{"gene":"PAQR7","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2018,"finding":"PAQR7 (mPRα) mediates rapid progesterone-induced relaxation of human umbilical vein vascular smooth muscle cells (VSMCs) through Gi protein coupling, leading to decreased cAMP, activation of MAP kinase/ERK and Akt/PI3K pathways, and reduced myosin light chain phosphorylation. These effects were blocked by pertussis toxin, mPRα siRNA knockdown, and pathway-specific inhibitors, but not by nuclear PR agonist R5020 or nPR siRNA.","method":"Collagen gel disk contraction assay, endothelium-denuded artery ring tension assay, siRNA knockdown, pertussis toxin treatment, pharmacological inhibitors (AZD6244, wortmannin, 8-Br-cAMP)","journal":"Molecular and cellular endocrinology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal functional assays (two contraction assays), reciprocal siRNA knockdown of mPRα vs nPR, pathway inhibitors, selective agonist 02-0; replicated across assays in single rigorous study","pmids":["29428395"],"is_preprint":false},{"year":2019,"finding":"mPRα (PAQR7) mediates progesterone-induced decrease in cytosolic Ca2+ in human umbilical artery VSMCs via Gi protein activation, downregulation of cAMP, inhibition of MAPK/Akt signaling, and decreased RhoA/ROCK activity. Knockdown of mPRα (but not nuclear PR) abolished these effects; pertussis toxin, 8-Br-cAMP, MAPK inhibitor PD98059, and Akt inhibitor ML-9 all blocked progesterone-induced Ca2+ decrease and VSMC relaxation.","method":"Intracellular Ca2+ measurement, siRNA knockdown, pertussis toxin treatment, pharmacological inhibitors, RhoA activity assay","journal":"Journal of molecular endocrinology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Ca2+ imaging, RhoA assay, selective agonist, siRNA knockdown vs nPR knockdown), consistent mechanistic pathway delineation in single rigorous study","pmids":["31416049"],"is_preprint":false},{"year":2021,"finding":"mPRα (PAQR7)-mediated progesterone signaling in VSMCs involves upregulation of SERCA2 protein expression and phospholamban (PLB) phosphorylation (disinhibiting SERCA), leading to increased Ca2+ uptake into the SR and VSMC relaxation. These effects required Gi, MAP kinase, Akt/PI3K signaling, and RhoA downregulation; SERCA2 siRNA knockdown or CPA (SERCA inhibitor) blocked progesterone-induced relaxation.","method":"SERCA2 siRNA knockdown, pharmacological inhibitors (CPA, NF023, AZD6244, wortmannin, calpeptin), SR Ca2+ measurement, immunoblotting for PLB phosphorylation","journal":"American journal of physiology. Endocrinology and metabolism","confidence":"High","confidence_rationale":"Tier 2 / Strong — siRNA knockdown of SERCA2, multiple pharmacological inhibitors, direct Ca2+ measurements, mPRα-selective agonist used throughout; multiple orthogonal methods in one rigorous study","pmids":["33427050"],"is_preprint":false},{"year":2022,"finding":"Homology modeling of mPRα (PAQR7) based on AdipoR1 crystal structure revealed: (1) intracellular N-terminus membrane orientation; (2) a zinc-binding pocket homologous to AdipoRs; (3) a critical H-bond between Q206 and the 20-carbonyl of progesterone. Mutational analysis showed complete loss of [3H]-progesterone binding in Q206R and V146S mutants. High Zn2+ concentrations restored progesterone binding in Q206R mutant, consistent with competitive displacement of oleic acid from the binding pocket. AdipoRon bound mPRα and mimicked progesterone signaling; D-e-MAPP blocked progesterone signaling.","method":"Homology modeling (AdipoR1 X-ray as template), site-directed mutagenesis, [3H]-progesterone radioligand binding assay, pharmacological assays","journal":"The Journal of steroid biochemistry and molecular biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — mutagenesis plus radioligand binding assay validates model predictions; homology model (not direct structure), single lab","pmids":["35189329"],"is_preprint":false},{"year":2022,"finding":"A steroid binding assay using graphene quantum dot-conjugated mPRα (GQD-mPRα) demonstrated direct ligand-receptor binding between mPRα and progesterone-BSA-FITC, with competition by free progesterone, confirming mPRα has a functional progesterone binding site.","method":"Fluorescence-based competitive binding assay using GQD-conjugated mPRα protein and progesterone-BSA-FITC","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct in vitro binding assay with competition, but single method, single lab","pmids":["35007844"],"is_preprint":false},{"year":2023,"finding":"mPRα (PAQR7) mediates neuroprotective effects of progesterone against 6-OHDA and MPP+ toxicity in SH-SY5Y cells (Parkinson's disease model). The mPR-selective agonist Org OD 02-0 was effective while nuclear PR agonist R5020 and GABAA agonist muscimol were not. mPRα siRNA knockdown abolished neuroprotection. PI3K-AKT and MAP kinase signaling pathways are involved in mPRα-mediated neuroprotection.","method":"siRNA knockdown of mPRα isoforms, selective pharmacological agonists (Org OD 02-0 vs R5020 vs muscimol), cell viability assays, pathway inhibitors","journal":"Frontiers in endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown combined with selective agonists and pathway inhibitors; single lab, multiple orthogonal approaches","pmids":["36967764"],"is_preprint":false},{"year":2021,"finding":"mPRα (PAQR7) activation in Schwann cell-like adipose stem cells (SCL-ASC) promotes cell migration, differentiation, morphology changes, and BDNF release. mPRα localization changed upon activation. Src and PI3K-Akt signaling pathways are required for mPRα activity in SCL-ASC. mPRα siRNA confirmed this isoform is responsible.","method":"siRNA knockdown of mPRα, selective mPR agonist Org OD 02-0, cell migration assays, BDNF ELISA, pathway inhibitors, immunofluorescence for localization","journal":"Molecular and cellular endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown, selective agonist, multiple functional readouts, subcellular localization; single lab","pmids":["33930460"],"is_preprint":false},{"year":2022,"finding":"mPRα (PAQR7) activation in Schwann cell-like adipose stem cells (SCL-ASC) promotes neurite outgrowth in co-cultured neuronal cells (IMR-32 and SH-SY5Y) through SCL-ASC-dependent release of BDNF and IGF-2, while direct mPRα activation on neuronal cells promotes cell survival. mPRα siRNA in SCL-ASC abolished the neurite outgrowth effect.","method":"Conditioned medium experiments, co-culture, siRNA knockdown of mPRα in SCL-ASC, selective agonist Org OD 02-0, BDNF/IGF-2 measurements","journal":"Journal of molecular neuroscience : MN","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown, conditioned medium, co-culture, and direct agonist approaches; single lab, multiple orthogonal