'''Progesterone receptor membrane component 1''' (abbreviated '''PGRMC1''') is a [[protein]] which co-purifies with progesterone binding proteins in the liver and ovary.<ref name="pmid8774719">{{cite journal | author = Meyer C, Schmid R, Scriba PC, Wehling M | title = Purification and partial sequencing of high-affinity progesterone-binding site(s) from porcine liver membranes | journal = Eur. J. Biochem. | volume = 239 | issue = 3 | pages = 726–31 | year = 1996 | month = August | pmid = 8774719 | url = http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1996&volume=239&issue=3&spage=726 | issn = }}</ref><ref name="peluso2008b">{{cite journal | author = Peluso JJ, Romak J, Liu X | title = Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone's antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations | journal = Endocrinology | volume = 149 | issue = 2 | pages = 534–43 | year = 2008 | month = February | pmid = 17991724 | doi = 10.1210/en.2007-1050 | url = | issn = }}</ref> Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone's antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations.<ref name="peluso2008b"/>

The sole biochemical function of PGRMC1 is [[heme]]-binding.<ref name="crudden2006">{{cite journal | author = Crudden G, Chitti RE, Craven RJ | title = Hpr6 (heme-1 domain protein) regulates the susceptibility of cancer cells to chemotherapeutic drugs | journal = J. Pharmacol. Exp. Ther. | volume = 316 | issue = 1 | pages = 448–55 | year = 2006 | month = January | pmid = 16234411 | doi = 10.1124/jpet.105.094631 | url = | issn = }}</ref><ref name="ghosh2005">{{cite journal | author = Ghosh K, Thompson AM, Goldbeck RA, Shi X, Whitman S, Oh E, Zhiwu Z, Vulpe C, Holman TR | title = Spectroscopic and biochemical characterization of heme binding to yeast Dap1p and mouse PGRMC1p | journal = Biochemistry | volume = 44 | issue = 50 | pages = 16729–36 | year = 2005 | month = December | pmid = 16342963 | doi = 10.1021/bi0511585 | url = | issn = }}</ref> PGRMC1 shares key structural motifs with [[cytochrome b5|cytochrome b₅]].<ref name="pmid12537557">{{cite journal | author = Mifsud W, Bateman A | title = Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain | journal = Genome Biol. | volume = 3 | issue = 12 | pages = RESEARCH0068 | year = 2002 | pmid = 12537557 | pmc = 151170 | url = http://genomebiology.com/1465-6906/3/RESEARCH0068 | issn = }}</ref> PGRMC1 binds and activates P450 proteins,<ref name="hughes2007">{{cite journal | author = Hughes AL, Powell DW, Bard M, Eckstein J, Barbuch R, Link AJ, Espenshade PJ | title = Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes | journal = Cell Metab. | volume = 5 | issue = 2 | pages = 143–9 | year = 2007 | month = February | pmid = 17276356 | doi = 10.1016/j.cmet.2006.12.009 | url = | issn = }}</ref><ref name="pmid16279947">{{cite journal | author = Min L, Strushkevich NV, Harnastai IN, Iwamoto H, Gilep AA, Takemori H, Usanov SA, Nonaka Y, Hori H, Vinson GP, Okamoto M | title = Molecular identification of adrenal inner zone antigen as a heme-binding protein | journal = FEBS J. | volume = 272 | issue = 22 | pages = 5832–43 | year = 2005 | month = November | pmid = 16279947 | doi = 10.1111/j.1742-4658.2005.04977.x | url = | issn = }}</ref><ref name="min2004">{{cite journal | author = Min L, Takemori H, Nonaka Y, Katoh Y, Doi J, Horike N, Osamu H, Raza FS, Vinson GP, Okamoto M | title = Characterization of the adrenal-specific antigen IZA (inner zone antigen) and its role in the steroidogenesis | journal = Mol. Cell. Endocrinol. | volume = 215 | issue = 1-2 | pages = 143–8 | year = 2004 | month = February | pmid = 15026187 | doi = 10.1016/j.mce.2003.11.025 | url = | issn = }}</ref> which are important in drug, hormone and lipid metabolism. PGRMC1 also binds to PAIRBP1 [plasminogen activator inhibitor 1 [[mRNA]] binding protein.