Affinage

PGRMC1

Membrane-associated progesterone receptor component 1 · UniProt O00264

Length
195 aa
Mass
21.7 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PGRMC1 is a heme-binding single-pass membrane protein that integrates steroid hormone signaling, heme metabolism, receptor trafficking, and ER quality control through its capacity to form heme-mediated homodimers and interact with diverse partners at multiple subcellular compartments. Its cytosolic domain coordinates heme via Tyr113, with face-to-face heme stacking driving dimerization that is required for interactions with EGFR (stabilizing plasma-membrane EGFR pools) and cytochromes P450, and is disrupted by carbon monoxide binding at the sixth coordination site (PMID:26988023); PGRMC1 also stabilizes CYP proteins post-transcriptionally in a heme-independent manner, interacts with ferrochelatase to regulate heme transfer, and serves as an adaptor trafficking mPRα to the cell surface (PMID:34678314, PMID:27599036, PMID:24424068). In the ER lumen, PGRMC1 functions as a size-selective cargo receptor that couples with RTN3 to deliver misfolded small prohormones to reticulophagy, and its lumenal domain activates PERK kinase independently of ER stress to phosphorylate eIF2α and suppress c-Myc translation (PMID:34645803, PMID:39747098). PGRMC1 additionally localizes to the mitotic spindle where it interacts with Aurora Kinase B to support completion of mitosis and meiosis, promotes store-operated Ca²⁺ entry through direct binding of STIM1, and participates with TMEM97 and LDLR in a ternary complex required for rapid LDL internalization (PMID:27260975, PMID:35045297, PMID:30443021).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2007 High

    Establishing that PGRMC1 directly binds progesterone and mediates its antiapoptotic action resolved the identity of the membrane component responsible for rapid, non-genomic progesterone signaling in granulosa cells.

    Evidence Radiolabeled progesterone binding on GFP-PGRMC1 fusion protein with siRNA depletion and domain deletion in granulosa cells

    PMID:17991724

    Open questions at the time
    • Binding was measured on tagged fusion protein; endogenous stoichiometry unknown
    • Whether progesterone directly binds PGRMC1 or requires heme occupancy was not resolved
  2. 2008 High

    Discovery that a patient-derived H165R mutation in the cytochrome b5 domain abolishes CYP7A1 binding and attenuates progesterone's antiapoptotic action linked PGRMC1 to premature ovarian failure and identified a critical residue for protein-protein interactions.

    Evidence Mutation screening in POF patient, co-immunoprecipitation with CYP7A1, progesterone antiapoptotic assay in ovarian cells

    PMID:18922159

    Open questions at the time
    • Only one patient studied; broader genetic contribution to POF not established
    • Structural basis for H165R disruption of binding unknown
  3. 2008 Medium

    Identification of Ser-56 and Ser-180 phosphorylation as modulators of oxidative stress-induced cell death revealed that PGRMC1's survival functions are regulated by post-translational modification rather than simple expression level.

    Evidence Site-directed mutagenesis (S56A/S180A) with peroxide cell-death assay in MCF7 cells

    PMID:18922159

    Open questions at the time
    • Kinases responsible for phosphorylation not identified
    • Single cell line tested
  4. 2010 High

    Demonstrating that PGRMC1 co-precipitates with EGFR and stabilizes its plasma membrane levels established a mechanistic link between PGRMC1 and growth factor receptor signaling in cancer cells.

    Evidence Reciprocal co-immunoprecipitation, confocal co-localization, subcellular fractionation, and pharmacological EGFR destabilization in tumor cell lines

    PMID:20538600

    Open questions at the time
    • Mechanism by which PGRMC1 stabilizes EGFR at the membrane was unknown
    • Whether heme binding was required was not addressed
  5. 2012 Medium

    Two parallel discoveries—progesterone-induced SUMO-1 modification suppressing Tcf/Lef transcription, and Pgrmc1-dependent ERK5-BDNF release in glia—expanded PGRMC1's roles to nuclear transcriptional regulation and neurotrophin signaling.

    Evidence Co-IP with SUMO-1, PLA, Tcf/Lef reporter with sumoylation-site mutagenesis; siRNA knockdown with BDNF ELISA and ERK5 inhibitors in glial cells

    PMID:22719051 PMID:22778217

    Open questions at the time
    • SUMO E3 ligase catalyzing PGRMC1 sumoylation not identified
    • Downstream targets of nuclear sumoylated PGRMC1 beyond Tcf/Lef unknown
    • ERK5 activation mechanism by PGRMC1 not resolved
  6. 2014 High

    Showing that PGRMC1 acts as an adaptor that traffics mPRα to the cell surface, and that the antiapoptotic effect of progestins depends on mPRα surface expression, reframed PGRMC1 as a trafficking facilitator rather than the sole progesterone effector.

    Evidence Stable transfection, co-immunoprecipitation, radioligand binding, mPRα siRNA abolishing progestin survival response

    PMID:24424068

    Open questions at the time
    • Trafficking route and vesicular intermediates not characterized
    • Whether PGRMC1's own progesterone binding is required for mPRα trafficking unclear
  7. 2014 Medium

    Localization of PGRMC1 to the mitotic spindle and demonstration that its depletion causes metaphase arrest and apoptosis established PGRMC1 as a cell-division factor beyond its steroid-signaling roles.

