PGR

This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]

Progesterone Receptor

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor.
Isoform A
Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2.
Isoform B
Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation.
Isoform 4
Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.

Cell-cell signalingManual Assertion Based On ExperimentTAS:ProtInc
Epithelial cell maturationIEA:Ensembl
Intracellular steroid hormone receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Lung alveolus developmentIEA:Ensembl
Negative regulation of gene expressionManual Assertion Based On ExperimentIEP:UniProtKB
Ovulation from ovarian follicleIEA:Ensembl
Paracrine signalingIEA:Ensembl
Positive regulation of gene expression1 PublicationNAS:ARUK-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:NTNU_SB
Progesterone receptor signaling pathwayIEA:Ensembl
Regulation of epithelial cell proliferationIEA:Ensembl
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Tertiary branching involved in mammary gland duct morphogenesisIEA:Ensembl

Nucleus
Cytoplasm
Nucleoplasmic shuttling is both hormone- and cell cycle-dependent. On hormone stimulation, retained in the cytoplasm in the G1 and G2/M phases.
Isoform A
Nucleus
Cytoplasm
Mainly nuclear.
Isoform 4
Mitochondrion outer membrane

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 G2/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1.13 Publications
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.
Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294.
Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.