P06536 · GCR_RAT
- ProteinGlucocorticoid receptor
- GeneNr3c1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids795 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (By similarity).
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 (By similarity).
In response to induction by transcription factor EGR1/NGFI-A in the hippocampus, may play a role in the behavioral and hypothalamic-pituitary-adrenal responses to stress in offspring (PubMed:15220929).
Isoform A
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 440-505 | Nuclear receptor | ||||
Sequence: CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRKCLQAGM |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlucocorticoid receptor
- Short namesGR
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP06536
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Isoform A
In the presence of NR1D1 shows a time-dependent subcellular localization, localizing to the cytoplasm at ZT8 and to the nucleus at ZT20 (By similarity).
Lacks this diurnal pattern of localization in the absence of NR1D1, localizing to both nucleus and the cytoplasm at ZT8 and ZT20 (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1 | Abolishes expression of A-type isoforms. | ||||
Sequence: M → T | ||||||
Mutagenesis | 28 | Abolishes expression of B-type isoforms. | ||||
Sequence: M → T | ||||||
Natural variant | 77 | in strain: Brown Norway/Crl | ||||
Sequence: Missing | ||||||
Natural variant | 78-79 | in strain: SHR/OlaIpcv | ||||
Sequence: Missing | ||||||
Natural variant | 83-96 | in strain: Sprague-Dawley | ||||
Sequence: Missing | ||||||
Natural variant | 226 | in strain: SHR/OlaIpcv and Brown Norway/Crl | ||||
Sequence: S → G | ||||||
Natural variant | 260 | in strain: SHR/OlaIpcv and Brown Norway/Crl | ||||
Sequence: N → D | ||||||
Mutagenesis | 297 | Enhances transcriptional activity; when associated with R-313. | ||||
Sequence: K → R | ||||||
Mutagenesis | 313 | Enhances transcriptional activity; when associated with R-297. | ||||
Sequence: K → R | ||||||
Mutagenesis | 481 | Disrupts dimerization and decreases transcription transactivation. | ||||
Sequence: D → R | ||||||
Mutagenesis | 488 | Loss of chromatin specific function and reduces chromatin remodeling. Abolishes interaction with SMARD1. | ||||
Sequence: R → Q | ||||||
Mutagenesis | 500 | Abolishes interaction with POU2F2. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 501 | Abrogates DNA-binding and transcription transactivation. Abolishes interaction with POU2F1 and POU2F2. | ||||
Sequence: L → P | ||||||
Mutagenesis | 656 | Strongly increases affinity for dexamethasone. | ||||
Sequence: C → S | ||||||
Mutagenesis | 721 | Abolishes the stimulatory effect of RWDD3 on its transcriptional activity. Diminishes NCOA2 coactivator activity. | ||||
Sequence: K → R | ||||||
Mutagenesis | 773 | Abolishes interaction with NCOA1 and reduces transcription transactivation; when associated with S-656. | ||||
Sequence: E → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 5 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000019941 | 1-795 | Glucocorticoid receptor | |||
Sequence: MDSKESLAPPGRDEVPGSLLGQGRGSVMDFYKSLRGGATVKVSASSPSVAAASQADSKQQRILLDFSKGSTSNVQQRQQQQQQQQQQQQQQQQQQQPDLSKAVSLSMGLYMGETETKVMGNDLGYPQQGQLGLSSGETDFRLLEESIANLNRSTSVPENPKSSTSATGCATPTEKEFPKTHSDASSEQQNRKSQTGTNGGSVKLYPTDQSTFDLLKDLEFSAGSPSKDTNESPWRSDLLIDENLLSPLAGEDDPFLLEGNTNEDCKPLILPDTKPKIKDTGDTILSSPSSVALPQVKTEKDDFIELCTPGVIKQEKLGPVYCQASFSGTNIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPVFNVIPPIPVGSENWNRCQGSGEDSLTSLGALNFPGRSVFSNGYSSPGMRPDVSSPPSSSSAATGPPPKLCLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRKCLQAGMNLEARKTKKKIKGIQQATAGVSQDTSENPNKTIVPAALPQLTPTLVSLLEVIEPEVLYAGYDSSVPDSAWRIMTTLNMLGGRQVIAAVKWAKAILGLRNLHLDDQMTLLQYSWMFLMAFALGWRSYRQSSGNLLCFAPDLIINEQRMSLPCMYDQCKHMLFVSSELQRLQVSYEEYLCMKTLLLLSSVPKEGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLTYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK | ||||||
Modified residue | 24 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 46 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 134 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 155 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 162 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 171 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 224 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 232 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 246 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 278 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 287 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 297 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 297 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 313 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 313 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Modified residue | 327 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 424 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 438 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 499 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 511 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 513 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 514 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 721 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K |
Post-translational modification
In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:21730050).