    Evidence siRNA knockdown, live imaging with FUCCI sensor, pull-down and PLA showing PGRMC1-PGRMC2-G3BP2 complex at spindle in granulosa cells

    PMID:25253729

    Open questions at the time
    • Molecular function of PGRMC1 at the spindle not defined
    • Whether heme binding is required for spindle localization unknown
  8. 2015 High

    Spectroscopic characterization of heme coordination by Tyr-95 (human numbering) with five-coordinate high-spin geometry, and demonstration that progesterone induces conformational changes around heme, provided the first biophysical framework for PGRMC1 as a heme-dependent sensor.

    Evidence UV-Vis and resonance Raman spectroscopy, site-directed mutagenesis (Y95C/F/H), redox potential measurement on purified recombinant protein

    PMID:25675345

    Open questions at the time
    • How progesterone-induced heme conformational change propagates to downstream signaling unknown
    • Physiological relevance of redox switching not tested in cells
  9. 2016 High

    The 1.95 Å crystal structure showing heme-stacking-driven dimerization and its disruption by CO provided the structural basis for PGRMC1's switch-like behavior: dimeric PGRMC1 binds EGFR and CYPs, while CO-induced monomerization disables these interactions.

    Evidence X-ray crystallography, Y113 mutagenesis, CO competition spectroscopy, co-IP with EGFR and CYPs, cancer proliferation and chemoresistance assays

    PMID:26988023

    Open questions at the time
    • Full-length structure including transmembrane and lumenal domains unavailable
    • In vivo CO concentrations needed to disrupt dimer not established
  10. 2016 High

    Identification of PGRMC1 as a ferrochelatase-binding partner that inhibits FECH activity and can transfer heme to apo-cytochrome b5 established a heme chaperone/regulatory function connecting PGRMC1 to heme biosynthesis.

    Evidence Reciprocal AP-MS, in vitro FECH activity assay, heme-transfer assay with purified proteins

    PMID:27599036

    Open questions at the time
    • Directionality of heme transfer in vivo not demonstrated
    • Whether PGRMC1 is a true chaperone or a regulatory inhibitor remains unclear
  11. 2016 Medium

    Demonstrating that PGRMC1 interacts with Aurora Kinase B at the central spindle/midbody and that its inhibition causes G2/M arrest and meiotic errors extended the mitotic role to a specific kinase partnership.

    Evidence Co-localization of PGRMC1 and AURKB, AG205 inhibitor and RNAi with cell-cycle analysis in bovine granulosa cells and oocytes

    PMID:27260975

    Open questions at the time
    • Whether PGRMC1 is an AURKB substrate or regulator not determined
    • Mechanism by which PGRMC1 supports cytokinesis unknown
  12. 2018 High

    Formation of a PGRMC1–TMEM97–LDLR ternary complex required for rapid LDL internalization linked PGRMC1 to cholesterol uptake and resolved the functional relationship between PGRMC1 and the sigma-2 receptor candidate TMEM97.

    Evidence CRISPR KO of PGRMC1 and TMEM97 (single and double), fluorescent LDL uptake, PLA in HeLa cells

    PMID:30443021

    Open questions at the time
    • Stoichiometry and direct contacts within the ternary complex not structurally resolved
    • Whether PGRMC1 regulates LDLR recycling or only surface delivery not addressed
  13. 2019 Medium

    Establishing that PGRMC1's C-terminus (residues 171–195) is extracellularly exposed overturned the predicted single-pass topology and has implications for all models of PGRMC1 ligand binding and partner interactions.

    Evidence Flow cytometry with epitope-mapped monoclonal antibodies, trypsin-protection assay on intact cells

    PMID:30679694

    Open questions at the time
    • How extracellular C-terminus reconciles with cytosolic heme coordination is not explained
    • Dual topology or multiple membrane-spanning conformations not ruled out
  14. 2021 High

    Discovery that PGRMC1 stabilizes >13 CYP proteins post-transcriptionally in a heme-independent manner (Y113F retains CYP binding) while requiring Y113-dependent heme coordination specifically for FECH binding dissected the dimer-dependent versus dimer-independent functions in vivo.

    Evidence Pgrmc1 knockout mouse liver proteomics and transcriptomics, Y113F mutagenesis, co-IP, acetaminophen toxicity model

    PMID:34678314

    Open questions at the time
    • Mechanism of heme-independent CYP stabilization not identified
    • Whether CYP stabilization involves ER retention or anti-degradation unknown
  15. 2021 High

    Identification of PGRMC1 as an ER-lumenal size-selective cargo receptor coupling with RTN3 for reticulophagy of misfolded prohormones revealed a fundamentally new function in ER quality control distinct from ERAD.

    Evidence Unbiased RTN3 interactome proteomics, reciprocal co-IP, domain deletions, CRISPR KO, live-cell imaging of mutant proinsulin turnover in β-cells

    PMID:34645803 PMID:34779709

    Open questions at the time
    • Size-selectivity determinants on the PGRMC1 lumenal domain not structurally mapped
    • Whether other ER-phagy receptors compensate in PGRMC1 absence not tested
  16. 2022 Medium

    Demonstrating that PGRMC1 directly binds the STIM1 coiled-coil domain to promote its conformational switch and store-operated Ca²⁺ entry connected PGRMC1 to calcium homeostasis and downstream NFAT activation.

