Tclin NR3C1 Glucocorticoid receptor

Protein Summary

Description

Receptor for glucocorticoids (GC) (PubMed:27120390). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). 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 (PubMed:25775514). 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). Isoform Alpha: Has transcriptional activation and repression activity (PubMed:15866175, PubMed:19248771, PubMed:20484466, PubMed:23820903, PubMed:11435610, PubMed:15769988, PubMed:17635946, PubMed:19141540, PubMed:21664385). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity). Isoform Beta: Acts as a dominant negative inhibitor of isoform Alpha (PubMed:7769088, PubMed:8621628, PubMed:20484466). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253). Isoform Alpha-2: Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466). Isoform GR-P: Increases activity of isoform Alpha. Isoform Alpha-B: More effective than isoform Alpha in transcriptional activation, but not repression activity. Isoform 10: Has transcriptional activation activity. Isoform Alpha-C1: Has transcriptional activation activity. Isoform Alpha-C2: Has transcriptional activation activity. Isoform Alpha-C3: Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903). Isoform Alpha-D1: Has transcriptional activation activity. Isoform Alpha-D2: Has transcriptional activation activity. Isoform Alpha-D3: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175). [provided by RefSeq, Feb 2011]

Uniprot Accession IDs

• P04150
• A0ZXF9
• B0LPG8
• D3DQF4
• F5ATB7
• P04151
• Q53EP5
• Q6N0A4
• GR

Gene Name

• NR3C1

Ensembl ID

• ENST00000231509
• ENSP00000231509
• ENSG00000113580
• ENST00000343796
• ENSP00000343205
• ENST00000394464
• ENSP00000377977
• ENST00000394466
• ENSP00000377979
• ENST00000415690
• ENSP00000387672
• ENST00000424646
• ENSP00000405282
• ENST00000503201
• ENSP00000427672
• ENST00000504572
• ENSP00000422518

Symbol

• GRL
• GR
• GCR
• GRL
• GCCR
• GCRST

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
chemical	1
hub protein	1
molecular function	1
transcription factor perturbation	1

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Glucocorticoid Receptor

Protein / Receptor / Glucocorticoid Receptor

Protein / Nucleic Acid Binding / Glucocorticoid Receptor

Protein / ... / C4 Zinc Finger Nuclear Receptor / Glucocorticoid Receptor

DTO Classes

Protein / Nuclear Receptor / 3-ketosteroid Receptors / Glucocorticoid Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3248.35   (req: < 5)

Gene RIFs: 841   (req: <= 3)

Antibodies: 1148   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3248.35   (req: >= 5)

Gene RIFs: 841   (req: > 3)

Antibodies: 1148   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 31

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1750

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 71