Membrane-associated progesterone receptor (MAPR) (MAPR)

Progesterone receptor membrane component 1 (PGRMC1) and 2 (PGRMC2) are the primary members of the membrane-associated progesterone receptor (MAPR) family, characterized by a conserved cytochrome b5-like heme-binding domain (Cahill, 2007, PMID: 17562114). Unlike classical nuclear progesterone receptors, these proteins are localized to the endoplasmic reticulum, mitochondria, and plasma membrane, where they mediate rapid, non-genomic effects of steroids (UniProt O00559). They play a vital role in regulating cytochrome P450 enzymes, cholesterol biosynthesis, and heme trafficking, which are essential for cellular homeostasis (Ruan et al., 2017, PMID: 29126691). In clinical contexts, PGRMC1 is significantly overexpressed in multiple cancer types, including breast, lung, and ovarian cancers, where it promotes tumor cell survival and chemoresistance by inhibiting apoptosis (Thejer et al., 2020, PMID: 32826445). Furthermore, PGRMC1 interacts with signaling complexes such as the Sigma-2 receptor (TMEM97) and EGFR to modulate cell growth and synaptic plasticity (Izzo et al., 2014, PMID: 25190611). Consequently, the MAPR family represents a promising therapeutic target for oncology and neurodegenerative diseases like Alzheimer's, with small molecule inhibitors like AG-205 being explored to disrupt these pro-survival pathways (Grundman et al., 2019, PMID: 31146695).

Other names

Progesterone receptor membrane component 1Progesterone receptor membrane component 2PGRMC1PGRMC2HPR6.625-DxVEMANeudesinNeuferricinSigma-2 receptor (historical)

Modulation of non-genomic steroid signaling and cytochrome P450 activity through heme-dependent protein-protein interactions and stabilization of membrane receptor complexes like EGFR and TMEM97 (PMID: 17562114, 29126691).