    Evidence Complementation-dependent in situ labeling, co-IP, CRISPR depletion, Ca²⁺ imaging, NFAT reporter in breast cancer cells

    PMID:35045297

    Open questions at the time
    • Whether heme or dimerization status of PGRMC1 influences STIM1 interaction not tested
    • Relevance beyond breast cancer cells not established
  17. 2025 Medium

    Showing that the PGRMC1 lumenal domain directly activates PERK kinase independently of ER stress to phosphorylate eIF2α and suppress c-Myc translation established a tumor-suppressive signaling axis in hepatocarcinogenesis.

    Evidence Co-IP with domain deletions, PERK kinase activity assay, polysome profiling, orthotopic HCC mouse model

    PMID:39747098

    Open questions at the time
    • Whether PGRMC1–PERK activation occurs constitutively or is regulated by a specific signal unknown
    • Relationship between PGRMC1's ER-phagy receptor function and PERK activation not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural model reconciling PGRMC1's non-canonical membrane topology with its dual cytosolic heme-dimer and lumenal cargo-receptor/PERK-activating functions is still lacking, and how its diverse interactions are spatiotemporally partitioned across ER, plasma membrane, and mitotic spindle remains unresolved.
  • Full-length structure including transmembrane domain unavailable
  • How PGRMC1 distributes among its multiple compartments and switches between functions is mechanistically uncharacterized
  • Physiological ligand hierarchy (progesterone, heme, CO, partners) governing functional mode selection not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0038024 cargo receptor activity 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2 GO:0005739 mitochondrion 1 GO:0005811 lipid droplet 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 2 R-HSA-382551 Transport of small molecules 1 R-HSA-5357801 Programmed Cell Death 1
Partners
AURKBEGFRFECHPAQR7PGRMC2RTN3STIM1TMEM97
Complex memberships
PGRMC1-PGRMC2-G3BP2 spindle complexPGRMC1-TMEM97-LDLR ternary complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Crystal structure of the PGRMC1 cytosolic domain at 1.95 Å resolution reveals that heme iron is five-coordinated by Tyr113, and that two heme molecules from adjacent monomers stack face-to-face to drive stable homodimerization. CO binds the sixth coordination site of heme and disrupts dimerization. Heme-mediated dimerization is required for interactions with EGFR and cytochromes P450, and for cancer proliferation and chemoresistance. X-ray crystallography (1.95 Å), site-directed mutagenesis, CO competition assays, co-immunoprecipitation with EGFR and CYPs, cancer cell proliferation and drug-resistance assays Nature communications High 26988023
2011 A photoaffinity probe (WC-21) irreversibly labeled a membrane-bound protein in rat liver identified as PGRMC1, which co-localizes with ER and mitochondrial markers; overexpression increases and knockdown decreases binding of a sigma-2 selective radioligand, identifying PGRMC1 as the putative sigma-2 receptor-binding site. Photoaffinity labeling, fluorescent probe co-localization, radioligand binding with overexpression and siRNA knockdown Nature communications Medium 21730960
2010 PGRMC1 co-precipitates with EGFR, increases plasma membrane EGFR levels, co-localizes with EGFR in cytoplasmic vesicles and co-fractionates with EGFR in high-density microsomes; a PGRMC1 small-molecule ligand destabilizes EGFR in multiple tumor cell lines. Co-immunoprecipitation, confocal co-localization, subcellular fractionation, pharmacological perturbation The Journal of biological chemistry High 20538600
2021 PGRMC1 functions as a size-selective ER-lumenal cargo receptor for RTN3-dependent ER-phagy: via its lumenal domain PGRMC1 binds RTN3 on the cytosolic face and captures small misfolded prohormones (including mutant proinsulin and mutant POMC) on the lumenal face, targeting them for lysosomal degradation; genetic or pharmacological inactivation of PGRMC1 in β-cells impairs mutant proinsulin turnover and partially restores WT proinsulin trafficking. Unbiased proteomics/RTN3 interactome, co-immunoprecipitation, domain-deletion constructs, CRISPR knockout, live-cell imaging, pharmacological inhibition Nature communications High 34645803 34779709
2016 PGRMC1 interacts with ferrochelatase (FECH), the terminal heme biosynthetic enzyme; the interaction is strongest for the FECH conformation associated with product release, PGRMC1 inhibits FECH activity in vitro in a dose-dependent manner, and purified PGRMC1 can donate heme to apo-cytochrome b5, suggesting a heme chaperone or regulatory role. Affinity purification–mass spectrometry (reciprocal), in vitro pull-down, immunoblotting, in vitro FECH activity assay, in vitro heme-transfer assay, small-molecule inhibitor (AG-205) Biochemistry High 27599036
2021 Pgrmc1 knockout mouse liver shows reduced abundance of >13 cytochrome P450 proteins post-transcriptionally; PGRMC1 stabilizes CYPs through direct binding in a heme-independent manner (Y113F mutant lacking axial heme-iron coordination retains CYP binding). Proper iron coordination at Y113 is specifically required for binding to ferrochelatase. Pgrmc1 KO protects mice from acetaminophen-induced liver injury consistent with reduced CYP activity. Mouse knockout model, quantitative proteomics, transcriptomics, in vitro CYP activity assays, site-directed mutagenesis (Y113F), co-immunoprecipitation The Journal of biological chemistry High 34678314