methods","pmids":["35974286"],"is_preprint":false},{"year":2024,"finding":"PAQR7 deficiency in KGN granulosa cells increased apoptosis, which was rescued by P4 supplementation. Paqr7 knockout female mice showed prolonged estrous cycles, reduced follicular growth, increased atresia follicles, decreased E2 and AMH, reduced litter sizes, and impaired spontaneous ovulation. The anti-apoptotic mechanism involves the BCL-2/BAX/CASPASE-3 signaling pathway.","method":"siPAQR7 knockdown in KGN cells, Paqr7 knockout mouse model, follicle counting, hormone measurements, apoptosis assays, western blot for BCL-2/BAX/CASPASE-3","journal":"Journal of ovarian research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mouse model plus cell-based siRNA knockdown, multiple reproductive phenotype readouts, pathway analysis; single lab","pmids":["38317224"],"is_preprint":false},{"year":2016,"finding":"A Paqr7 structural homolog (Paqr7b) in half-smooth tongue sole fish ovary is required for progestin-induced oocyte maturation. Morpholino antisense knockdown of Paqr7b in oocytes blocked progestin-induced maturation. Paqr7b expression in oocytes and pituitary was regulated by gonadotropin in a dose- and stage-dependent manner.","method":"Morpholino antisense oligonucleotide microinjection in oocytes, in situ hybridization, immunohistochemistry, cDNA cloning and phylogenetic analysis","journal":"General and comparative endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — morpholino knockdown with direct functional readout (oocyte maturation); fish ortholog/paralog, single lab","pmids":["27554928"],"is_preprint":false},{"year":2025,"finding":"2-Hydroxypentanoic acid (2-HPA) from marine algae Padina shows competitive binding to human mPRα (PAQR7) in a GQD-mPRα binding assay and inhibits fish oocyte maturation and ovulation in vivo. Both S- and R-stereoisomers showed equal activity. Structural analogues of 2-HPA lacked competitive binding, indicating structural specificity. 2-HPA acts as a novel mPRα antagonist.","method":"GQD-mPRα competitive binding assay, goldfish oocyte maturation assay in vitro, zebrafish ovulation assay in vivo","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — binding assay plus functional assay in fish model; novel finding but single lab, single paper","pmids":["39922053"],"is_preprint":false},{"year":2004,"finding":"PGLP (an alias for PAQR7) was identified as a PPARgamma1-target gene encoding a 38 kDa cytoplasmic membranous protein that is dramatically induced in mouse liver following PPARgamma1 overexpression (adenoviral approach) but not by fasting or choline deficiency-induced fatty liver. Full-length cDNA was cloned.","method":"Affymetrix microarray, adenoviral PPARgamma1 overexpression in PPARalpha-deficient mouse liver, cDNA cloning, northern blot","journal":"Biochimie","confidence":"Low","confidence_rationale":"Tier 3 / Weak — gene expression induction identified by microarray with validation; no mechanistic functional characterization of the PGLP/PAQR7 protein itself","pmids":["15589683"],"is_preprint":false}],"current_model":"PAQR7 (mPRα) is a 7-transmembrane membrane progesterone receptor with an intracellular N-terminus and a zinc-containing ligand-binding pocket (homologous to AdipoRs) where progesterone binds via a critical H-bond to Q206; upon progesterone binding, it couples to inhibitory G proteins (Gi) to decrease cAMP, activate MAP kinase/ERK and Akt/PI3K pathways, downregulate RhoA/ROCK and Ca2+ channel activity, upregulate SERCA2/phospholamban function, and reduce myosin light chain phosphorylation, collectively inducing vascular smooth muscle relaxation; in reproductive cells it mediates anti-apoptotic signaling through BCL-2/BAX/CASPASE-3, in neural/Schwann cells it promotes survival, migration, and BDNF/IGF-2 release via Src and PI3K-Akt, and in granulosa cells it supports ovarian follicle development and oocyte maturation."},"narrative":{"mechanistic_narrative":"PAQR7 (mPRα) is a membrane progesterone receptor that transduces rapid, non-genomic progesterone signaling through inhibitory G protein (Gi) coupling, with prominent roles in vascular smooth muscle relaxation, neural cell survival, and ovarian follicle development [PMID:29428395, PMID:36967764, PMID:38317224]. In human vascular smooth muscle cells, progesterone acting through mPRα—but not the nuclear progesterone receptor—couples to Gi to lower cAMP, activate MAP kinase/ERK and Akt/PI3K signaling, and reduce myosin light chain phosphorylation, producing relaxation [PMID:29428395]. This pathway lowers cytosolic Ca2+ by downregulating RhoA/ROCK activity [PMID:31416049] and by upregulating SERCA2 expression and phospholamban phosphorylation to drive Ca2+ uptake into the sarcoplasmic reticulum [PMID:33427050]. Ligand recognition occurs through a zinc-containing pocket modeled on the adiponectin receptors, in which a hydrogen bond between Q206 and the progesterone 20-carbonyl is essential for binding; mutation of Q206 or V146 abolishes progesterone binding, and the AdipoR agonist AdipoRon mimics progesterone signaling at the receptor [PMID:35189329, PMID:35007844]. Beyond the vasculature, mPRα mediates progesterone neuroprotection in dopaminergic cell models via PI3K-AKT and MAP kinase pathways [PMID:36967764], drives Schwann cell-like adipose stem cell migration, differentiation, and BDNF/IGF-2 release through Src and PI3K-Akt signaling to support neurite outgrowth and neuronal survival [PMID:33930460, PMID:35974286], and protects granulosa cells from apoptosis via BCL-2/BAX/CASPASE-3 signaling, with Paqr7 knockout mice showing impaired follicular growth, ovulation, and fertility [PMID:38317224].","teleology":[{"year":2004,"claim":"Before functional characterization, the question was whether PAQR7 (then PGLP) was a regulated gene of defined tissue context; it was placed downstream of PPARgamma1 as an inducible cytoplasmic membranous protein.","evidence":"Affymetrix microarray and adenoviral PPARgamma1 overexpression in mouse liver with cDNA cloning","pmids":["15589683"],"confidence":"Low","gaps":["No mechanistic function assigned to the protein","Link to progesterone signaling not yet established","Single transcriptional induction observation"]},{"year":2016,"claim":"To test whether PAQR-family membrane progesterone receptors are functionally required for reproduction, a tongue sole homolog was knocked down, establishing a role in progestin-induced oocyte maturation.","evidence":"Morpholino knockdown in fish oocytes with in situ hybridization and gonadotropin regulation analysis","pmids":["27554928"],"confidence":"Medium","gaps":["Fish ortholog/paralog, not human PAQR7","Downstream signaling pathway not delineated","Receptor-ligand binding not directly shown"]},{"year":2018,"claim":"The