Traditionally, once GR is bound by glucocorticoid, it translocates to the nucleus and functions as a transcription activator or suppressor for glucocorticoid-responsive genes ( 5 ). Endocrinol. Res. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Glucocorticoids and estrogens are two classes of steroid hormones that have essential but distinct physiologic functions. Although binding studies have suggested that glial cells may also express receptors, the expression of these receptors in specific classes of glia has not been studied previously.
Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.
Looking for abbreviations of GR II? Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity. U.S.A. 98:6865-6870(2001), Proc. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Strongly reduces sumoylation. Abolishes expression of D-type isoforms; when associated with I-316 and I-336. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.,This subsection of the Names and taxonomy section provides information on the name(s) of the organism that is the source of the protein sequence.
,This subsection of the Names and taxonomy section shows the unique identifier assigned by the NCBI to the source organism of the protein.
, Manual assertion inferred from combination of experimental and computational evidence,This subsection of the PTM / Processing section describes covalent linkages of various types formed between two proteins (interchain cross-links) or between two parts of the same protein (intrachain cross-links), except the disulfide bonds that are annotated in the 'Disulfide bond' subsection.
, Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2), Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate, Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate, Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin), Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO),This subsection of the PTM/processing section describes post-translational modifications (PTMs). Natl. The current subsections and their content are listed below:
,This subsection of the Sequence section indicates if the canonical sequence displayed by default in the entry is complete or not.
,This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). in GCCR; unknown pathological significance; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed: Can up- or down-modulate aggregation and nuclear localization of expanded polyglutamine polypeptides derived from AR and HD through specific regulation of gene expression. Microtubule-associated protein 1B (MAP1B) is present in glial cells phosphorylated different than in neurones.
More information in the GO evidence code guide
,Inferred from Physical Interaction
Acad. It is updated at every UniProt release.,This section provides information on the tertiary and secondary structure of a protein.
,This subsection of the 'Structure' section is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. It also includes information pertinent to the sequence(s), including length and molecular weight. COVID-19 is an emerging, rapidly evolving situation. RNAct, Protein-RNA interaction predictions for model organisms. Glucocorticoid receptor is a modular protein, meaning that they have distinct domains: (1) the amino-terminal A/B region, also called immunogenic, functional, or N-terminal domain (NTD), and (2) the C, D, and E regions also known as structural domain, comprising the DNA-binding domain (DBD), the hinge region, and the ligand-binding domain (LBD), respectively. Manual assertion according to rulesi, Pathway Commons web resource for biological pathway data, Reactome - a knowledgebase of biological pathways and processes, SignaLink: a signaling pathway resource with multi-layered regulatory networks, Online Mendelian Inheritance in Man (OMIM), neXtProt; the human protein knowledge platform, Eukaryotic Pathogen, Vector and Host Database Resources, Orphanet; a database dedicated to information on rare diseases and orphan drugs, The Pharmacogenetics and Pharmacogenomics Knowledge Base, Pharos NIH Druggable Genome Knowledgebase, ChEMBL database of bioactive drug-like small molecules, BioMuta curated single-nucleotide variation and disease association database, Domain mapping of disease mutations (DMDM),
Manually validated information inferred from a combination of experimental and computational evidence.