2015 Human PGRMC1 binds heme in a five-coordinate high-spin configuration with an axial tyrosinate ligand at Y95; Y95C or Y95F mutations dramatically reduce heme binding while Y95H retains ~90% binding. Progesterone binding to heme-loaded hPGRMC1 induces conformational changes around the heme, providing direct evidence of progesterone binding to the purified protein. UV-Vis and resonance Raman spectroscopy, site-directed mutagenesis, redox potential measurement, progesterone-binding spectral assay Biochemistry High 25675345
2008 A missense mutation H165R in the cytochrome b5 domain of PGRMC1 (identified in a POF patient) abolishes binding of CYP7A1 to PGRMC1 and attenuates PGRMC1-mediated antiapoptotic action of progesterone in ovarian cells. Mutation screening, co-immunoprecipitation (CYP7A1 binding), cell-based progesterone antiapoptotic assay Human molecular genetics High 18782852
2007 PGRMC1 directly binds progesterone at a single site (Kd ~35 nM); siRNA depletion reduces [3H]P4 binding by 60% and abolishes progesterone's antiapoptotic action in granulosa cells. Deletion mutations show the transmembrane domain and initial C-terminus are required for P4 binding; PAIRBP1 binds PGRMC1 C-terminus (aa 70–130), distal to the P4 binding site. siRNA knockdown, [3H]progesterone binding assay on GFP-PGRMC1 fusion protein, deletion mutagenesis, cell survival assay Endocrinology High 17991724
2014 PGRMC1 acts as an adaptor protein that transports membrane progesterone receptor α (mPRα) to the cell surface; PGRMC1 overexpression increases mPRα membrane expression and specific [3H]progesterone binding, and co-immunoprecipitation/immunocytochemistry shows close association. The antiapoptotic effect of progestins previously attributed to PGRMC1 is abolished by mPRα siRNA, indicating dependence on mPRα surface expression. PGRMC1 similarly increases membrane expression of estrogen receptor β. Stable transfection, [3H]progesterone binding assay, G-protein activation assay, co-immunoprecipitation, immunocytochemistry, siRNA knockdown of mPRα Endocrinology High 24424068
2018 PGRMC1, TMEM97, and LDLR form a ternary complex required for rapid LDL internalization; CRISPR knockout of either PGRMC1 or TMEM97 alone equally reduces LDL uptake rate, and double knockout does not further reduce it. Co-localization confirmed by confocal microscopy and Proximity Ligation Assay. CRISPR/Cas9 gene editing, radioligand binding, fluorescence-tagged LDL internalization assay, confocal microscopy, Proximity Ligation Assay Scientific reports High 30443021
2012 Pgrmc1 knockdown in C6 glial cells and primary astrocytes abolishes progesterone-induced BDNF release; P4-induced BDNF release is mediated by ERK5 (not ERK1/2), establishing a Pgrmc1→ERK5→BDNF release signaling axis in glia. siRNA knockdown of Pgrmc1, BDNF ELISA, pharmacological ERK1/2 and ERK5 inhibitors, membrane-impermeable P4-BSA Endocrinology Medium 22778217
2012 Progesterone promotes PGRMC1 sumoylation (interaction with SUMO-1 confirmed by co-IP and in situ PLA); sumoylated PGRMC1 localizes to the nucleus and suppresses Tcf/Lef transcriptional activity in a PGRMC1-dependent manner. Mutation of all sumoylation sites abolishes progesterone's ability to suppress Tcf/Lef activity. Co-immunoprecipitation with SUMO-1, in situ Proximity Ligation Assay, Tcf/Lef luciferase reporter assay, sumoylation-site mutagenesis, siRNA knockdown Endocrinology Medium 22719051
2014 PGRMC1 and PGRMC2 localize to the mitotic spindle; depletion of either PGRMC1 or PGRMC2 in spontaneously immortalized granulosa cells increases G1-phase entry and causes metaphase arrest and apoptosis. Pull-down assays, co-localization and PLA show PGRMC1 binds PGRMC2 and both bind G3BP2; disrupting the PGRMC1:PGRMC2 complex increases cell-cycle entry. siRNA knockdown, live imaging, pull-down assay, co-localization, in situ Proximity Ligation Assay, FUCCI cell-cycle sensor Biology of reproduction Medium 25253729
2016 PGRMC1 localizes to the central spindle/mid-body in mitosis and interacts directly with Aurora Kinase B (AURKB) there; PGRMC1 inhibition or silencing in bovine granulosa cells causes G2/M arrest and defects in late karyokinesis, and in oocytes impairs first polar body extrusion and increases meiotic errors. Time-lapse imaging, RNA interference, PGRMC1 inhibitor (AG205), co-localization of PGRMC1 and AURKB, cell-cycle analysis Cell cycle (Georgetown, Tex.) Medium 27260975
2013 Microglial Pgrmc1 mediates progesterone antagonism of estrogen-induced neurite outgrowth: siRNA knockdown of Pgrmc1 in microglia before add-back to neuron-astrocyte cocultures suppresses P4-E2 antagonism of neurite sprouting, and conditioned media from Pgrmc1-knockdown microglia lose this activity, linking Pgrmc1 to microglial activation. siRNA knockdown, microglia add-back assay, neurite outgrowth quantification, conditioned media transfer Endocrinology Medium 23653459
2008 Phosphorylation of PGRMC1 at Ser-56 and Ser-180 modulates cell survival: simultaneous mutation of both sites fully abrogates sensitivity of MCF7 cells to peroxide-induced cell death, and differential PGRMC1 phosphorylation correlates with ER status in breast tumors. 2D-PAGE phosphatase treatment, site-directed mutagenesis (S56A/S180A), stable transfection, oxidative stress cell-death assay Breast cancer research : BCR Medium 18922159
2010 PGRMC1 localizes to the plasma membrane, cytoplasm, and nuclear membranes in human myometrial cells; pretreatment of myometrial strips with a PGRMC1 antibody suppresses progesterone-induced rapid relaxation of contractions, implicating PGRMC1 in non-genomic P4 action on uterine smooth muscle. Immunofluorescence subcellular localization, isometric contraction assay with blocking antibody Molecular human reproduction Medium 21131300