central question of how progesterone produces rapid vascular effects was answered by showing mPRα couples to Gi to relax vascular smooth muscle independently of the nuclear receptor.","evidence":"Collagen gel and artery ring contraction assays, reciprocal mPRα vs nPR siRNA knockdown, pertussis toxin, and pathway inhibitors in human VSMCs","pmids":["29428395"],"confidence":"High","gaps":["Direct receptor-G protein interaction not structurally resolved","In vivo vascular relevance not tested"]},{"year":2019,"claim":"Building on Gi coupling, the downstream effector arm was defined by showing mPRα lowers cytosolic Ca2+ through cAMP and MAPK/Akt downregulation and decreased RhoA/ROCK activity.","evidence":"Intracellular Ca2+ imaging, RhoA activity assay, siRNA knockdown, and pathway inhibitors in human umbilical artery VSMCs","pmids":["31416049"],"confidence":"High","gaps":["Connection between RhoA downregulation and Ca2+ handling not fully resolved","Membrane proximal events between receptor and RhoA unmapped"]},{"year":2021,"claim":"The Ca2+-lowering mechanism was mechanistically completed by identifying SERCA2 upregulation and phospholamban phosphorylation as the effectors driving SR Ca2+ uptake and relaxation.","evidence":"SERCA2 siRNA knockdown, SERCA inhibitor CPA, SR Ca2+ measurement, and immunoblotting for PLB phosphorylation","pmids":["33427050"],"confidence":"High","gaps":["Mechanism linking PI3K/Akt to PLB phosphorylation not defined","SERCA2 transcriptional vs post-translational induction not separated"]},{"year":2021,"claim":"To extend mPRα beyond vasculature, its activation in Schwann cell-like adipose stem cells was shown to promote migration, differentiation, and BDNF release via Src and PI3K-Akt.","evidence":"siRNA knockdown, selective agonist Org OD 02-0, migration assays, BDNF ELISA, and immunofluorescence localization","pmids":["33930460"],"confidence":"Medium","gaps":["Mechanism of agonist-induced relocalization unknown","Direct Src activation by the receptor not shown"]},{"year":2022,"claim":"The molecular basis of ligand recognition was addressed by homology modeling and mutagenesis, defining a zinc-containing pocket and an essential Q206 hydrogen bond to progesterone.","evidence":"AdipoR1-based homology model, site-directed mutagenesis (Q206R, V146S), [3H]-progesterone radioligand binding, and AdipoRon/D-e-MAPP pharmacology","pmids":["35189329"],"confidence":"Medium","gaps":["No experimental structure of PAQR7","Single lab; model-based predictions","Zinc stoichiometry and catalytic relevance not established"]},{"year":2022,"claim":"Direct ligand binding was independently confirmed using a graphene quantum dot-conjugated receptor assay showing competitive progesterone binding.","evidence":"Fluorescence-based competitive binding with GQD-mPRα and progesterone-BSA-FITC","pmids":["35007844"],"confidence":"Medium","gaps":["Single method, single lab","Binding affinity and kinetics not quantified"]},{"year":2022,"claim":"The neural role was broadened by showing mPRα-activated SCL-ASCs promote neurite outgrowth in neurons via secreted BDNF and IGF-2, while direct neuronal mPRα activation promotes survival.","evidence":"Conditioned medium, co-culture, siRNA knockdown in SCL-ASC, selective agonist, and BDNF/IGF-2 measurement","pmids":["35974286"],"confidence":"Medium","gaps":["Paracrine vs direct contributions in vivo unquantified","Signaling linking mPRα to BDNF/IGF-2 secretion not mapped"]},{"year":2023,"claim":"Whether mPRα mediates progesterone neuroprotection was tested in a Parkinson's disease cell model, showing selective mPR agonism protects against neurotoxins via PI3K-AKT and MAP kinase.","evidence":"siRNA knockdown, selective agonist Org OD 02-0 vs R5020 vs muscimol, viability assays, and pathway inhibitors in SH-SY5Y cells","pmids":["36967764"],"confidence":"Medium","gaps":["No in vivo neuroprotection demonstrated","Downstream survival effectors not identified"]},{"year":2024,"claim":"The reproductive requirement for PAQR7 in mammals was established, linking its anti-apoptotic BCL-2/BAX/CASPASE-3 signaling to follicle development and fertility.","evidence":"siPAQR7 in KGN granulosa cells with P4 rescue, Paqr7 knockout mice, follicle counts, hormone measurements, and apoptosis pathway western blots","pmids":["38317224"],"confidence":"Medium","gaps":["Coupling between receptor and BCL-2/BAX regulation not delineated","Single lab; granulosa-specific vs systemic contributions not separated"]},{"year":2025,"claim":"Pharmacological tractability of the ligand pocket was probed by identifying 2-HPA as a competitive natural antagonist with structural specificity.","evidence":"GQD-mPRα competitive binding assay, goldfish oocyte maturation, and zebrafish ovulation assays","pmids":["39922053"],"confidence":"Low","gaps":["Single lab, single paper","Antagonism validated in fish, not human cells","No structural confirmation of binding site engagement"]},{"year":null,"claim":"How mPRα physically engages Gi at the membrane and how a single receptor selects between vascular relaxation, neuroprotective, and anti-apoptotic outputs in different cell types remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No experimental receptor structure or receptor-G protein complex","Cell-type-specific effector selection unexplained","In vivo vascular and neural functions largely untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[3,4]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[8]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[8,9]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86WK9","full_name":"Membrane progestin receptor alpha","aliases":["Membrane progesterone P4 receptor alpha","Membrane progesterone receptor alpha","Progesterone and adipoQ receptor family member 7","Progestin and adipoQ receptor family member 7","Progestin and adipoQ receptor family member VII"],"length_aa":346,"mass_kda":39.7,"function":"Plasma membrane progesterone (P4) receptor coupled to G proteins (PubMed:23763432). Seems to act through a G(i) mediated pathway (PubMed:23763432). May be involved in oocyte maturation (PubMed:12601167). Involved in neurosteroid inhibition of apoptosis (PubMed:23161870). Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone (PubMed:23161870)","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q86WK9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PAQR7","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CCDC47","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PAQR7","total_profiled":1310},"omim":[{"mim_id":"607779","title":"PROGESTIN AND ADIPOQ RECEPTOR FAMILY, MEMBER 7; PAQR7","url":"https://www.omim.org/entry/607779"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":60.1}],"url":"https://www.proteinatlas.org/search/PAQR7"},"hgnc":{"alias_symbol":["mSR","MPRA","PGLP"],"prev_symbol":[]},"alphafold":{"accession":"Q86WK9","domains":[{"cath_id":"-","chopping":"83-346","consensus_level":"high","plddt":93.027,"start":83,"end":346}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86WK9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86WK9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86WK9-F1-predicted_aligned_error_v6.png","plddt_mean":89.