Membrane progesterone receptor (mPR) and Progesterone receptor membrane component (PGRMC) (mPR and PGRMC)

Membrane progesterone receptors (mPRs) and Progesterone receptor membrane components (PGRMC1 and PGRMC2) are two distinct families of proteins that mediate the rapid, non-genomic effects of progesterone. Unlike the classical nuclear progesterone receptor, these membrane-associated proteins trigger immediate intracellular signaling cascades, such as G protein activation and kinase pathways. mPRs belong to the progestin and adipoQ receptor (PAQR) family and are primarily involved in reproductive functions like oocyte maturation and sperm motility, as well as neuroprotection. PGRMC1 and PGRMC2 are members of the membrane-associated progesterone receptor (MAPR) family, characterized by a cytochrome b5-like heme-binding domain. PGRMC1 is frequently overexpressed in various cancers, including breast, ovarian, and lung, where it promotes cell survival, chemoresistance, and tumor progression by interacting with epidermal growth factor receptor (EGFR) and regulating cytochrome P450 enzymes. These proteins are emerging as significant therapeutic targets, with small molecules like AG-205 and CT1812 being explored for their ability to modulate their activity in oncology and neurodegenerative diseases.

Other names

PAQR7PAQR8PAQR5PAQR6PAQR9PGRMC1PGRMC225-DxDg6Progestin and adipoQ receptorMembrane-associated progesterone receptorMAPRSigma-2 receptor complex

mPRs (PAQR7-9) function as membrane receptors that activate G proteins (Gi, Gs, or Gq) to modulate intracellular cAMP and calcium levels, while PGRMC1 and PGRMC2 act as heme-binding adaptor proteins that regulate cytochrome P450 activity, stabilize the mitotic spindle, and activate survival pathways like PI3K/Akt.