2022 PGRMC1 promotes store-operated Ca2+ entry (SOCE) by directly binding the coiled-coil domain of STIM1, promoting STIM1 conformational switch; PGRMC1 depletion reduces SOCE, impairs NFAT pathway activation, and disrupts EGF-induced focal adhesion turnover and actomyosin formation in breast cancer cells. Complementation-dependent in situ labeling (STIM1-Orai1 interactome), co-immunoprecipitation, CRISPR depletion, Ca2+ imaging, NFAT reporter, focal adhesion and actin staining Cell reports Medium 35045297
2021 PGRMC1 promotes progestin-dependent ERα transcriptional activity in breast cancer cells by interacting with prohibitins PHB1 and PHB2 in a manner dependent on phosphorylation of PGRMC1 at S181; increased PGRMC1-PHB binding correlates with decreased PHB-ERα binding, releasing ERα for transcriptional activation. Co-immunoprecipitation with mass spectrometry, phosphorylation-site mutant (S181A), ERα transcriptional assay, proliferation assay, pharmacological inhibition Cancers Medium 34830790
2020 Manipulation of PGRMC1 phosphorylation status (S57A/S181A double mutant or S57A/Y180F/S181A triple mutant) broadly alters energy metabolism, PI3K/AKT activity, cell shape, actin cytoskeleton, mitochondrial morphology, and xenograft tumor growth; Y180F mutation strongly attenuates tumor growth in vivo. Stable transfection of phospho-mutants, proteomics, metabolic assays, PI3K/AKT phospho-blotting, live-cell imaging, xenograft tumor model BMC molecular and cell biology Medium 32245408
2015 Pgrmc1 is required for EGFR expression on zebrafish oocyte cell membranes and for EGFR-dependent estrogen (GPER1) signaling that maintains meiotic arrest; PGRMC1 inhibitor AG205 blocks estradiol/GPER agonist inhibition of oocyte maturation and decreases membrane EGFR levels. Pharmacological inhibition (AG205, AG1478, AG825), western blot of membrane fractions, oocyte maturation bioassay The Journal of endocrinology Medium 25720537
2018 Global pgrmc1 knockout in zebrafish reduces sensitivity of oocytes to progestin-induced maturation in vivo and in vitro, and significantly reduces mPRα (Paqr7) expression, indicating that Pgrmc1 regulates oocyte maturation at least in part by maintaining mPRα expression. CRISPR/Cas9 knockout zebrafish, spawning frequency assay, in vitro oocyte maturation assay, western blot and qPCR for mPRα Frontiers in endocrinology Medium 30319543
2019 PGRMC1 knockout (CRISPR) reduces binding affinity (but not site density) of sigma-2 radioligands, whereas TMEM97 KO causes complete loss of [125I]RHM-4 binding, demonstrating that PGRMC1 modulates but is not the primary sigma-2 receptor, and that PGRMC1, TMEM97, and LDLR co-localize by PLA. CRISPR/Cas9 knockout, radioligand binding (Scatchard), confocal microscopy, Proximity Ligation Assay Cell death discovery Medium 30701090
2025 PGRMC1 localizes to the ER membrane where its lumenal domain directly interacts with the PERK kinase lumenal domain; this interaction activates PERK in an ER stress-independent manner, leading to eIF2α phosphorylation and consequent inhibition of c-Myc protein translation, thereby blocking c-Myc-induced hepatocarcinogenesis. Co-immunoprecipitation, domain-deletion constructs, orthotopic HCC mouse model, PERK kinase activity assay, polysome/translation assay, CRISPR Nature communications Medium 39747098
2016 CO acts as a sensor that binds the sixth coordination site of heme in PGRMC1, dissociating the heme-stacking dimer and thereby attenuating PGRMC1's interactions with EGFR and cytochromes P450. CO competition assay (spectroscopy), dimerization assay, EGFR co-immunoprecipitation (referenced from crystallography paper 26988023) Free radical biology & medicine Medium 26988023 27565814
2018 In ER-phagy context, PGRMC1 co-localizes with LC3B-II and promotes autophagic clearance; PGRMC1 interaction with LC3B2 is inhibited by UTMD treatment, and PGRMC1 overexpression blocks autophagosome-lysosome fusion arrest caused by UTMD, confirming a direct role of PGRMC1 in autophagic flux regulation in glioblastoma. Co-immunoprecipitation (PGRMC1-LC3B2), western blot, confocal autophagy assays, siRNA and overexpression, in vivo glioblastoma mouse model Military Medical Research Low 35152910
2024 In trophoblast cells (JEG3) lacking classical PRs but expressing PGRMC1, progesterone upregulates HLA-C, HLA-G, and transcription factor ELF3; CRISPR knockout of PGRMC1 abolishes these progesterone responses, and RU486 inhibits ELF3 expression and cell invasion in a PGRMC1-dependent manner. CRISPR/Cas9 knockout, RT-qPCR and western blot, single-cell RNA-seq mining, cell invasion assay Journal of reproductive immunology Medium 38555747
2021 PGRMC1 promotes ferroptosis sensitivity in paclitaxel-tolerant persister cancer cells by increasing fatty acid oxidation and lipophagy; PGRMC1 silencing reduces ferroptosis induced by xCT inhibitors and PGRMC1 overexpression increases it, with PGRMC1 colocalizing with lipid droplets and LC3B-II during lipophagy. siRNA silencing, overexpression, lipid ROS measurement, lipid droplet quantification, autophagosome imaging, mouse xenograft model Journal of experimental & clinical cancer research Medium 34749765
2019 PGRMC1 has a non-conventional plasma membrane topology in which the C-terminus (residues 171–195) is exposed on the extracellular face, opposite to the predicted topology; this was established by epitope mapping with anti-PGRMC1 monoclonal antibodies and trypsin-sensitivity assays on intact cells. Flow cytometry, trypsin-protection assay, GST-PGRMC1 mutant epitope mapping, antibody binding competition Scientific reports Medium 30679694

