GCR_PIG
ID GCR_PIG Reviewed; 782 AA.
AC Q9N1U3; P79405; Q5S4M0; Q9GKZ9;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Glucocorticoid receptor;
DE Short=GR;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 1;
GN Name=NR3C1; Synonyms=GRL;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16421205; DOI=10.1152/ajpcell.00468.2005;
RA Carlin R.W., Sedlacek R.L., Quesnell R.R., Pierucci-Alves F., Grieger D.M.,
RA Schultz B.D.;
RT "PVD9902, a porcine vas deferens epithelial cell line that exhibits
RT neurotransmitter-stimulated anion secretion and expresses numerous
RT HCO3- transporters.";
RL Am. J. Physiol. 290:C1560-C1571(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-744.
RC TISSUE=Liver;
RA Gutscher M., Eder S., Mueller M., Claus R.;
RT "Porcine glucocorticoid receptor -- sequencing, cloning, recombinant
RT expression and raising an antiserum.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 593-782.
RC STRAIN=Large white; TISSUE=Hippocampus;
RA Perreau V., Moisan M.P.;
RT "Sus scrofa glucocorticoid receptor partial cDNA (hormone binding
RT domain).";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for glucocorticoids (GC). Has a dual mode of action:
CC as a transcription factor that binds to glucocorticoid response
CC elements (GRE), both for nuclear and mitochondrial DNA, and as a
CC modulator of other transcription factors. Affects inflammatory
CC responses, cellular proliferation and differentiation in target
CC tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA
CC degradation by binding to the 5' UTR of target mRNAs and interacting
CC with PNRC2 in a ligand-dependent manner which recruits the RNA helicase
CC UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could
CC act as a coactivator for STAT5-dependent transcription upon growth
CC hormone (GH) stimulation and could reveal an essential role of hepatic
CC GR in the control of body growth. Mediates glucocorticoid-induced
CC apoptosis. Promotes accurate chromosome segregation during mitosis. May
CC act as a tumor suppressor. May play a negative role in adipogenesis
CC through the regulation of lipolytic and antilipogenic gene expression.
CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537}.
CC -!- SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90AA1,
CC HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1,
CC or the immunophilin homolog PPP5C. Upon ligand binding FKBP5
CC dissociates from the complex and FKBP4 takes its place, thereby linking
CC the complex to dynein and mediating transport to the nucleus, where the
CC complex dissociates. Probably forms a complex composed of chaperones
CC HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein
CC TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-
CC chaperones STIP1/HOP and PTGES3/p23. Directly interacts with UNC45A.
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, POU2F1, POU2F2 and TRIM28.
CC Interacts with several coactivator complexes, including the SMARCA4
CC complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such
CC as NCOA2 and NCOA6. Interaction with BAG1 inhibits transactivation.
CC Interacts with HEXIM1 and TGFB1I1. Interacts with NCOA1. Interacts with
CC NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1. Interacts with CLOCK,
CC CRY1 and CRY2 in a ligand-dependent fashion. Interacts with CIART.
CC Interacts with RWDD3. Interacts with UBE2I/UBC9 and this interaction is
CC enhanced in the presence of RWDD3. Interacts with GRIP1. Interacts with
CC NR4A3 (via nuclear receptor DNA-binding domain), represses
CC transcription activity of NR4A3 on the POMC promoter Nur response
CC element (NurRE). Directly interacts with PNRC2 to attract and form a
CC complex with UPF1 and DCP1A; the interaction leads to rapid mRNA
CC degradation. Interacts with GSK3B. Interacts with FNIP1 and FNIP2.
CC Interacts (via C-terminus) with HNRNPU (via C-terminus). Interacts with
CC MCM3AP (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and
CC HSP90AB1 (By similarity). In the absence of hormonal ligand, interacts
CC with TACC1 (By similarity). {ECO:0000250|UniProtKB:P04150,
CC ECO:0000250|UniProtKB:P06536, ECO:0000250|UniProtKB:P06537}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04150}. Nucleus
CC {ECO:0000250|UniProtKB:P04150}. Mitochondrion
CC {ECO:0000250|UniProtKB:P04150}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:P04150}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:P04150}.
CC Note=After ligand activation, translocates from the cytoplasm to the
CC nucleus (By similarity). In the presence of NR1D1 shows a time-
CC dependent subcellular localization, localizing to the cytoplasm at ZT8
CC and to the nucleus at ZT20 (By similarity). Lacks this diurnal pattern
CC of localization in the absence of NR1D1, localizing to both nucleus and
CC the cytoplasm at ZT8 and ZT20 (By similarity).
CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain. The ligand-
CC binding domain is required for correct chromosome segregation during
CC mitosis although ligand binding is not required.
CC {ECO:0000250|UniProtKB:P04150}.
CC -!- PTM: Acetylation by CLOCK reduces its binding to glucocorticoid
CC response elements and its transcriptional activity. {ECO:0000250}.
CC -!- PTM: Increased proteasome-mediated degradation in response to
CC glucocorticoids. {ECO:0000250|UniProtKB:P04150}.
