Progesterone receptor membrane component 1 (PGRMC1) (PGRMC1)

Progesterone receptor membrane component 1 (PGRMC1) is a versatile, membrane-associated protein belonging to the membrane-associated progesterone receptor (MAPR) family, characterized by a cytochrome b5-like heme-binding domain (Kimura et al., 2012). Unlike classical nuclear steroid receptors, PGRMC1 mediates rapid, non-genomic signaling and acts as a scaffold for various signaling complexes, including those involving the epidermal growth factor receptor (EGFR) and cytochromes P450 (Cahill, 2007). It is highly expressed in various cancers, particularly breast and ovarian cancer, where it is often linked to estrogen receptor status and promotes tumor cell survival, chemoresistance, and proliferation (Neubauer et al., 2008). Beyond oncology, PGRMC1 plays significant roles in neuroprotection, cholesterol metabolism, and heme trafficking (Hasegawa et al., 2016). Its ability to bind progesterone and other steroids, coupled with its involvement in diverse cellular processes, makes it an emerging therapeutic target for cancer and neurodegenerative disorders like Alzheimer's disease. The protein's complex interactions with both estrogen and progesterone signaling pathways underscore its importance as a regulatory hub in steroid-sensitive tissues.

Other names

HPR6.6MAPRMembrane-associated progesterone receptor component 1Sigma-2 receptor (historical/disputed)Ventral node-associated proteinIZUMO1 receptor (IZA)

PGRMC1 acts as a non-genomic steroid receptor and a versatile scaffold protein that facilitates signaling through the EGFR and Src pathways. It also regulates the activity of cytochrome P450 enzymes and participates in heme-mediated dimerization to modulate cell survival and metabolic homeostasis (Cahill, 2007; Kimura et al., 2012).