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site. Nature communications 271 21730960
2008 PGRMC1 (progesterone receptor membrane component 1): a targetable protein with multiple functions in steroid signaling, P450 activation and drug binding. Pharmacology & therapeutics 170 18992768
2014 Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity. PloS one 168 25390692
2007 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. Endocrinology 156 17991724
2016 Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance. Nature communications 153 26988023
2010 Progesterone receptor membrane component 1 (Pgrmc1): a heme-1 domain protein that promotes tumorigenesis and is inhibited by a small molecule. The Journal of pharmacology and experimental therapeutics 119 20164297
2014 Enhancement of cell surface expression and receptor functions of membrane progestin receptor α (mPRα) by progesterone receptor membrane component 1 (PGRMC1): evidence for a role of PGRMC1 as an adaptor protein for steroid receptors. Endocrinology 115 24424068
2010 Pgrmc1 (progesterone receptor membrane component 1) associates with epidermal growth factor receptor and regulates erlotinib sensitivity. The Journal of biological chemistry 114 20538600
2018 Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Internalization of LDL by LDL Receptor through the Formation of a Ternary Complex. Scientific reports 112 30443021
2008 Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1. Breast cancer research : BCR 99 18922159
2008 Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure. Human molecular genetics 96 18782852
2016 A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase. Biochemistry 93 27599036
2021 PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells. Journal of experimental & clinical cancer research : CR 92 34749765
2016 The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Biochimica et biophysica acta 87 27452206
2017 ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells by NPRA/PGRMC1/EGFR complex and improves ovary functions of PCOS rats. Cell death & disease 80 29072679
2012 Progesterone increases the release of brain-derived neurotrophic factor from glia via progesterone receptor membrane component 1 (Pgrmc1)-dependent ERK5 signaling. Endocrinology 80 22778217
2020 The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates. Molecular neurobiology 67 32572762
2012 Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3. The Journal of clinical endocrinology and metabolism 64 22492871
2012 S2R(Pgrmc1): the cytochrome-related sigma-2 receptor that regulates lipid and drug metabolism and hormone signaling. Expert opinion on drug metabolism & toxicology 62 22292588
2003 Hpr6.6 protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells. Journal of cellular biochemistry 61 14523988
2015 Elements in support of the 'non-identity' of the PGRMC1 protein with the σ2 receptor. European journal of pharmacology 56 25843410
2014 Progesterone receptor membrane component-1 (PGRMC1) and PGRMC-2 interact to suppress entry into the cell cycle in spontaneously immortalized rat granulosa cells. Biology of reproduction 55 25253729
2015 Spectroscopic and mutagenesis studies of human PGRMC1. Biochemistry 54 25675345
2017 PGRMC1-dependent autophagy by hyperoside induces apoptosis and sensitizes ovarian cancer cells to cisplatin treatment. International journal of oncology 51 28197632
2013 PGRMC1 and PGRMC2 in uterine physiology and disease. Frontiers in neuroscience 49 24065879
2017 Thoughts on interactions between PGRMC1 and diverse attested and potential hydrophobic ligands. The Journal of steroid biochemistry and molecular biology 48 28104494
2015 Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr. The Journal of endocrinology 46 25720537
2010 Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS). Reproductive biology and endocrinology : RB&E 46 20537145
2019 TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death. Cell death discovery 44 30701090
2011 Differential responses of progesterone receptor membrane component-1 (Pgrmc1) and the classical progesterone receptor (Pgr) to 17β-estradiol and progesterone in hippocampal subregions that support synaptic remodeling and neurogenesis. Endocrinology 43 22147012
2010 Changes in PGRMC1, a potential progesterone receptor, in human myometrium during pregnancy and labour at term and preterm. Molecular human reproduction 43 21131300
2021 PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones. Nature communications 42 34645803
2015 Progestin and AdipoQ Receptor 7, Progesterone Membrane Receptor Component 1 (PGRMC1), and PGRMC2 and Their Role in Regulating Progesterone's Ability to Suppress Human Granulosa/Luteal Cells from Entering into the Cell Cycle. Biology of reproduction 42 26203174
2022 Ultrasound-triggered microbubble destruction enhances the radiosensitivity of glioblastoma by inhibiting PGRMC1-mediated autophagy in vitro and in vivo. Military Medical Research 41 35152910
