Domain:Composed of three domains: a modulating N-terminal domain , a DNA-binding domain and a C-terminal steroid-binding domain. ,Function:Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation. ,Function:The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation. ,online information:Progesterone receptor entry ,PTM:Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially on isoform B , is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81 , Ser-162 , Ser-190 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF , heregulin , IGF , PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent , and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-162 and Ser-294 , but not at Ser-190 , is impaired during the G (2) /M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1. ,PTM:Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388 , the main site of sumoylation , is repressed by ubiquitination on the same site , and modulated by phosphorylation at Ser-294. ,PTM:Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294. ,similarity:Belongs to the nuclear hormone receptor family. ,similarity:Belongs to the nuclear hormone receptor family. NR3 subfamily. ,similarity:Contains 1 nuclear receptor DNA-binding domain. ,subcellular location:Mainly nuclear. ,subcellular location:Nucleoplasmic shuttling is both homone- and cell cycle-dependent. On hormone stimulation , retained in the cytoplasm in the G (1) and G (2) /M phases. ,subunit:Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination , decreases sumoylation , and repesses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner , inhibits DNA-binding , and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-345 by ERK1/2 MAPK. ,
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