LMP012406 UniProt Annotations
Gene Name nuclear receptor subfamily 3, group C, member 1 Protein Entry GCR_RAT UniProt ID P06536 Species Rat
Comment type Description Alternative Products Event=Alternative initiation; Named isoforms=2; Name=A; IsoId=P06536-1; Sequence=Displayed; Name=B; IsoId=P06536-2; Sequence=VSP_018969; Domain Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. Function Receptor for glucocorticoids (GC). 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. 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. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression (By similarity) Interaction Q62667:Mvp; NbExp=2; IntAct=EBI-1187143, EBI-918333; Q15788:NCOA1 (xeno); NbExp=2; IntAct=EBI-1187143, EBI-455189; P51532:SMARCA4 (xeno); NbExp=3; IntAct=EBI-1187143, EBI-302489; Q96GM5:SMARCD1 (xeno); NbExp=2; IntAct=EBI-1187143, EBI-358489; Ptm Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity Ptm Increased proteasome-mediated degradation in response to glucocorticoids. Ptm Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoids. May be dephosphorylated by PPP5C, attenuates NR3C1 action (By similarity) Ptm Sumoylations at Lys-297 and Lys-313 negatively regulate its transcriptional activity. Sumoylation at Lys-721 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylations at Lys-297 and Lys-313 are dispensable whereas sumoylation at Lys-721 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWWD3-dependent manner Ptm Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling Similarity Belongs to the nuclear hormone receptor family. NR3 subfamily Similarity Contains 1 nuclear receptor DNA-binding domain Subcellular Location Cytoplasm . Mitochondrion {ECO:0000250}. Nucleus . Note=Cytoplasmic in the absence of ligand, nuclear after ligand- binding Subunit Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C. 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. Directly interacts with UNC45A. Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers. Interacts with NRIP1, POU2F1, POU2F2 and TRIM28. Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6. Interaction with BAG1 inhibits transactivation. Interacts with HEXIM1, PELP1 and TGFB1I1. Interacts with NCOA1, NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1. Interacts with CLOCK, CRY1 and CRY2 in a ligand- dependent fashion. Interacts with CIART. Interacts with RWDD3. Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3. {ECO:0000269|PubMed:10364267, ECO:0000269|PubMed:10480874, ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:12118039, ECO:0000269|PubMed:12917342, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:9111344}.
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