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PAQR7","jax_strain_url":"https://www.jax.org/strain/search?query=PAQR7"},"sequence":{"accession":"Q86WK9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86WK9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86WK9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86WK9"}},"corpus_meta":[{"pmid":"35516490","id":"PMC_35516490","title":"Metabolic characterisation of Magnetospirillum gryphiswaldense MSR-1 using LC-MS-based metabolite profiling.","date":"2020","source":"RSC advances","url":"https://pubmed.ncbi.nlm.nih.gov/35516490","citation_count":113,"is_preprint":false},{"pmid":"8951791","id":"PMC_8951791","title":"Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis.","date":"1996","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/8951791","citation_count":110,"is_preprint":false},{"pmid":"10473142","id":"PMC_10473142","title":"Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ.","date":"1999","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/10473142","citation_count":109,"is_preprint":false},{"pmid":"15297499","id":"PMC_15297499","title":"Characterization and prevalence of MefA, MefE, and the associated msr(D) gene in Streptococcus pneumoniae clinical isolates.","date":"2004","source":"Journal of clinical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/15297499","citation_count":90,"is_preprint":false},{"pmid":"11744380","id":"PMC_11744380","title":"Expression of the murine msr/apj receptor and its ligand apelin is upregulated during formation of the retinal vessels.","date":"2002","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/11744380","citation_count":81,"is_preprint":false},{"pmid":"13678826","id":"PMC_13678826","title":"Msr(A) and related macrolide/streptogramin resistance determinants: incomplete transporters?","date":"2003","source":"International journal of antimicrobial agents","url":"https://pubmed.ncbi.nlm.nih.gov/13678826","citation_count":80,"is_preprint":false},{"pmid":"10734045","id":"PMC_10734045","title":"Dissociation of the high density lipoprotein and low density lipoprotein binding activities of murine scavenger receptor class B type I (mSR-BI) using retrovirus library-based activity dissection.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10734045","citation_count":79,"is_preprint":false},{"pmid":"17594464","id":"PMC_17594464","title":"Purified and sterilized magnetosomes from Magnetospirillum gryphiswaldense MSR-1 were not toxic to mouse fibroblasts in vitro.","date":"2007","source":"Letters in applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/17594464","citation_count":69,"is_preprint":false},{"pmid":"15060030","id":"PMC_15060030","title":"The PmlI-PmlR quorum-sensing system in Burkholderia pseudomallei plays a key role in virulence and modulates production of the MprA protease.","date":"2004","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/15060030","citation_count":68,"is_preprint":false},{"pmid":"15601704","id":"PMC_15601704","title":"Identification and characterization of a regulatory sequence recognized by Mycobacterium tuberculosis persistence regulator MprA.","date":"2005","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/15601704","citation_count":65,"is_preprint":false},{"pmid":"18639631","id":"PMC_18639631","title":"Ferrous iron transport protein B gene (feoB1) plays an accessory role in magnetosome formation in Magnetospirillum gryphiswaldense strain MSR-1.","date":"2008","source":"Research in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/18639631","citation_count":63,"is_preprint":false},{"pmid":"12670694","id":"PMC_12670694","title":"Characteristic expression of three genes, msr(A), mph(C) and erm(Y), that confer resistance to macrolide antibiotics on Staphylococcus aureus.","date":"2003","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/12670694","citation_count":59,"is_preprint":false},{"pmid":"12915314","id":"PMC_12915314","title":"The msr/apj gene encoding the apelin receptor is an early and specific marker of the venous phenotype in the retinal vasculature.","date":"2003","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/12915314","citation_count":58,"is_preprint":false},{"pmid":"21724877","id":"PMC_21724877","title":"Semicontinuous culture of Magnetospirillum gryphiswaldense MSR-1 cells in an autofermentor by nutrient-balanced and isosmotic feeding strategies.","date":"2011","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21724877","citation_count":58,"is_preprint":false},{"pmid":"18425510","id":"PMC_18425510","title":"High-yield growth and magnetosome formation by Magnetospirillum gryphiswaldense MSR-1 in an oxygen-controlled fermentor supplied solely with air.","date":"2008","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/18425510","citation_count":56,"is_preprint":false},{"pmid":"21821774","id":"PMC_21821774","title":"Components of the Rv0081-Rv0088 locus, which encodes a predicted formate hydrogenlyase complex, are coregulated by Rv0081, MprA, and DosR in Mycobacterium tuberculosis.","date":"2011","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/21821774","citation_count":49,"is_preprint":false},{"pmid":"9583348","id":"PMC_9583348","title":"The multiple roles of macrophage scavenger receptors (MSR) in vivo: resistance to atherosclerosis and susceptibility to infection in MSR knockout mice.","date":"1997","source":"Journal of atherosclerosis and thrombosis","url":"https://pubmed.ncbi.nlm.nih.gov/9583348","citation_count":42,"is_preprint":false},{"pmid":"2152912","id":"PMC_2152912","title":"mprA, an Escherichia coli gene that reduces growth-phase-dependent synthesis of microcins B17 and C7 and blocks osmoinduction of proU when cloned on a high-copy-number plasmid.","date":"1990","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/2152912","citation_count":40,"is_preprint":false},{"pmid":"22636767","id":"PMC_22636767","title":"FeoB2 Functions in magnetosome formation and oxidative stress protection in Magnetospirillum gryphiswaldense strain MSR-1.","date":"2012","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/22636767","citation_count":40,"is_preprint":false},{"pmid":"1840583","id":"PMC_1840583","title":"Nucleotide sequence of the Escherichia coli regulatory gene mprA and construction and characterization of