CC -!- PTM: Phosphorylated in the absence of hormone; becomes
CC hyperphosphorylated in the presence of glucocorticoid. The Ser-208,
CC Ser-231 and Ser-410-phosphorylated forms are mainly cytoplasmic, and
CC the Ser-216-phosphorylated form is nuclear. Phosphorylation at Ser-216
CC increases transcriptional activity. Phosphorylation at Ser-208, Ser-231
CC and Ser-410 decreases signaling capacity. Phosphorylation at Ser-410
CC may protect from glucocorticoid-induced apoptosis. Phosphorylation at
CC Ser-208 and Ser-216 is not required in regulation of chromosome
CC segregation. May be dephosphorylated by PPP5C, attenuates NR3C1 action.
CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537}.
CC -!- PTM: Ubiquitinated; restricts glucocorticoid-mediated transcriptional
CC signaling. {ECO:0000250|UniProtKB:P06537}.
CC -!- PTM: Sumoylation at Lys-282 and Lys-298 negatively regulates its
CC transcriptional activity. Sumoylation at Lys-708 positively regulates
CC its transcriptional activity in the presence of RWDD3. Sumoylation at
CC Lys-282 and Lys-298 is dispensable whereas sumoylation at Lys-708 is
CC critical for the stimulatory effect of RWDD3 on its transcriptional
CC activity. Heat shock increases sumoylation in a RWDD3-dependent manner.
CC {ECO:0000250|UniProtKB:P06536}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
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DR EMBL; AY779185; AAV66324.1; -; mRNA.
DR EMBL; AF141371; AAF66595.1; -; mRNA.
DR EMBL; AJ296022; CAC10271.1; -; mRNA.
DR EMBL; U88894; AAB53274.1; -; mRNA.
DR RefSeq; NP_001008481.1; NM_001008481.1.
DR AlphaFoldDB; Q9N1U3; -.
DR SMR; Q9N1U3; -.
DR STRING; 9823.ENSSSCP00000015324; -.
DR BindingDB; Q9N1U3; -.
DR ChEMBL; CHEMBL4295956; -.
DR PaxDb; Q9N1U3; -.
DR PeptideAtlas; Q9N1U3; -.
DR GeneID; 396740; -.
DR KEGG; ssc:396740; -.
DR CTD; 2908; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q9N1U3; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0004883; F:nuclear glucocorticoid receptor activity; IEA:InterPro.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR GO; GO:1990239; F:steroid hormone binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISS:UniProtKB.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR001409; Glcrtcd_rcpt.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF02155; GCR; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00528; GLCORTICOIDR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Chromatin regulator; Cytoplasm; Cytoskeleton; DNA-binding;
KW Isopeptide bond; Lipid-binding; Metal-binding; Methylation; Mitochondrion;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Steroid-binding;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..782
FT /note="Glucocorticoid receptor"
FT /id="PRO_0000053671"
FT DOMAIN 529..763
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 426..491
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 426..446
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 462..486
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..425
FT /note="Modulating"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 48..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..782
FT /note="Interaction with CLOCK"
FT /evidence="ECO:0000250"
FT REGION 492..528
FT /note="Hinge"
FT REGION 537..702
FT /note="Interaction with CRY1"
FT /evidence="ECO:0000250"
FT COMPBIAS 167..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 8
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 24
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P06537"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06537"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06537"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06537"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 485
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 497
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 499
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 500
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 263
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 282
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 282
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 298
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 298
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 424
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P06537"
FT CROSSLNK 708
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CONFLICT 45
FT /note="A -> S (in Ref. 2; AAF66595/CAC10271)"
FT /evidence="ECO:0000305"
FT CONFLICT 610
FT /note="V -> A (in Ref. 3; AAB53274)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 782 AA; 85640 MW; D006A0937EF34F85 CRC64;
MDPKESLTPP SREEIPSSVL GRERAHVMDF YKSLRGGTPV KVSAASPSLA AVSQPDSKQQ
RLAVDFPKGS GSNAQQPDLS KAVSLSMGLY MGETETKVMG SDLGFPQQGQ ISLSSGETDF
RLLEESIANL SRSTSVPENP KSSASAAGPA APAEKAFPKT HSDGAPEQPN VKGQTGTNGG
NVKLFTTDQS TFDIWRKKLQ DLELPSGSPG KETSESPWSS DLLIDENCLL SPLAGEEDPF
LLEGSSTEDC KPLVLPDTKP KVKDNGELIL PSPNSVPLPQ VKTEKEDFIE LCTPGVIKQE
KLGPAYCQAS FSGANIIGGK MSAISVHGVS TSGGQLYHYD MNTAASLSKQ QEQKPLFNVI
PPIPVGSENW NRCQGSGDDN LTSLGTLNFS GRSVFSNGYS SPGMRPDVSS PPSSSSAATG
PPPKLCLVCS DEASGCHYGV LTCGSCKVFF KRAVEGQHNY LCAGRNDCII DKIRRKNCPA
CRYRKCLQAG MNLEARKTKK KIKGIQQATT GVSQETSENS ANKTIVPATL PQLTPTLVSL
LEVIEPEVLY AGYDSSIPDS TWRIMTALNM LGGRQVIAAV KWAKAIPGFR NLHLDDQMTL
LQYSWMFLMV FALGWRSYRQ SSASLLCFAP DLVINEQRMA LPCMYDQCRH MLYVSSELQR
LQVSYEEYLC MKTLLLLSSV PKDGLKSQEL FDEIRMTYIK ELGKAIVKRE GNSSQNWQRF
YQLTKLLDSM HDVVENLLNY CFQTFLDKTM SIEFPEMLAE IITNQLPKYS SGNIKKLLFH
QK
