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NR3C1

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]
Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Nuclear receptors, Plasma proteins, Transcription factors

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Excitatory neurons)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

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 (PubMed:29127155). Directly interacts with UNC45A (PubMed:16478993). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (By similarity). 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:12151000, PubMed:12686538, PubMed:9154805, PubMed:9590696). Interaction with BAG1 inhibits transactivation (PubMed:10477749). Interacts with HEXIM1 and TGFB1I1 (PubMed:12415108, PubMed:15211577, PubMed:15941832). Interacts with NCOA1 (PubMed:9590696). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (PubMed:19141540, PubMed:21980503, PubMed:22170608). Interacts with CIART (By similarity). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with GRIP1 (PubMed:15769988, PubMed:17635946). Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (PubMed:15591535). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (PubMed:25775514). Interacts with GSK3B (PubMed:18838540). Interacts with FNIP1 and FNIP2 (PubMed:27353360). Interacts (via C-terminus) with HNRNPU (via C-terminus) (PubMed:9353307). Interacts with MCM3AP (PubMed:16914116). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).

Molecular function

Chromatin regulator, DNA-binding, Receptor, RNA-binding

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