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 (By similarity).
Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity).
Directly interacts with UNC45A (By similarity).
Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor (By similarity).
Binds STAT5A and STAT5B homodimers and heterodimers (By similarity).
Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (PubMed:10364267, PubMed:10480874).
Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (PubMed:10866662, PubMed:9111344).
Interaction with BAG1 inhibits transactivation (By similarity).
Interacts with HEXIM1 and TGFB1I1 (By similarity).
Interacts with NCOA1 (PubMed:12917342).
Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (PubMed:12118039, PubMed:12917342).
Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (By similarity).
Interacts with CIART (By similarity).
Interacts with RWDD3 (PubMed:23508108).
Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (PubMed:23508108).
Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (By similarity).
Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (By similarity).
Interacts with GSK3B (By similarity).
Interacts with FNIP1 and FNIP2 (By similarity).
Interacts (via C-terminus) with HNRNPU (via C-terminus) (By similarity).
Interacts with MCM3AP (By similarity).
Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity).
In the absence of hormonal ligand, interacts with TACC1 (By similarity).
Interacts (via NR LBD domain) with ZNF764 (via KRAB domain); the interaction regulates transcription factor activity of NR3C1 by directing its actions toward certain biologic pathways (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P06536 | Mvp Q62667 | 2 | EBI-1187143, EBI-918333 | |
XENO | P06536 | NCOA1 Q15788 | 2 | EBI-1187143, EBI-455189 | |
BINARY | P06536 | Ntrk2 Q63604 | 2 | EBI-1187143, EBI-7287667 | |
XENO | P06536 | PAGR1 Q9BTK6 | 2 | EBI-1187143, EBI-2372223 | |
XENO | P06536 | SMARCA4 P51532 | 3 | EBI-1187143, EBI-302489 | |
XENO | P06536 | SMARCD1 Q96GM5 | 2 | EBI-1187143, EBI-358489 |
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region, compositional bias, zinc finger, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-24 | Disordered | ||||
Sequence: MDSKESLAPPGRDEVPGSLLGQGR | ||||||
Region | 1-439 | Modulating | ||||
Sequence: MDSKESLAPPGRDEVPGSLLGQGRGSVMDFYKSLRGGATVKVSASSPSVAAASQADSKQQRILLDFSKGSTSNVQQRQQQQQQQQQQQQQQQQQQQPDLSKAVSLSMGLYMGETETKVMGNDLGYPQQGQLGLSSGETDFRLLEESIANLNRSTSVPENPKSSTSATGCATPTEKEFPKTHSDASSEQQNRKSQTGTNGGSVKLYPTDQSTFDLLKDLEFSAGSPSKDTNESPWRSDLLIDENLLSPLAGEDDPFLLEGNTNEDCKPLILPDTKPKIKDTGDTILSSPSSVALPQVKTEKDDFIELCTPGVIKQEKLGPVYCQASFSGTNIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPVFNVIPPIPVGSENWNRCQGSGEDSLTSLGALNFPGRSVFSNGYSSPGMRPDVSSPPSSSSAATGPPPKL | ||||||
Compositional bias | 67-102 | Polar residues | ||||
Sequence: SKGSTSNVQQRQQQQQQQQQQQQQQQQQQQPDLSKA | ||||||
Region | 67-103 | Disordered | ||||
Sequence: SKGSTSNVQQRQQQQQQQQQQQQQQQQQQQPDLSKAV | ||||||
Compositional bias | 151-171 | Polar residues | ||||
Sequence: NRSTSVPENPKSSTSATGCAT | ||||||
Region | 151-206 | Disordered | ||||
Sequence: NRSTSVPENPKSSTSATGCATPTEKEFPKTHSDASSEQQNRKSQTGTNGGSVKLYP | ||||||
