd T., Kellenbach E., Boelens R., Maler B.A., Dahlman K.,
RA Freedman L.P., Carlstedt-Duke J., Yamamoto K.R., Gustafsson J.-A.,
RA Kaptein R.;
RT "Solution structure of the glucocorticoid receptor DNA-binding
RT domain.";
RL Science 249:157-160(1990).
RN [21]
RP STRUCTURE BY NMR OF 440-525.
RX MEDLINE=92089066; PubMed=1751485 [NCBI, ExPASy, EBI, Israel, Japan];
RA Remerowski M.L., Kellenbach E., Boelens R., van der Marel A.,
RA van Boom J.H., Maler B.A., Yamamoto K.R., Kaptein R.;
RT "1H NMR studies of DNA recognition by the glucocorticoid receptor:
RT complex of the DNA binding domain with a half-site response element.";
RL Biochemistry 30:11620-11624(1991).
RN [22]
RP STRUCTURE BY NMR OF 440-525.
RX MEDLINE=92038072; PubMed=1936288 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1016/0014-5793(91)81322-Y;
RA Kellenbach E., Maler B.A., Yamamoto K.R., Boelens R., Kaptein R.;
RT "Identification of the metal coordinating residues in the DNA binding
RT domain of the glucocorticoid receptor by 113Cd-1H heteronuclear NMR
RT spectroscopy.";
RL FEBS Lett. 291:367-370(1991).
RN [23]
RP STRUCTURE BY NMR OF 439-510.
RX MEDLINE=94079877; PubMed=8257681 [NCBI, ExPASy, EBI, Israel, Japan];
RA Baumann H., Paulsen K., Kovacs H., Berglund H., Wright A.P.H.,
RA Gustafsson J.-A., Haerd T.;
RT "Refined solution structure of the glucocorticoid receptor DNA-binding
RT domain.";
RL Biochemistry 32:13463-13471(1993).
RN [24]
RP POLYMORPHISM OF POLY-GLN REGION.
RX MEDLINE=93261843; PubMed=8493115 [NCBI, ExPASy, EBI, Israel, Japan];
RA Gearing K.L., Gustafsson J.-A., Okret S.;
RT "Heterogeneity in the polyglutamine tract of the glucocorticoid
RT receptor from different rat strains.";
RL Nucleic Acids Res. 21:2014-2014(1993).
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 (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation;
CC Comment=2 isoforms, A (shown here) and B, are produced by
CC alternative initiation at Met-1 and Met-27;
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; M14053; AAA41203.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; Y12264; CAA72938.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AY066016; AAL66772.2; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AF455050; AAL78956.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; Y00489; CAA68545.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X69666; -; NOT_ANNOTATED_CDS. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X69667; -; NOT_ANNOTATED_CDS. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X69668; -; NOT_ANNOTATED_CDS. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X69669; -; NOT_ANNOTATED_CDS. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X69670; -; NOT_ANNOTATED_CDS. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PIR; A24194; QRRTG.
DR PDB; 1GDC; NMR; @=439-510. [ExPASy / RCSB]
DR PDB; 1GLU; X-ray; A/B=434-514. [ExPASy / RCSB]
DR PDB; 1LAT; X-ray; A/B=434-515. [ExPASy / RCSB]
DR PDB; 1R4O; X-ray; A/B=434-525. [ExPASy / RCSB]
DR PDB; 1R4R; X-ray; A/B=434-525. [ExPASy / RCSB]
DR PDB; 1RGD; NMR; @=440-510. [ExPASy / RCSB]
DR PDB; 2GDA; NMR; @=439-510. [ExPASy / RCSB]
DR SMR; P06536; 541-795.
DR TRANSFAC; T00333; -.
DR Ensembl; ENSRNOG00000014096; Rattus_norvegicus
DR RGD; 2741; Nr3c1.
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; P06536.
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; P06536.
DR ProtoNet; P06536.
DR ProtoMap; P06536.
DR PRESAGE; P06536.
DR DIP; P06536.
DR ModBase; P06536.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW 3D-structure; Alternative initiation; DNA-binding; Nuclear protein;
KW Phosphorylation; Polymorphism; Receptor; Steroid-binding;
KW Trans-acting factor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc-finger.
FT CHAIN 1 795 Glucocorticoid receptor, A-type isoforms.
FT CHAIN 28 795 Glucocorticoid receptor, B-type isoforms.
FT INIT_MET 28 28 For B-type isoforms.
FT DOMAIN 1 439 Modulating.
FT DOMAIN 419 438 Glu/Ser/Pro/Thr-rich (PEST region)
FT (Potential).