381:671-675(2009), Biochim. in GCCR; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. A prominent doublet at 90/92 kilodaltons was observed ⦠Almost complete loss of sumoylation; when associated with R-277. The glucocorticoid receptor is a specific type of receptor found within the cells of the body that specific hormones can bind to in order to perform their function. GRα, the classic glucocorticoid receptor, is expressed virtually in all organs and tissues and mediates most of the known actions of glucocorticoids. The endogenous glucocorticoid hormone cortisol diffuses through the cell membrane into the cytoplasmand binds to the glucocorticoid receptor (GR) resulting in release of the heat shock proteins. Decreases transactivation by dexamethasone by 95%. Lacks this diurnal pattern of localization in the absence of NR1D1, localizing to both nucleus and the cytoplasm at ZT8 and ZT20 (By similarity). 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). Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)). Acta 1813:1814-1821(2011), Proc. Natl. in GCCR; decreased DNA-binding and transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type. The glucocorticoid receptor (GR) is a master gene orchestrating the activation of gluconeogenic genes in the liver in response to food withdrawal. Furthermore, cells grown in the absence of glucocorticoids had diffuse GR staining over the cytoplasm, whereas cells grown in the presence of the synthetic glucocorticoid dexamethasone had strong nuclear staining. Endocrinol. Receptor for glucocorticoids (GC) (PubMed:Manually curated information which has been propagated from a related experimentally characterized protein.
The algorithm is described in the ISO 3309 standard. 87:1805-1809(2002), Isoform Alpha-B of Glucocorticoid receptor, Isoform Alpha-D3 of Glucocorticoid receptor, Isoform Alpha-D2 of Glucocorticoid receptor, Isoform Alpha-D1 of Glucocorticoid receptor, Isoform Beta-B of Glucocorticoid receptor, Isoform Beta-2 of Glucocorticoid receptor, Isoform GR-A beta of Glucocorticoid receptor, Human variants curated from literature reports. . Abolishes phosphorylation and enhances transcriptional activation. These elements correspond to the DSSP secondary structure code 'T'.,This subsection of the 'Structure' section is used to indicate the positions of experimentally determined beta strands within the protein sequence.
,This subsection of the 'Structure' section is used to indicate the positions of experimentally determined helical regions within the protein sequence.
,This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.
,This subsection of the Family and Domains section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.
,This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.
, Required for high transcriptional activity of isoform,This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.
,This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The sequence of this isoform differs from the canonical sequence as follows: 1-26: Missing. 55:363-371(2001), J. Clin. U.S.A. 112:E1540-E1549(2015), Biochem. The glucocorticoid receptor is an evolutionarily conserved transcription factor found in such diverse species as Xenopus, trout, rat, and human. Strongly reduces sumoylation. Accessibility Reduces activation mediated by ligand binding domain; when associated with A-585. Endocrinol. Endocrinol. We also present evidence sug- gesting that the nt' receptor is not produced as a large precur- It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Glucocorticoid Receptors of Type II listed as GR II Increases cell death. Natl.
This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). Prevention and treatment information (HHS). Enhances transactivation activity; does not affect transrepression activity; may increase sensitivity to exogenously administered glucocorticoids; may contribute to central obesity in men and show lack of association with other risk factors for coronary heart disease and diabetes mellitus. Epub 2017 Aug 8. Related terms: Hippocampus; Eicosanoid Receptor; Corticotropin-Releasing Hormone; Cortisol; Corticosterone Biophys. These receptors are key factors in determining individual sensitivity to glucocorticoids. Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (PubMed:25775514). Manual assertion based on opinion ini, DNA Data Bank of Japan; a nucleotide sequence database, Protein sequence database of the Protein Information Resource, Ensembl eukaryotic genome annotation project, Database of genes from NCBI RefSeq genomes, KEGG: Kyoto Encyclopedia of Genes and Genomes, Antibodypedia a portal for validated antibodies, GeneCards: human genes, protein and diseases, BioGRID ORCS database of CRISPR phenotype screens, ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data, The Gene Wiki collection of pages on human genes and proteins, Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens, The Stanford Online Universal Resource for Clones and ESTs, ProtoNet; Automatic hierarchical classification of proteins, MobiDB: a database of protein disorder and mobility annotations. Alex Said. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-480; A-492 and A-495. Metab.