mprA-deficient mutants.","date":"1991","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/1840583","citation_count":39,"is_preprint":false},{"pmid":"11338182","id":"PMC_11338182","title":"Uptake of fibrillar beta-amyloid by microglia isolated from MSR-A (type I and type II) knockout mice.","date":"2001","source":"Neuroreport","url":"https://pubmed.ncbi.nlm.nih.gov/11338182","citation_count":38,"is_preprint":false},{"pmid":"25538698","id":"PMC_25538698","title":"Nucleotide sequence of conjugative prophage Φ1207.3 (formerly Tn1207.3) carrying the mef(A)/msr(D) genes for efflux resistance to macrolides in Streptococcus pyogenes.","date":"2014","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25538698","citation_count":37,"is_preprint":false},{"pmid":"16495276","id":"PMC_16495276","title":"Staphylococcus efflux msr(A) gene characterized in Streptococcus, Enterococcus, Corynebacterium, and Pseudomonas isolates.","date":"2006","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/16495276","citation_count":36,"is_preprint":false},{"pmid":"25695510","id":"PMC_25695510","title":"Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elements.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25695510","citation_count":35,"is_preprint":false},{"pmid":"23261969","id":"PMC_23261969","title":"Functional interplay between the ATP binding cassette Msr(D) protein and the membrane facilitator superfamily Mef(E) transporter for macrolide resistance in Escherichia coli.","date":"2012","source":"Research in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23261969","citation_count":33,"is_preprint":false},{"pmid":"33479888","id":"PMC_33479888","title":"Effects of Long-Term Exposure to Copper on the Keap1/Nrf2 Signaling Pathway and Msr-Related Redox Status in the Kidneys of Rats.","date":"2021","source":"Biological trace element research","url":"https://pubmed.ncbi.nlm.nih.gov/33479888","citation_count":31,"is_preprint":false},{"pmid":"31291895","id":"PMC_31291895","title":"Optimized PCR conditions minimizing the formation of chimeric DNA molecules from MPRA plasmid libraries.","date":"2019","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/31291895","citation_count":31,"is_preprint":false},{"pmid":"26531240","id":"PMC_26531240","title":"Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes.","date":"2015","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/26531240","citation_count":30,"is_preprint":false},{"pmid":"38275641","id":"PMC_38275641","title":"Role of Oxidative Stress, Methionine Oxidation and Methionine Sulfoxide Reductases (MSR) in Alzheimer's Disease.","date":"2023","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/38275641","citation_count":29,"is_preprint":false},{"pmid":"20674739","id":"PMC_20674739","title":"mamO and mamE genes are essential for magnetosome crystal biomineralization in Magnetospirillum gryphiswaldense MSR-1.","date":"2010","source":"Research in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/20674739","citation_count":29,"is_preprint":false},{"pmid":"15589683","id":"PMC_15589683","title":"Identification of promethin and PGLP as two novel up-regulated genes in PPARgamma1-induced adipogenic mouse liver.","date":"2004","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/15589683","citation_count":28,"is_preprint":false},{"pmid":"23333385","id":"PMC_23333385","title":"Regulation of MSR-1 and CD36 in macrophages by LOX-1 mediated through PPAR-γ.","date":"2013","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/23333385","citation_count":27,"is_preprint":false},{"pmid":"29028988","id":"PMC_29028988","title":"QuASAR-MPRA: accurate allele-specific analysis for massively parallel reporter assays.","date":"2018","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/29028988","citation_count":26,"is_preprint":false},{"pmid":"31775527","id":"PMC_31775527","title":"Methionine sulfoxide reductase (Msr) dysfunction in human brain disease.","date":"2019","source":"Free radical research","url":"https://pubmed.ncbi.nlm.nih.gov/31775527","citation_count":23,"is_preprint":false},{"pmid":"29428395","id":"PMC_29428395","title":"Progesterone induces relaxation of human umbilical cord vascular smooth muscle cells through mPRα (PAQR7).","date":"2018","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/29428395","citation_count":21,"is_preprint":false},{"pmid":"16431859","id":"PMC_16431859","title":"Molecular epidemiology of macrolide resistance in beta-haemolytic streptococci of Lancefield groups A, B, C and G and evidence for a new mef element in group G streptococci that carries allelic variants of mef and msr(D).","date":"2006","source":"The Journal of antimicrobial chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/16431859","citation_count":21,"is_preprint":false},{"pmid":"29864580","id":"PMC_29864580","title":"Development of a simple intensified fermentation strategy for growth of Magnetospirillum gryphiswaldense MSR-1: Physiological responses to changing environmental conditions.","date":"2018","source":"New biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/29864580","citation_count":21,"is_preprint":false},{"pmid":"33427050","id":"PMC_33427050","title":"Involvement of sarco/endoplasmic reticulum Ca2-ATPase (SERCA) in mPRα (PAQR7)-mediated progesterone induction of vascular smooth muscle relaxation.","date":"2021","source":"American journal of physiology. Endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/33427050","citation_count":19,"is_preprint":false},{"pmid":"35189329","id":"PMC_35189329","title":"Molecular modeling, mutational analysis and steroid specificity of the ligand binding pocket of mPRα (PAQR7): Shared ligand binding with AdipoR1 and its structural basis.","date":"2022","source":"The Journal of steroid biochemistry and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/35189329","citation_count":19,"is_preprint":false},{"pmid":"23937222","id":"PMC_23937222","title":"Expression patterns of key iron and oxygen metabolism genes during magnetosome formation in Magnetospirillum gryphiswaldense MSR-1.","date":"2013","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/23937222","citation_count":19,"is_preprint":false},{"pmid":"31416049","id":"PMC_31416049","title":"Role of mPRα (PAQR7) in progesterone-induced Ca2+ decrease in human vascular smooth muscle cells.","date":"2019","source":"Journal of molecular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/31416049","citation_count":18,"is_preprint":false},{"pmid":"38365907","id":"PMC_38365907","title":"Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38365907","citation_count":17,"is_preprint":false},{"pmid":"28584275","id":"PMC_28584275","title":"Physiological characteristics of Magnetospirillum gryphiswaldense MSR-1 that control cell growth under high-iron and low-oxygen conditions.