<ref name="peluso2008b" /> However, its expression outside of the reproductive tract and in males suggests multiple functions for the protein. These may include binding to Insig (insulin-induced gene),<ref name="pmid15782218">{{cite journal | author = Suchanek M, Radzikowska A, Thiele C | title = Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells | journal = Nat. Methods | volume = 2 | issue = 4 | pages = 261–7 | year = 2005 | month = April | pmid = 15782218 | doi = 10.1038/nmeth752 | url = | issn = }}</ref> which regulates cholesterol synthesis.<ref name="pmid12202038">{{cite journal | author =Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS | title = Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER | journal = Cell | volume = 110 | issue = 4 | pages = 489–500 | year = 2002 | month = August | pmid = 12202038 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/S0092867402008723 | issn = }}</ref>

PGRMC1 is highly expressed in the liver and kidney in humans<ref name="gerdes1998">{{cite journal | author = Gerdes D, Wehling M, Leube B, Falkenstein E | title = Cloning and tissue expression of two putative steroid membrane receptors | journal = Biol. Chem. | volume = 379 | issue = 7 | pages = 907–11 | year = 1998 | month = July | pmid = 9705155 | doi = | url = | issn = }}</ref> with lower expression in the brain, lung, heart, skeletal muscle and pancreas <ref name="gerdes1998" /><ref name="krebs2000">{{cite journal | author = Krebs CJ, Jarvis ED, Chan J, Lydon JP, Ogawa S, Pfaff DW | title = A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 23 | pages = 12816–21 | year = 2000 | month = November | pmid = 11070092 | pmc = 18847 | doi = 10.1073/pnas.97.23.12816 | url = | issn = }}</ref><ref name="selmin1996">{{cite journal | author = Selmin O, Lucier GW, Clark GC, Tritscher AM, Vanden Heuvel JP, Gastel JA, Walker NJ, Sutter TR, Bell DA | title = Isolation and characterization of a novel gene induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver | journal = Carcinogenesis | volume = 17 | issue = 12 | pages = 2609–15 | year = 1996 | month = December | pmid = 9006096 | url = http://carcin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9006096 | issn = }}</ref> In rodents, PGRMC1 is found in the liver, lung, kidney and brain.<ref name="krebs2000" /><ref name="selmin1996" /> PGRMC1 is over-expressed in breast tumors and in cancer cell lines from the colon, thyroid, ovary, lung, and cervix.<ref name="pmid15970648">{{cite journal | author = Crudden G, Loesel R, Craven RJ | title = Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors | journal = Tumour Biol. | volume = 26 | issue = 3 | pages = 142–6 | year = 2005 | pmid = 15970648 | doi = 10.1159/000086485 | url = | issn = }}</ref><ref name="pmid18319313">{{cite journal | author = Peluso JJ, Liu X, Saunders MM, Claffey KP, Phoenix K | title = Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1 | journal = J. Clin. Endocrinol. Metab. | volume = 93 | issue = 5 | pages = 1592–9 | year = 2008 | month = May | pmid = 18319313 | doi = 10.1210/jc.2007-2771 | url = | issn = }}</ref> [[Microarray]] analyses have detected PGRMC1 expression in colon, lung and breast tumors.<ref name="pmid12932674">{{cite journal | author = Difilippantonio S, Chen Y, Pietas A, Schlüns K, Pacyna-Gengelbach M, Deutschmann N, Padilla-Nash HM, Ried T, Petersen I | title = Gene expression profiles in human non-small and small-cell lung cancers | journal = Eur. J. Cancer | volume = 39 | issue = 13 | pages = 1936–47 | year = 2003 | month = September | pmid = 12932674 | url = http://linkinghub.elsevier.com/retrieve/pii/S0959804903004192 | issn = }}</ref><ref name="pmid16467094">{{cite journal | author = Dressman HK, Hans C, Bild A, Olson JA, Rosen E, Marcom PK, Liotcheva VB, Jones EL, Vujaskovic Z, Marks J, Dewhirst MW, West M, Nevins JR, Blackwell K | title = Gene expression profiles of multiple breast cancer phenotypes and response to neoadjuvant chemotherapy | journal = Clin. Cancer Res. | volume = 12 | issue = 3 Pt 1 | pages = 819–26 | year = 2006 | month = February | pmid = 16467094 | doi = 10.1158/1078-0432.CCR-05-1447 | url = | issn = }}</ref><ref name="pmid15753379">{{cite journal | author = Irby RB, Malek RL, Bloom G, Tsai J, Letwin N, Frank BC, Verratti K, Yeatman TJ, Lee NH | title = Iterative microarray and RNA interference-based interrogation of the SRC-induced invasive phenotype | journal = Cancer Res. | volume = 65 | issue = 5 | pages = 1814–21 | year = 2005 | month = March | pmid = 15753379 | doi = 10.1158/0008-5472.CAN-04-3609 | url = | issn = }}</ref>

