title: Functions of MAPR (membrane-associated progesterone receptor) family members as heme/steroid-binding proteins.
abstract: Progesterone receptor membrane component 1 (PGRMC1), PGRMC2, neudesin, and neuferricin all contain a cytochrome b5-like heme/steroid-binding domain and belong to the membrane-associated progesterone receptor (MAPR) family. Their amino acid sequences are well conserved among vertebrates, from humans to zebrafish. MAPR family genes are abundantly expressed in the central nervous system and exhibit neurotrophic effects in neural cells. During lipid metabolism, PGRMC1 regulates cholesterol synthesis, and neudesin plays a role in adipogenesis. Their bioactivities are dependent on the binding of heme to their cytochrome b5-like heme/steroid-binding domains. Conversely, it has been reported that the binding of steroids to MAPR family proteins induces biological responses that are unrelated to the nuclear steroid receptors. The interaction between PGRMC1 and progesterone promotes cell survival and damage resistance by progesterone. Moreover, MAPR family proteins exhibit a unique expression pattern in breast cancer, indicating the possibility of using MAPR family members as drug target in breast cancer. In this review, we summarize the identification, structure, and bioactivity of members of the MAPR family, and present an essential overview of the current understanding of their physiological roles.
authors.affiliation: Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo-ku, Kyoto 606-8501, Japan. ikimura@pharm.kyoto-u.ac.jp
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Morichika
authors.initials: M
authors.lastname: Konishi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Terasawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Itoh
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002490:Central Nervous System / Q000502:physiology; D002784:Cholesterol / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000502:physiology; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D006420:Hemeproteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C500818:NENF protein, human; D009419:Nerve Tissue Proteins; C115296:PGRMC1 protein, human; C115297:PGRMC2 protein, human; D011980:Receptors, Progesterone; C547758:neuferricin protein, mouse; D006418:Heme; D002784:Cholesterol