2013 Possible role of PGRMC1 in breast cancer development. Climacteric : the journal of the International Menopause Society 41 23758160
2012 Progesterone regulation of progesterone receptor membrane component 1 (PGRMC1) sumoylation and transcriptional activity in spontaneously immortalized granulosa cells. Endocrinology 41 22719051
2013 Progesterone antagonism of neurite outgrowth depends on microglial activation via Pgrmc1/S2R. Endocrinology 39 23653459
2018 Pgrmc1 Knockout Impairs Oocyte Maturation in Zebrafish. Frontiers in endocrinology 38 30319543
2016 Sigma-2 receptor and progesterone receptor membrane component 1 (PGRMC1) are two different proteins: Proofs by fluorescent labeling and binding of sigma-2 receptor ligands to PGRMC1. Pharmacological research 37 28007569
2014 Progesterone receptor membrane component 1 (PGRMC1) expression in fetal membranes among women with preterm premature rupture of the membranes (PPROM). Placenta 37 24680695
2021 Progesterone receptor membrane component 1 (PGRMC1) binds and stabilizes cytochromes P450 through a heme-independent mechanism. The Journal of biological chemistry 34 34678314
2016 PGRMC1 regulation by phosphorylation: potential new insights in controlling biological activity. Oncotarget 34 27448967
2020 PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth. BMC molecular and cell biology 33 32245408
2015 PGRMC1 contributes to doxorubicin-induced chemoresistance in MES-SA uterine sarcoma. Cellular and molecular life sciences : CMLS 32 25596698
2016 PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival. Advances in lung cancer (Irvine) 30 27867772
2016 PGRMC1 participates in late events of bovine granulosa cells mitosis and oocyte meiosis. Cell cycle (Georgetown, Tex.) 29 27260975
2008 PGRMC1: a new biomarker for the estrogen receptor in breast cancer. Breast cancer research : BCR 29 19090968
2016 Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Cross Talk. Endocrinology 27 26990062
2019 Downregulation of nuclear progestin receptor (Pgr) and subfertility in double knockouts of progestin receptor membrane component 1 (pgrmc1) and pgrmc2 in zebrafish. General and comparative endocrinology 26 31536721
2017 The evolutionary appearance of signaling motifs in PGRMC1. Bioscience trends 26 28250339
2021 Progesterone Receptor Membrane Component (PGRMC)1 and PGRMC2 and Their Roles in Ovarian and Endometrial Cancer. Cancers 25 34885064
2010 Transcriptional analysis of novel hormone receptors PGRMC1 and PGRMC2 as potential biomarkers of breast adenocarcinoma staging. The Journal of surgical research 24 20655063
2021 PGRMC Proteins Are Coming of Age: A Special Issue on the Role of PGRMC1 and PGRMC2 in Metabolism and Cancer Biology. Cancers 23 33572771
2018 PGRMC1/2 promotes luteal vascularization and maintains the primordial follicles of mice. Reproduction (Cambridge, England) 23 30306772
2017 Dynamic expression of PGRMC1 and SERBP1 in human endometrium: an implication in the human decidualization process. Fertility and sterility 23 28911927
2013 Pgrmc1: new roles in the microglial mediation of progesterone-antagonism of estradiol-dependent neurite sprouting and in microglial activation. Frontiers in neuroscience 23 24027494
2022 PGRMC1: An enigmatic heme-binding protein. Pharmacology & therapeutics 22 36463977
2020 Identification of PGRMC1 as a Candidate Oncogene for Head and Neck Cancers and Its Involvement in Metabolic Activities. Frontiers in bioengineering and biotechnology 22 31970154
2020 Protein complexes including PGRMC1 and actin-associated proteins are disrupted by AG-205. Biochemical and biophysical research communications 22 31980178
2016 Norbenzomorphan Framework as a Novel Scaffold for Generating Sigma 2 Receptor/PGRMC1 Subtype-Selective Ligands. ChemMedChem 22 26915462
2021 PGRMC1 Promotes Progestin-Dependent Proliferation of Breast Cancer Cells by Binding Prohibitins Resulting in Activation of ERα Signaling. Cancers 21 34830790
2018 Progesterone maintains the status of granulosa cells and slows follicle development partly through PGRMC1. Journal of cellular physiology 21 30069867
2017 PGRMC1 Is a Novel Potential Tumor Biomarker of Human Renal Cell Carcinoma Based on Quantitative Proteomic and Integrative Biological Assessments. PloS one 21 28107520
2016 The PGRMC1 Protein Level Correlates with the Binding Activity of a Sigma-2 Fluorescent Probe (SW120) in Rat Brain Cells. Molecular imaging and biology 21 26335282
2016 Cystathionine β-synthase and PGRMC1 as CO sensors. Free radical biology & medicine 21 27565814
2013 Lipid synthesis and processing proteins ABHD5, PGRMC1 and squalene synthase can serve as novel immunohistochemical markers for sebaceous neoplasms and differentiate sebaceous carcinoma from sebaceoma and basal cell carcinoma with clear cell features. Journal of cutaneous pathology 21 23557589
2022 PGRMC1 Regulates Cellular Senescence via Modulating FOXO1 Expression in Decidualizing Endometrial Stromal Cells. Biomolecules 20 36008941