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28584275","citation_count":17,"is_preprint":false},{"pmid":"27043321","id":"PMC_27043321","title":"Transcriptome analysis reveals physiological characteristics required for magnetosome formation in Magnetospirillum gryphiswaldense MSR-1.","date":"2016","source":"Environmental microbiology reports","url":"https://pubmed.ncbi.nlm.nih.gov/27043321","citation_count":17,"is_preprint":false},{"pmid":"26386052","id":"PMC_26386052","title":"Iron response regulator protein IrrB in Magnetospirillum gryphiswaldense MSR-1 helps control the iron/oxygen balance, oxidative stress tolerance, and magnetosome formation.","date":"2015","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/26386052","citation_count":17,"is_preprint":false},{"pmid":"29406792","id":"PMC_29406792","title":"Functional Predominance of msr(D), Which Is More Effective as mef(A)-Associated Than mef(E)-Associated, Over mef(A)/mef(E) in Macrolide Resistance in Streptococcus pyogenes.","date":"2018","source":"Microbial drug resistance (Larchmont, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/29406792","citation_count":17,"is_preprint":false},{"pmid":"34904889","id":"PMC_34904889","title":"Time-Sensitive Aspects of Mars Sample Return (MSR) Science.","date":"2022","source":"Astrobiology","url":"https://pubmed.ncbi.nlm.nih.gov/34904889","citation_count":16,"is_preprint":false},{"pmid":"23243303","id":"PMC_23243303","title":"Two bifunctional enzymes with ferric reduction ability play complementary roles during magnetosome synthesis in Magnetospirillum gryphiswaldense MSR-1.","date":"2012","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/23243303","citation_count":16,"is_preprint":false},{"pmid":"24020498","id":"PMC_24020498","title":"MamX encoded by the mamXY operon is involved in control of magnetosome maturation in Magnetospirillum gryphiswaldense MSR-1.","date":"2013","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/24020498","citation_count":16,"is_preprint":false},{"pmid":"36967764","id":"PMC_36967764","title":"Progesterone exerts a neuroprotective action in a Parkinson's disease human cell model through membrane progesterone receptor α (mPRα/PAQR7).","date":"2023","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/36967764","citation_count":15,"is_preprint":false},{"pmid":"7770037","id":"PMC_7770037","title":"Developmental and pathogen-induced activation of an msr gene, str 246C, from tobacco involves multiple regulatory elements.","date":"1995","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/7770037","citation_count":15,"is_preprint":false},{"pmid":"17534559","id":"PMC_17534559","title":"A novel ferric reductase purified from Magnetospirillum gryphiswaldense MSR-1.","date":"2007","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/17534559","citation_count":15,"is_preprint":false},{"pmid":"33468141","id":"PMC_33468141","title":"Fusion expression of nanobodies specific for the insecticide fipronil on magnetosomes in Magnetospirillum gryphiswaldense MSR-1.","date":"2021","source":"Journal of nanobiotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/33468141","citation_count":15,"is_preprint":false},{"pmid":"33930460","id":"PMC_33930460","title":"Membrane progesterone receptor α (mPRα/PAQR7) promotes migration, proliferation and BDNF release in human Schwann cell-like differentiated adipose stem cells.","date":"2021","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/33930460","citation_count":14,"is_preprint":false},{"pmid":"28461341","id":"PMC_28461341","title":"PGLP-1, a novel long-acting dual-function GLP-1 analog, ameliorates streptozotocin-induced hyperglycemia and inhibits body weight loss.","date":"2017","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/28461341","citation_count":14,"is_preprint":false},{"pmid":"32122903","id":"PMC_32122903","title":"The Novel Macrolide Resistance Genes mef(D), msr(F), and msr(H) Are Present on Resistance Islands in Macrococcus canis, Macrococcus caseolyticus, and Staphylococcus aureus.","date":"2020","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/32122903","citation_count":14,"is_preprint":false},{"pmid":"17359446","id":"PMC_17359446","title":"Development and clinical evaluation of a PCR assay targeting the metalloprotease gene (mprA) of B. pseudomallei.","date":"2007","source":"Zoonoses and public health","url":"https://pubmed.ncbi.nlm.nih.gov/17359446","citation_count":14,"is_preprint":false},{"pmid":"35310676","id":"PMC_35310676","title":"MSR-RCNN: A Multi-Class Crop Pest Detection Network Based on a Multi-Scale Super-Resolution Feature Enhancement Module.","date":"2022","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/35310676","citation_count":14,"is_preprint":false},{"pmid":"18205608","id":"PMC_18205608","title":"Disruption of a fur-like gene inhibits magnetosome formation in Magnetospirillum gryphiswaldense MSR-1.","date":"2007","source":"Biochemistry. Biokhimiia","url":"https://pubmed.ncbi.nlm.nih.gov/18205608","citation_count":13,"is_preprint":false},{"pmid":"22869124","id":"PMC_22869124","title":"Crystallization and preliminary crystallographic analysis of the C-terminal domain of MamM, a magnetosome-associated protein from Magnetospirillum gryphiswaldense MSR-1.","date":"2012","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/22869124","citation_count":13,"is_preprint":false},{"pmid":"34217103","id":"PMC_34217103","title":"PAQR7: An intermediary mediating nongenomic progesterone action in female reproductive tissue.","date":"2021","source":"Reproductive biology","url":"https://pubmed.ncbi.nlm.nih.gov/34217103","citation_count":12,"is_preprint":false},{"pmid":"36278814","id":"PMC_36278814","title":"circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis.","date":"2022","source":"The Kaohsiung journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36278814","citation_count":12,"is_preprint":false},{"pmid":"34534559","id":"PMC_34534559","title":"A comprehensive assessment of the biocompatibility of Magnetospirillum gryphiswaldense MSR-1 bacterial magnetosomes in vitro and in vivo.","date":"2021","source":"Toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/34534559","citation_count":12,"is_preprint":false},{"pmid":"34581623","id":"PMC_34581623","title":"CircRNA-MSR Regulates LPS-Induced C28/I2 Chondrocyte Injury through miR-643/MAP2K6 Signaling Pathway.","date":"2021","source":"Cartilage","url":"https://pubmed.ncbi.nlm.nih.gov/34581623","citation_count":11,"is_preprint":false},{"pmid":"35007844","id":"PMC_35007844","title":"Establishment of a steroid binding assay for membrane progesterone receptor alpha (PAQR7) by using graphene quantum dots (GQDs).","date":"2022","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/35007844","citation_count":11,"is_preprint":false},{"pmid":"34904892","id":"PMC_34904892","title":"Planning Implications Related to Sterilization-Sensitive Science Investigations Associated with Mars Sample Return (MSR).","date":"2022","source":"Astrobiology","url":"https://pubmed.ncbi.nlm.nih.gov/34904892","citation_count":11,"is_preprint":false},{"pmid":"34823574","id":"PMC_34823574","title":"Predicted transmembrane proteins with homology to Mef(A) are not responsible for complementing mef(A) deletion in the mef(A)-msr(D) macrolide efflux system in Streptococcus pneumoniae.","date":"2021","source":"BMC research notes","url":"https://pubmed.ncbi.nlm.nih.gov/34823574","citation_count":10,"is_preprint":false},{"pmid":"30052913","id":"PMC_30052913","title":"Design tools for MPRA experiments.","date":"2018","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/30052913","citation_count":9,"is_preprint":false},{"pmid":"37298589","id":"PMC_37298589","title":"Genome-Wide Identification and Characterization of the Msr Gene Family in Alfalfa under Abiotic Stress.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37298589","citation_count":9,"is_preprint":false},{"pmid":"38071209","id":"PMC_38071209","title":"Pan msr gene deleted strain of Salmonella Typhimurium suffers oxidative stress, depicts macromolecular damage and attenuated virulence.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38071209","citation_count":9,"is_preprint":false},{"pmid":"27554928","id":"PMC_27554928","title":"Identification and characterization of a progestin and adipoQ receptor (PAQR) structurally related to Paqr7 in the ovary of Cynoglossus semilaevis and its potential role in regulating oocyte maturation.","date":"2016","source":"General and comparative endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/27554928","citation_count":9,"is_preprint":false},{"pmid":"37934249","id":"PMC_37934249","title":"Biosynthesis of magnetosome-nanobody complex in Magnetospirillum gryphiswaldense MSR-1 and a magnetosome-nanobody-based enzyme-linked immunosorbent assay for the detection of tetrabromobisphenol A in water.","date":"2023","source":"Analytical and bioanalytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37934249","citation_count":9,"is_preprint":false},{"pmid":"26429294","id":"PMC_26429294","title":"Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes.","date":"2015","source":"Diagnostic microbiology and infectious disease","url":"https://pubmed.ncbi.nlm.nih.gov/26429294","citation_count":9,"is_preprint":false},{"pmid":"30797225","id":"PMC_30797225","title":"Effects of Environmental Conditions on High-Yield Magnetosome Production by Magnetospirillum gryphiswaldense MSR-1.","date":"2019","source":"Iranian biomedical journal","url":"https://pubmed.ncbi.nlm.nih.gov/30797225","citation_count":9,"is_preprint":false},{"pmid":"17553479","id":"PMC_17553479","title":"A CBS haplotype and a polymorphism at the MSR gene are associated with cardiovascular disease in a Spanish case-control study.","date":"2007","source":"Clinical biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17553479","citation_count":8,"is_preprint":false},{"pmid":"35718158","id":"PMC_35718158","title":"Relevance of methionine sulfoxide reductase(s) (MSR) as candidate proteins in redox homeostasis-mediated resistance response to Helicoverpa armigera (Hübner) in the pigeonpea wild relative Cajanus platycarpus (Benth.) Maesen.","date":"2022","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/35718158","citation_count":8,"is_preprint":false},{"pmid":"26879571","id":"PMC_26879571","title":"A novel role for Crp in controlling magnetosome biosynthesis in Magnetospirillum gryphiswaldense MSR-1.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26879571","citation_count":7,"is_preprint":false},{"pmid":"28261169","id":"PMC_28261169","title":"The Disruption of an OxyR-Like Protein Impairs Intracellular Magnetite Biomineralization in Magnetospirillum gryphiswaldense MSR-1.","date":"2017","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28261169","citation_count":7,"is_preprint":false},{"pmid":"38317224","id":"PMC_38317224","title":"Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice.","date":"2024","source":"Journal of ovarian research","url":"https://pubmed.ncbi.nlm.nih.gov/38317224","citation_count":6,"is_preprint":false},{"pmid":"36625667","id":"PMC_36625667","title":"Streptococcus pyogenes Φ1207.3 Is a Temperate Bacteriophage Carrying the Macrolide Resistance Gene Pair mef(A)-msr(D) and Capable of Lysogenizing Different Streptococci.","date":"2023","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/36625667","citation_count":6,"is_preprint":false},{"pmid":"19024313","id":"PMC_19024313","title":"[Using MSR model to analyze the impact of gene-gene interaction with related to the genetic polymorphism of metabolism enzymes on the risk of breast cancer].","date":"2008","source":"Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/19024313","citation_count":6,"is_preprint":false},{"pmid":"19165516","id":"PMC_19165516","title":"A thiol-activated lipase from Trichosporon asahii MSR 54: detergent compatibility and presoak formulation for oil removal from soiled cloth at ambient temperature.","date":"2009","source":"Journal of industrial microbiology & biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/19165516","citation_count":6,"is_preprint":false},{"pmid":"25801573","id":"PMC_25801573","title":"ClpP-independent function of ClpX interferes with telithromycin resistance conferred by Msr(A) in Staphylococcus aureus.","date":"2015","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/25801573","citation_count":6,"is_preprint":false},{"pmid":"33574570","id":"PMC_33574570","title":"Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33574570","citation_count":5,"is_preprint":false},{"pmid":"34747464","id":"PMC_34747464","title":"Macrolides mediate transcriptional activation of the msr(E)-mph(E) operon through histone-like nucleoid-structuring protein (HNS) and cAMP receptor protein (CRP).","date":"2022","source":"The Journal of antimicrobial chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/34747464","citation_count":5,"is_preprint":false},{"pmid":"37645832","id":"PMC_37645832","title":"Characterization of enhancer activity in early human neurodevelopment using Massively parallel reporter assay (MPRA) and forebrain organoids.