More information in the GO evidence code guide
,Inferred from Biological aspect of Ancestor
In the absence of hormone, the glucocorticoid receptor (GR) resides in the cytosol complexed with a variety of proteins including heat shock protein 90 (hsp90), the heat shock protein 70 (hsp70) and the protein FKBP4 (FK506-binding protein 4). After a hormone binds to the corresponding receptor, the newly formed complex translocates itself into the cell nucleus, where it binds to glucocorticoid response elements in the promoter region of the target genes resulting in the regulation of gene expression. This section is only present in reviewed entries, i.e. GR II - Glucocorticoid Receptors of Type II.The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64)
More information in the GO evidence code guide
,Traceable Author Statement
Glucocorticoid-Induced Reductions of Myelination and Connexin 43 in Mixed Central Nervous System Cell Cultures Are Prevented by Mifepristone. Glia. This immunocytochemical study was undertaken to determine which of the different classes of glial cells express type II GR. Interaction with BAG1 inhibits transactivation (PubMed:10477749). We have isolated Chinese hamster ovary (CHO) cell lines expressing elevated levels of wild-type (W) and mutant forms of the glucocorticoid receptor (GR) using the technique of coamplification with a selectable dihydrofolate reductase (dhfr) cDNA. Decrease in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-494. 2019 Jan-Dec;15:1744806919850383. doi: 10.1177/1744806919850383. an experiment that has been published in the scientific literature, an orthologous protein, a record from another database, etc. Miguel-Hidalgo JJ, Carter K, Deloach PH, Sanders L, Pang Y. Neuroscience. Commun. The resulting activated form GR has two principal mechanisms of ac⦠Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (By similarity). is extremely low. Primary cultures of mixed glial cells from rat cerebrum and cerebellum, purified oligodendrocytes and astrocytes, as well as two glial tumor cell lines were screened for the expression of glucocorticoid receptors using a mouse monoclonal antibody directed against rat liver GR (BuGR-2). It has been suggested that glucocorticoids can attenuate estrogen responses, but the mechanism by which glucocorticoids inhibit estrogenic activity is unknown. Directly interacts with UNC45A (PubMed:16478993). Res. Sequence conflicts are usually of unknown origin.,This subsection of the 'Sequence' section provides information on polymorphic variants. Reduces transactivation by the ADA complex. 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). Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.
,This section provides any useful information about the protein, mostly biological knowledge.
. Information Product Use Citations Product Validations; S1322: Dexamethasone .Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).
Manual assertion inferred from combination of experimental and computational evidencei, Manual assertion inferred from combination of experimental and computational evidencei, jPOST - Japan Proteome Standard Repository/Database, MassIVE - Mass Spectrometry Interactive Virtual Environment, PaxDb, a database of protein abundance averages across all three domains of life, ProteomicsDB: a multi-organism proteome resource, GlyGen: Computational and Informatics Resources for Glycoscience, iPTMnet integrated resource for PTMs in systems biology context. 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 (PubMed:29127155). Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain (PubMed: Glucocorticoid receptor (Nuclear receptor subfamily 3, group C, member 1 (Glucocorticoid receptor)),An evidence describes the source of an annotation, e.g.
,When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later.
,This indicates the type of evidence that supports the existence of the protein. Encoded by exons 2-7 plus several basepairs from the subsequent intron region. The sequence of this isoform differs from the canonical sequence as follows: 1-89: Missing. Metab. The information is filed in different subsections. Acad. Epub 2019 Jun 1. in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. You are using a version of browser that may not display all the features of this website. with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018. U.S.A. 112:5479-5484(2015), J. Clin. Glucocorticoid, a kind of steroid hormone in the body, exerts diverse physiological functions via the glucocorticoid receptor (GR), which is expressed in almost all tissues (3, 4).