PGRMC1 expression is induced by the non-genotoxic [[carcinogen]] 2,3,7,8-tetrachlorodibenzo-p-Dioxin in the rat liver,<ref name="selmin1996" /> but this induction is specific to males.<ref name="pmid15570619">{{cite journal | author = Selmin O, Thorne PA, Blachere FM, Johnson PD, Romagnolo DF | title = Transcriptional activation of the membrane-bound progesterone receptor (mPR) by dioxin, in endocrine-responsive tissues | journal = Mol. Reprod. Dev. | volume = 70 | issue = 2 | pages = 166–74 | year = 2005 | month = February | pmid = 15570619 | doi = 10.1002/mrd.20090 | url = | issn = }}</ref> PGRMC1 is expressed in the ovary and [[corpus luteum]], where its expression is induced by progesterone<ref name="pmid17127748">{{cite journal | author = Nilsson EE, Stanfield J, Skinner MK | title = Interactions between progesterone and tumor necrosis factor-alpha in the regulation of primordial follicle assembly | journal = Reproduction | volume = 132 | issue = 6 | pages = 877–86 | year = 2006 | month = December | pmid = 17127748 | doi = 10.1530/REP-06-0045 | url = | issn = }}</ref> and during pregnancy,<ref name="pmid16123161">{{cite journal | author = Cai Z, Stocco C | title = Expression and regulation of progestin membrane receptors in the rat corpus luteum | journal = Endocrinology | volume = 146 | issue = 12 | pages = 5522–32 | year = 2005 | month = December | pmid = 16123161 | doi = 10.1210/en.2005-0759 | url = | issn = }}</ref> respectively. PGRMC1/25-Dx is expressed in various regions of the brain [hypothalamic area, circumventricular organs, ependymal cells of the lateral ventricles, meninges.<ref name="krebs2000" /><ref name="pmid15934950">{{cite journal | author = Meffre D, Delespierre B, Gouézou M, Leclerc P, Vinson GP, Schumacher M, Stein DG, Guennoun R | title = The membrane-associated progesterone-binding protein 25-Dx is expressed in brain regions involved in water homeostasis and is up-regulated after traumatic brain injury | journal = J. Neurochem. | volume = 93 | issue = 5 | pages = 1314–26 | year = 2005 | month = June | pmid = 15934950 | doi = 10.1111/j.1471-4159.2005.03127.x | url = | issn = }}</ref> including regions known to facilitate [[lordosis]].<ref name="krebs2000" />

The PGRMC1 yeast homologue, Dap1 (damage associated protein 1), binds heme<ref name="ghosh2005" /><ref name="mallory2005">{{cite journal | author = Mallory JC, Crudden G, Johnson BL, Mo C, Pierson CA, Bard M, Craven RJ | title = Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae | journal = Mol. Cell. Biol. | volume = 25 | issue = 5 | pages = 1669–79 | year = 2005 | month = March | pmid = 15713626 | pmc = 549369 | doi = 10.1128/MCB.25.5.1669-1679.2005 | url = | issn = }}</ref> through a penta-coordinate mechanism.<ref name="ghosh2005" /><ref name="pmid18031064">{{cite journal | author = Thompson AM, Reddi AR, Shi X, Goldbeck RA, Moënne-Loccoz P, Gibney BR, Holman TR | title = Measurement of the heme affinity for yeast dap1p, and its importance in cellular function | journal = Biochemistry | volume = 46 | issue = 50 | pages = 14629–37 | year = 2007 | month = December | pmid = 18031064 | doi = 10.1021/bi7013739 | url = | issn = }}</ref> Yeast cells lacking the DAP1 gene are sensitive to DNA damage,<ref name="hand2003b">{{cite journal | author = Hand RA, Jia N, Bard M, Craven RJ | title = Saccharomyces cerevisiae Dap1p, a novel DNA damage response protein related to the mammalian membrane-associated progesterone receptor | journal = Eukaryotic Cell | volume = 2 | issue = 2 | pages = 306–17 | year = 2003 | month = April | pmid = 12684380 | pmc = 154842 | doi = | url = http://ec.asm.org/cgi/pmidlookup?view=long&pmid=12684380 | issn = }}</ref> and heme-binding is essential for damage resistance.<ref name="mallory2005" /> Dap1 is also required for a critical step in cholesterol synthesis in which the P450 protein Erg11/Cyp51 removes a methyl group from lanosterol.<ref name="craven2007">{{cite journal | author = Craven RJ, Mallory JC, Hand RA | title = Regulation of iron homeostasis mediated by the heme-binding protein Dap1 (damage resistance protein 1) via the P450 protein Erg11/Cyp51 | journal = J. Biol. Chem. | volume = 282 | issue = 50 | pages = 36543–51 | year = 2007 | month = December | pmid = 17954932 | doi = 10.1074/jbc.M706770200 | url = | issn = }}</ref><ref name="hand2003b" /><ref name="hughes2007"/><ref name="Mallory2005">{{cite journal | author = Mallory JC, Crudden G, Johnson BL, Mo C, Pierson CA, Bard M, Craven RJ | title = Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae | journal = Mol. Cell. Biol. | volume = 25 | issue = 5 | pages = 1669–79 | year = 2005 | month = March | pmid = 15713626 | pmc = 549369 | doi = 10.1128/MCB.25.5.1669-1679.2005 | url = | issn = }}</ref> Erg11/Cyp51 is the target of the azole antifungal drugs. As a result, yeast cells lacking the DAP1 gene are highly sensitive to antifungal drugs <ref name="hand2003b" /><ref name="hughes2007"/><ref name="Mallory2005"/> This function is conserved between the unrelated fungi [[Saccharomyces cerevisiae]] and [[Schizosaccharomyces pombe]]. Dap1 also regulates the metabolism of iron in yeast.<ref name="craven2007" />.

In yeast and humans, PGRMC1 binds directly to P450 proteins, including [[CYP51A1]], [[CYP3A4]], [[CYP7A1]] and [[CYP21A2]].<ref name="hughes2007"> PGRMC1 also activates Cyp21 when the two proteins are co-expressed,<ref name="pmid16279947">{{cite journal | author = Min L, Strushkevich NV, Harnastai IN, Iwamoto H, Gilep AA, Takemori H, Usanov SA, Nonaka Y, Hori H, Vinson GP, Okamoto M | title = Molecular identification of adrenal inner zone antigen as a heme-binding protein | journal = FEBS J. | volume = 272 | issue = 22 | pages = 5832–43 | year = 2005 | month = November | pmid = 16279947 | doi = 10.1111/j.1742-4658.2005.04977.x | url = | issn = }}</ref><ref name="min2004" /> indicating that PGRMC1 promotes progesterone turnover. Just as Dap1 is required for the action of Erg11 in the sythesis of ergosterol in yeast, PGRMC1 regulates the Cyp51-catalyzed demethylation step in human cholesterol synthesis.<ref name="hughes2007"> Thus, PGRMC1 and its homologues bind and regulate P450 proteins, and it has been likened to “a helping hand for P450 proteins”.<ref name="pmid17276348">{{cite journal | author = Debose-Boyd RA | title = A helping hand for cytochrome p450 enzymes | journal = Cell Metab. | volume = 5 | issue = 2 | pages = 81–3 | year = 2007 | month = February | pmid = 17276348 | doi = 10.1016/j.cmet.2007.01.007 | url = | issn = }}</ref>

The yeast PGRMC1 homologue is required for resistance to damage.<ref name="hand2003b" /> PGRMC1 also promotes survival in human cancer cells after treatment with chemotherapy.<ref name="crudden2006" /><ref name="peluso2008b" /> In contrast, PGRMC1 promotes cell death in cancer cells after oxidative damage.<ref name="hand2003a">{{cite journal | author = Hand RA, Craven RJ | title = Hpr6.6 protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells | journal = J. Cell. Biochem. | volume = 90 | issue = 3 | pages = 534–47 | year = 2003 | month = October | pmid = 14523988 | doi = 10.1002/jcb.10648 | url = | issn = }}</ref> PGRMC1 alters several known survival signaling proteins, including the [[Akt]] [[protein kinase]] and the cell death-associated protein [[IκB]].<ref name="hand2003a" /> Progesterone inhibits apoptosis in immortalized [[granulosa cells]], and this activity requires PGRMC1 and its binding partner, PAIRBP1 [plasminogen activator inhibitor 1 mRNA binding protein.<ref name="peluso2008b" /> However, PAIR-BP1 is not a progesterone binding protein, and the component of the PGRMC1 complex that binds to progesterone is unknown.