Compositional bias | 187-206 | Polar residues | ||||
Sequence: EQQNRKSQTGTNGGSVKLYP | ||||||
Zinc finger | 440-460 | NR C4-type | ||||
Sequence: CLVCSDEASGCHYGVLTCGSC | ||||||
Zinc finger | 476-500 | NR C4-type | ||||
Sequence: CAGRNDCIIDKIRRKNCPACRYRKC | ||||||
Region | 504-795 | Interaction with CLOCK | ||||
Sequence: GMNLEARKTKKKIKGIQQATAGVSQDTSENPNKTIVPAALPQLTPTLVSLLEVIEPEVLYAGYDSSVPDSAWRIMTTLNMLGGRQVIAAVKWAKAILGLRNLHLDDQMTLLQYSWMFLMAFALGWRSYRQSSGNLLCFAPDLIINEQRMSLPCMYDQCKHMLFVSSELQRLQVSYEEYLCMKTLLLLSSVPKEGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLTYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK | ||||||
Region | 506-541 | Hinge | ||||
Sequence: NLEARKTKKKIKGIQQATAGVSQDTSENPNKTIVPA | ||||||
Domain | 542-776 | NR LBD | ||||
Sequence: ALPQLTPTLVSLLEVIEPEVLYAGYDSSVPDSAWRIMTTLNMLGGRQVIAAVKWAKAILGLRNLHLDDQMTLLQYSWMFLMAFALGWRSYRQSSGNLLCFAPDLIINEQRMSLPCMYDQCKHMLFVSSELQRLQVSYEEYLCMKTLLLLSSVPKEGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLTYCFQTFLDKTMSIEFPEMLAEIIT | ||||||
Region | 550-715 | Interaction with CRY1 | ||||
Sequence: LVSLLEVIEPEVLYAGYDSSVPDSAWRIMTTLNMLGGRQVIAAVKWAKAILGLRNLHLDDQMTLLQYSWMFLMAFALGWRSYRQSSGNLLCFAPDLIINEQRMSLPCMYDQCKHMLFVSSELQRLQVSYEEYLCMKTLLLLSSVPKEGLKSQELFDEIRMTYIKEL |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative initiation.
P06536-1
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.
- NameA
- Length795
- Mass (Da)87,556
- Last updated1995-11-01 v2
- Checksum9C9DE0B1D6724845
P06536-2
- NameB
- Differences from canonical
- 1-27: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9PT44 | E9PT44_RAT | Nr3c1 | 795 | ||
A0A8I6A088 | A0A8I6A088_RAT | Nr3c1 | 414 |
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018969 | 1-27 | in isoform B | |||
Sequence: Missing | ||||||
Compositional bias | 67-102 | Polar residues | ||||
Sequence: SKGSTSNVQQRQQQQQQQQQQQQQQQQQQQPDLSKA | ||||||
Sequence conflict | 95-96 | in Ref. 3; AAL78956 | ||||
Sequence: Missing | ||||||
Sequence conflict | 98 | in Ref. 1; AAA41203 | ||||
Sequence: D → G | ||||||
Compositional bias | 151-171 | Polar residues | ||||
Sequence: NRSTSVPENPKSSTSATGCAT | ||||||
Compositional bias | 187-206 | Polar residues | ||||
Sequence: EQQNRKSQTGTNGGSVKLYP | ||||||
Sequence conflict | 345 | in Ref. 4; CAA68545 | ||||
Sequence: S → T | ||||||
Sequence conflict | 600 | in Ref. 2; CAA72938 and 3; AAL66772/AAL78956 | ||||
Sequence: L → P | ||||||
Sequence conflict | 602 | in Ref. 3; AAL66772/AAL78956 | ||||
Sequence: L → F |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M14053 EMBL· GenBank· DDBJ | AAA41203.1 EMBL· GenBank· DDBJ | mRNA | ||
Y12264 EMBL· GenBank· DDBJ | CAA72938.1 EMBL· GenBank· DDBJ | mRNA | ||
AY066016 EMBL· GenBank· DDBJ | AAL66772.2 EMBL· GenBank· DDBJ | mRNA | ||
AF455050 EMBL· GenBank· DDBJ | AAL78956.1 EMBL· GenBank· DDBJ | mRNA | ||
Y00489 EMBL· GenBank· DDBJ | CAA68545.1 EMBL· GenBank· DDBJ | mRNA | ||
X69666 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
X69667 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
X69668 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
X69669 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
X69670 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |