GCR_ONCMY
ID GCR_ONCMY Reviewed; 758 AA.
AC P49843;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 135.
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 Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Protacanthopterygii; Salmoniformes;
OC Salmonidae; Salmoninae; Oncorhynchus.
OX NCBI_TaxID=8022;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH
RP STEROIDS, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7649084; DOI=10.1210/endo.136.9.7649084;
RA Ducouret B., Tujague M., Ashraf J., Mouchel N., Servel N., Valotaire Y.,
RA Thompson E.B.;
RT "Cloning of a teleost fish glucocorticoid receptor shows that it contains a
RT deoxyribonucleic acid-binding domain different from that of mammals.";
RL Endocrinology 136:3774-3783(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Pituitary;
RX PubMed=8766708; DOI=10.1016/0014-5793(96)00596-0;
RA Takeo J., Hata J., Segawa C., Toyohara H., Yamashita S.;
RT "Fish glucocorticoid receptor with splicing variants in the DNA binding
RT domain.";
RL FEBS Lett. 389:244-248(1996).
CC -!- FUNCTION: Receptor for glucocorticoids (GC) (PubMed:7649084,
CC PubMed:8766708). Has a dual mode of action: as a transcription factor
CC that binds to glucocorticoid response elements (GRE), both for nuclear
CC and mitochondrial DNA, and as a modulator of other transcription
CC factors (By similarity). Affects inflammatory responses, cellular
CC proliferation and differentiation in target tissues (By similarity).
CC Involved in chromatin remodeling (By similarity). Plays a role in rapid
CC mRNA degradation by binding to the 5' UTR of target mRNAs and
CC interacting with PNRC2 in a ligand-dependent manner which recruits the
CC RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA
CC decay (By similarity). Could act as a coactivator for STAT5-dependent
CC transcription upon growth hormone (GH) stimulation and could reveal an
CC essential role of hepatic GR in the control of body growth (By
CC similarity). Mediates glucocorticoid-induced apoptosis (By similarity).
CC Promotes accurate chromosome segregation during mitosis (By
CC similarity). May act as a tumor suppressor (By similarity). May play a
CC negative role in adipogenesis through the regulation of lipolytic and
CC antilipogenic gene expression (By similarity).
CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537,
CC ECO:0000269|PubMed:7649084, ECO:0000269|PubMed:8766708}.
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. Directly interacts with UNC45A. Binds to DNA as a
CC homodimer, and as heterodimer with NR3C2 or the retinoid X receptor.
CC Binds STAT5A and STAT5B homodimers and heterodimers. Interacts with
CC NRIP1, POU2F1, POU2F2 and TRIM28. Interacts with several coactivator
CC complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada
CC complex) and p160 coactivators such as NCOA2 and NCOA6. Interaction
CC with BAG1 inhibits transactivation. Interacts with HEXIM1, PELP1 and
CC TGFB1I1. Interacts with NCOA1, NCOA3, SMARCA4, SMARCC1, SMARCD1, and
CC SMARCE1 (By similarity). {ECO:0000250}.
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. {ECO:0000250|UniProtKB:P04150}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49843-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49843-2; Sequence=VSP_012542;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in all tissues tested
CC including liver, gills, intestine, skeletal muscle, kidney, heart,
CC spleen, stomach, brain, pituitary, ovary, testis, skin and bladder.
CC Isoform 2 is found only in testis. {ECO:0000269|PubMed:7649084,
CC ECO:0000269|PubMed:8766708}.
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: Phosphorylated in the absence of hormone; becomes
CC hyperphosphorylated in the presence of glucocorticoids. May be
CC dephosphorylated by PPP5C, attenuates NR3C1 action (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
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DR EMBL; Z54210; CAA90937.1; -; mRNA.
DR PIR; S60586; S60586.
DR RefSeq; NP_001118202.1; NM_001124730.1. [P49843-1]
DR AlphaFoldDB; P49843; -.
DR SMR; P49843; -.
DR GeneID; 100136786; -.
DR KEGG; omy:100136786; -.
DR OrthoDB; 333292at2759; -.
DR GO; GO:1990794; C:basolateral part of cell; IDA:AgBase.
DR GO; GO:0005737; C:cytoplasm; IDA:AgBase.
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; IDA:AgBase.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:AgBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0098531; F:ligand-activated transcription factor activity; IDA:AgBase.
DR GO; GO:0031963; F:nuclear cortisol receptor activity; IDA:AgBase.
DR GO; GO:0004883; F:nuclear glucocorticoid receptor activity; IDA:AgBase.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IMP:AgBase.
DR GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR GO; GO:1990239; F:steroid hormone binding; IDA:AgBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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:0010628; P:positive regulation of gene expression; IDA:AgBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0046688; P:response to copper ion; IDA:AgBase.
DR GO; GO:0051414; P:response to cortisol; IDA:AgBase.
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; 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 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Cytoplasm; Cytoskeleton;
KW DNA-binding; Lipid-binding; Metal-binding; Mitochondrion; Nucleus;
KW Receptor; Steroid-binding; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..758
FT /note="Glucocorticoid receptor"
FT /id="PRO_0000053679"
FT DOMAIN 499..733
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 387..461
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 387..407
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 432..456
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..386
FT /note="Modulating"
FT REGION 1..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 462..498
FT /note="Hinge"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 417..425
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8766708"
FT /id="VSP_012542"
SQ SEQUENCE 758 AA; 83345 MW; 429CDCCBEB35DB5D CRC64;
MDPGGLKHSK DKGLAFGKLS ESSVEGSFSG DTGGSKSTTS TSLMHLPGSR PQPPARDSAN
GLNVTTTQME LSTGGLTIEE AEVKVMEKAI RMQQPQKPQQ NQQLFENFAL LEASIADLNR
SNTPGSSVLG RPHDLFSLKT ENFSPMDKDR LDMGSVSFGQ SQKDLDVNER LLGDNTMDIL
QDLDLPGSLS DLNEFYVSDE AAFLSSLSVE DVLLEDGNME TKPIDCSNGG NCTNVDSADQ
QKQLLEAGVS MPVIKTEEDA DTSFIQLCTP GVIKQENDRR SFCQISSLDL PSTHNSAGSI
SGPSYPYGAN TSTAVSLQQD QKPVFGLYPP LPSVSDSWNR GNGYATGSGM SSSSFPVGFS
SPKARPEASG SASSAPAKPS GPTHKICLVC SDEASGCHYG VLTCGSCKVF FKRAVEGWRA
RQNTDGQHNY LCAGRNDCII DKIRRKNCPA CRFRKCLQAG MNLEARKNKK LIRLKGQQTT
MEPNPPPPDE RACALIPKSM PQLVPTMLSL LKAIEPEAIY SGYDSTIPDT STRLMTTLNR
LGGQQVVSAV KWAKSLPGFR NLHLDDQMTL LQCSWLFLMS FGLGWRSYQQ CNGGMLCFAP
DLVINDERMK LPYMTDQCEQ MLKISTEFVR LQVSYDEYLC MKVLLLLSTV PKDGLKSQAV
FDEIRMTYIK ELGKAIVKRE ENSSQNWQRF YQLTKLLDSM QEMVGGLLQI CFYTFVNKSL
SVEFPEMLAE IISNQLPKFK DGSVKPLLFH ALNHDTMP