However UniProtKB may contain entries with identical sequences in case From: Principles of Medical Biology, 1997. Poor glucocorticoid receptor function due to chronic stress and high CRH can lead to cortisol resistance, possibly ⦠Corcept Therapeutics Incorporated, Menlo Park, ⦠GLUCOCORTICOID RECEPTOR FZW85LW99M Overview Names 4: Identifiers 2: Subunits 1: Other Links 2: Relationships 31: Modifications 4: Characteristic Attributes 1: Audit Info References 20: Substance Class: Protein Protein Sub Type: Sequence Type: ⦠Manual assertion based on experiment ini, Manual assertion inferred from sequence similarity toi,
Manual validated information which has been generated by the UniProtKB automatic annotation system.
Catalog No. GRβ is also expressed ubiquitously, does not bind glucocorticoids and has a dominant negative activity upon the GRα-induced transcriptional activity [8, 9]. Reduces transactivation activity; does not affect transrepression activity. The information is extracted from the scientific literature and diseases that are also described in the OMIM database are represented with a controlled vocabulary in the following way:,This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.
. Bethesda, MD 20894, Copyright Biophys. Metab. Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). 85:2519-2525(2000), Proc. C6 glioma and JScl1 Schwannoma cells were observed to express moderate to high levels of GR. Metab. Additionally, this section gives relevant information on each alternative protein isoform. Accounts for up to 10-20% of mRNAs. Glucocorticoid receptor (GR) isoforms and structure. Bgee dataBase for Gene Expression Evolution, ExpressionAtlas, Differential and Baseline Expression, Genevisible search portal to normalized and curated expression data from Genevestigator. in GCCR; interferes with translocation to the nucleus and thereby strongly reduces transcription activation; is equally impaired in nuclear export; acts as dominant negative mutant. No effect on transactivation by dexamethasone. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.,This subsection of the Names and taxonomy section is present for entries that are part of a proteome, i.e. 99:E902-E907(2014), Proc. Unable to load your collection due to an error, Unable to load your delegates due to an error. in isoform GR-A alpha and isoform GR-A beta.
Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.
Acad. The sequence of this isoform differs from the canonical sequence as follows: 1-330: Missing. Glucocorticoid receptors are a type of receptors on the outside of cells that transmit signals from glucocorticoids, such as cortisol. This entry has 16 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All. Endocrinol. It is Glucocorticoid Receptors of Type II. 89:4004-4009(2004), J. Clin.This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.
,This subsection of the 'Interaction' section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the 'Function' section).
,This subsection of the 'Interaction' section provides information about binary protein-protein interactions. Sci. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. 2019 Jul 15;411:255-269. doi: 10.1016/j.neuroscience.2019.05.050. In the brain, two types of high-affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II, glucocorticoid receptor (GR). 86:5600-5608(2001), J. Clin.
What is the canonical sequence?
canonicali sequence. 2017;2017:8640970. doi: 10.1155/2017/8640970. Responses to administration of exogenous glucocorticoids in individual patients can be highly variable; accordingly, therapeutic doses are often titrated upward or downward to achieve desired clinical effects (1â5). These results demonstrate that, in vitro, all classes of glial cells express glucocorticoid receptors that can translocate to the nucleus in the presence of hormone. in GCCR; reduces transactivation of the glucocorticoid-inducible tumor virus promoter; reduces affinity for ligand; delays its nuclear translocation; acts as dominant negative mutant. Aggregation and nuclear localization of expanded polyglutamine proteins are regulated cellular processes that can be modulated by this receptor, a well-characterized transcriptional regulator. Here, were aimed to examine whether glucocorticoid receptor directly influences RANKL promoter activity and its transcriptional regulation. Consequences of early adverse rearing experience(EARE) on development: insights from non-human primate studies. In the brain, two types of high-affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the ⦠1992;6(4):245-57. doi: 10.1002/glia.440060402. Strongly reduces transactivation by the ADA complex; when associated with A-194 and V-224. ,This subsection of the Function section specifies the position(s) and type(s) of zinc fingers within the protein.
,The Gene Ontology (GO) project provides a set of hierarchical controlled vocabulary split into 3 categories:
,Inferred from Direct Assay
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