FT DNA_BIND 440 505 Nuclear receptor-type.
FT ZN_FING 440 460 C4-type.
FT ZN_FING 476 500 C4-type.
FT DOMAIN 506 546 Hinge.
FT DOMAIN 547 795 Steroid-binding.
FT DOMAIN 75 97 Poly-Gln.
FT MOD_RES 134 134 Phosphoserine (By similarity).
FT MOD_RES 171 171 Phosphothreonine.
FT MOD_RES 162 162 Phosphoserine (By similarity).
FT MOD_RES 224 224 Phosphoserine.
FT MOD_RES 232 232 Phosphoserine.
FT MOD_RES 246 246 Phosphoserine.
FT MOD_RES 327 327 Phosphoserine (By similarity).
FT VARIANT 77 77 Missing (in strain Brown Norway/Crl).
FT VARIANT 78 79 Missing (in strain SHR/OlaIpcv).
FT VARIANT 83 96 Missing (in strain Sprague-Dawley).
FT VARIANT 226 226 S -> G (in strain SHR/OlaIpcv and strain
FT Brown Norway/Crl).
FT VARIANT 260 260 N -> D (in strain SHR/OlaIpcv and strain
FT Brown Norway/Crl).
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.
FT MUTAGEN 481 481 D->R: Disrupts dimerization and decreases
FT transcription transactivation.
FT MUTAGEN 500 500 C->Y: Abolishes interaction with POU2F2.
FT MUTAGEN 501 501 L->P: Abrogates DNA-binding and
FT transcription transactivation. Abolishes
FT interaction with POU2F1 and POU2F2.
FT MUTAGEN 656 656 C->S: Strongly increases affinity for
FT dexamethasone.
FT MUTAGEN 773 773 E->A: Abolishes interaction with NCOA1
FT and reduces transcription
FT transactivation; when associated with S-
FT 656.
FT CONFLICT 98 98 D -> G (in Ref. 1).
FT CONFLICT 345 345 S -> T (in Ref. 4).
FT CONFLICT 600 600 L -> P (in Ref. 2 and 3).
FT CONFLICT 602 602 L -> F (in Ref. 3).
FT STRAND 439 439
FT TURN 441 443
FT STRAND 446 446
FT STRAND 449 450
FT STRAND 455 456
FT HELIX 458 469
FT TURN 486 487
FT HELIX 488 490
FT TURN 491 491
FT HELIX 493 503
FT TURN 504 504
SQ SEQUENCE 795 AA; 87556 MW; 9C9DE0B1D6724845 CRC64;
MDSKESLAPP GRDEVPGSLL GQGRGSVMDF YKSLRGGATV KVSASSPSVA AASQADSKQQ
RILLDFSKGS TSNVQQRQQQ QQQQQQQQQQ QQQQQQPDLS KAVSLSMGLY MGETETKVMG
NDLGYPQQGQ LGLSSGETDF RLLEESIANL NRSTSVPENP KSSTSATGCA TPTEKEFPKT
HSDASSEQQN RKSQTGTNGG SVKLYPTDQS TFDLLKDLEF SAGSPSKDTN ESPWRSDLLI
DENLLSPLAG EDDPFLLEGN TNEDCKPLIL PDTKPKIKDT GDTILSSPSS VALPQVKTEK
DDFIELCTPG VIKQEKLGPV YCQASFSGTN IIGNKMSAIS VHGVSTSGGQ MYHYDMNTAS
LSQQQDQKPV FNVIPPIPVG SENWNRCQGS GEDSLTSLGA LNFPGRSVFS NGYSSPGMRP
DVSSPPSSSS AATGPPPKLC LVCSDEASGC HYGVLTCGSC KVFFKRAVEG QHNYLCAGRN
DCIIDKIRRK NCPACRYRKC LQAGMNLEAR KTKKKIKGIQ QATAGVSQDT SENPNKTIVP
AALPQLTPTL VSLLEVIEPE VLYAGYDSSV PDSAWRIMTT LNMLGGRQVI AAVKWAKAIL
GLRNLHLDDQ MTLLQYSWMF LMAFALGWRS YRQSSGNLLC FAPDLIINEQ RMSLPCMYDQ
CKHMLFVSSE LQRLQVSYEE YLCMKTLLLL SSVPKEGLKS QELFDEIRMT YIKELGKAIV
KREGNSSQNW QRFYQLTKLL DSMHEVVENL LTYCFQTFLD KTMSIEFPEM LAEIITNQIP
KYSNGNIKKL LFHQK
//