2020 Novel nonclassic progesterone receptor PGRMC1 pulldown-precipitated proteins reveal a key role during human decidualization. Fertility and sterility 20 32386616
2015 May progesterone receptor membrane component 1 (PGRMC1) predict the risk of breast cancer? Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 20 26303031
2019 Progestogens and PGRMC1-dependent breast cancer tumor growth: An in-vitro and xenograft study. Maturitas 19 31027671
2020 PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease. BMC molecular and cell biology 18 32293262
2018 PGRMC1 localization and putative function in the nucleolus of bovine granulosa cells and oocytes. Reproduction (Cambridge, England) 17 29339453
2018 Function and structural regulation of the carbon monoxide (CO)-responsive membrane protein PGRMC1. Journal of clinical biochemistry and nutrition 17 30087538
2021 Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses. Cancers 16 34069911
2020 PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells. International journal of molecular sciences 16 33076541
2019 Role of PGRMC1 in cell physiology of cervical cancer. Life sciences 16 31216441
2019 Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with recurrent miscarriages. European journal of obstetrics, gynecology, and reproductive biology 15 31891895
2015 Hyaluronic acid prevents immunosuppressive drug-induced ovarian damage via up-regulating PGRMC1 expression. Scientific reports 15 25558795
2023 PGRMC1 promotes triple-negative breast cancer cell growth via suppressing ferroptosis. Climacteric : the journal of the International Menopause Society 14 36724820
2021 AG-205 Upregulates Enzymes Involved in Cholesterol Biosynthesis and Steroidogenesis in Human Endometrial Cells Independently of PGRMC1 and Related MAPR Proteins. Biomolecules 14 34680104
2022 Metastasis enhancer PGRMC1 boosts store-operated Ca2+ entry by uncoiling Ca2+ sensor STIM1 for focal adhesion turnover and actomyosin formation. Cell reports 13 35045297
2016 Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro. BioMed research international 13 27340667
2021 Deciphering the Role of PGRMC1 During Human Decidualization Using an In Vitro Approach. The Journal of clinical endocrinology and metabolism 12 33955452
2021 Clozapine Induced Disturbances in Hepatic Glucose Metabolism: The Potential Role of PGRMC1 Signaling. Frontiers in endocrinology 11 34970218
2020 Association of circulating Progesterone Receptor Membrane Component-1 (PGRMC1) with PGRMC1 expression in breast tumour tissue and with clinical breast tumour characteristics. Maturitas 11 32972637
2023 Progesterone Receptor Membrane Component 1 (PGRMC1) Modulates Tumour Progression, the Immune Microenvironment and the Response to Therapy in Glioblastoma. Cells 10 37887342
2023 New Insights on the Progesterone (P4) and PGRMC1/NENF Complex Interactions in Colorectal Cancer Progression. Cancers 10 37894441
2020 PGRMC1 in animal breast cancer tissue and blood is associated with increased tumor growth with norethisterone in contrast to progesterone and dydrogesterone: four-arm randomized placebo-controlled xenograft study. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 10 32208774
2025 Liver-specific gene PGRMC1 blocks c-Myc-induced hepatocarcinogenesis through ER stress-independent PERK activation. Nature communications 9 39747098
2023 PGRMC1 Ablation Protects from Energy-Starved Heart Failure by Promoting Fatty Acid/Pyruvate Oxidation. Cells 9 36899888
2023 Olanzapine-induced nonalcoholic fatty liver disease: The effects of differential food pattern and the involvement of PGRMC1 signaling. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 9 37019375
2021 MicroRNA-181a suppresses norethisterone-promoted tumorigenesis of breast epithelial MCF10A cells through the PGRMC1/EGFR-PI3K/Akt/mTOR signaling pathway. Translational oncology 9 33730679
2019 Epitope mapping of anti-PGRMC1 antibodies reveals the non-conventional membrane topology of PGRMC1 on the cell surface. Scientific reports 9 30679694
2019 PGRMC1 can trigger estrogen-dependent proliferation of breast cancer cells: estradiol vs. equilin vs. ethinylestradiol. Climacteric : the journal of the International Menopause Society 9 30862292
2022 E2 + norethisterone promotes the PI3K-AKT pathway via PGRMC1 to induce breast cancer cell proliferation. Climacteric : the journal of the International Menopause Society 8 35137666
2021 The ER transmembrane protein PGRMC1 recruits misfolded proteins for reticulophagic clearance. Autophagy 8 34779709
2018 Triple A patient cells suffering from mitotic defects fail to localize PGRMC1 to mitotic kinetochore fibers. Cell division 8 30455725
2024 Progesterone-mediated remodeling of the maternal-fetal interface by a PGRMC1-dependent mechanism. Journal of reproductive immunology 7 38555747
2021 A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract. European journal of human genetics : EJHG 7 33867527
2015 Progesterone Receptor Membrane Component 1 (PGRMC1) Expression in Murine Retina. Current eye research 7 26642738