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37645832","citation_count":5,"is_preprint":false},{"pmid":"33118027","id":"PMC_33118027","title":"The novel macrolide resistance genes mef(F) and msr(G) are located on a plasmid in Macrococcus canis and a transposon in Macrococcus caseolyticus.","date":"2021","source":"The Journal of antimicrobial chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/33118027","citation_count":5,"is_preprint":false},{"pmid":"37214292","id":"PMC_37214292","title":"Evaluation of cell disruption technologies on magnetosome chain length and aggregation behaviour from Magnetospirillum gryphiswaldense MSR-1.","date":"2023","source":"Frontiers in bioengineering and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/37214292","citation_count":5,"is_preprint":false},{"pmid":"37088211","id":"PMC_37088211","title":"Hexavalent chromate bioreduction by a magnetotactic bacterium Magnetospirillum gryphiswaldense MSR-1 and the effect of magnetosome synthesis.","date":"2023","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/37088211","citation_count":5,"is_preprint":false},{"pmid":"35432273","id":"PMC_35432273","title":"Successful Intra- but Not Inter-species Recombination of msr(D) in Neisseria subflava.","date":"2022","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35432273","citation_count":4,"is_preprint":false},{"pmid":"30367002","id":"PMC_30367002","title":"Work Patterns of MamXY Proteins during Magnetosome Formation in Magnetospirillum gryphiswaldense MSR-1.","date":"2019","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30367002","citation_count":4,"is_preprint":false},{"pmid":"35646410","id":"PMC_35646410","title":"Methionine strengthens anti-inflammation of rice protein via depressing NF-κB activation and stimulating Msr expression in rats fed cholesterol-enriched diets.","date":"2022","source":"Food science and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/35646410","citation_count":4,"is_preprint":false},{"pmid":"31297108","id":"PMC_31297108","title":"Novel Protein Mg2046 Regulates Magnetosome Synthesis in Magnetospirillum gryphiswaldense MSR-1 by Modulating a Proper Redox Status.","date":"2019","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31297108","citation_count":4,"is_preprint":false},{"pmid":"30205970","id":"PMC_30205970","title":"Novel MprA binding motifs in the phoP regulatory region in Mycobacterium tuberculosis.","date":"2018","source":"Tuberculosis (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/30205970","citation_count":3,"is_preprint":false},{"pmid":"39425777","id":"PMC_39425777","title":"Assessing the effects of NapA gene overexpression on denitrification and denitrogenation in magnetospirillum gryphiswaldense MSR-1.","date":"2024","source":"Archives of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/39425777","citation_count":3,"is_preprint":false},{"pmid":"35974286","id":"PMC_35974286","title":"Membrane Progesterone Receptor α (mPRα/PAQR7) Promotes Survival and Neurite Outgrowth of Human Neuronal Cells by a Direct Action and Through Schwann Cell-like Stem Cells.","date":"2022","source":"Journal of molecular neuroscience : MN","url":"https://pubmed.ncbi.nlm.nih.gov/35974286","citation_count":3,"is_preprint":false},{"pmid":"20606283","id":"PMC_20606283","title":"Crystallization and preliminary crystallographic analysis of the Magnetospirillum magneticum AMB-1 and M. gryphiswaldense MSR-1 magnetosome-associated proteins MamA.","date":"2010","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/20606283","citation_count":3,"is_preprint":false},{"pmid":"34974869","id":"PMC_34974869","title":"OxyR-Like Improves Cell Hydrogen Peroxide Tolerance by Participating in Monocyte Chemotaxis and Oxidative Phosphorylation Regulation in Magnetospirillum Gryphiswaldense MSR-1.","date":"2021","source":"Journal of biomedical nanotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/34974869","citation_count":3,"is_preprint":false},{"pmid":"39922053","id":"PMC_39922053","title":"Discovery of specific activity of 2-hydroxypentanoic acid acting on the mPR alpha (Paqr7) from the marine algae Padina.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/39922053","citation_count":3,"is_preprint":false},{"pmid":"39952712","id":"PMC_39952712","title":"Bioinformatics of simultaneous, quantitative measurements of full-length tRNA and tRNA fragments by MSR sequencing.","date":"2024","source":"Methods in enzymology","url":"https://pubmed.ncbi.nlm.nih.gov/39952712","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":55137,"output_tokens":3936,"usd":0.112226,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11442,"output_tokens":3937,"usd":0.077817,"stage2_stop_reason":"end_turn"},"total_usd":0.190043,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about PAQR7 (also known as mPRα, MPRA, PGLP) - the human membrane progesterone receptor alpha, a member of the progestin and adipoQ receptor family.\n\nPapers clearly about PAQR7/mPRα: [35], [38], [39], [41], [50], [54], [61], [65], [71], [79], [96], [99]\nPaper [31] mentions PGLP as an alias but describes it as a PPARgamma-induced gene with no mechanistic detail about PAQR7 function.\n\nThe other papers are about: Magnetospirillum MSR-1 bacteria, macrolide resistance msr genes, scavenger receptors (MSR-A/MSR-B), methionine sulfoxide reductases (MsrA/MsrB), MPRA (massively parallel reporter assay), etc. - all symbol collisions or unrelated topics.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"PAQR7 (mPRα) mediates rapid progesterone-induced relaxation of human umbilical vein vascular smooth muscle cells (VSMCs) through Gi protein coupling, leading to decreased cAMP, activation of MAP kinase/ERK and Akt/PI3K pathways, and reduced myosin light chain phosphorylation. These effects were blocked by pertussis toxin, mPRα siRNA knockdown, and pathway-specific inhibitors, but not by nuclear PR agonist R5020 or nPR siRNA.\",\n      \"method\": \"Collagen gel disk contraction assay, endothelium-denuded artery ring tension assay, siRNA knockdown, pertussis toxin treatment, pharmacological inhibitors (AZD6244, wortmannin, 8-Br-cAMP)\",\n      \"journal\": \"Molecular and cellular endocrinology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal functional assays (two contraction assays), reciprocal siRNA knockdown of mPRα vs nPR, pathway inhibitors, selective agonist 02-0; replicated across assays in single rigorous study\",\n      \"pmids\": [\"29428395\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"mPRα (PAQR7) mediates progesterone-induced decrease in cytosolic Ca2+ in human umbilical artery VSMCs via Gi protein activation, downregulation of cAMP, inhibition of MAPK/Akt signaling, and decreased RhoA/ROCK activity. Knockdown of mPRα (but not nuclear PR) abolished these effects; pertussis toxin, 8-Br-cAMP, MAPK inhibitor PD98059, and Akt inhibitor ML-9 all blocked progesterone-induced Ca2+ decrease and VSMC relaxation.\",\n      \"method\": \"Intracellular Ca2+ measurement, siRNA knockdown, pertussis toxin treatment, pharmacological inhibitors, RhoA activity assay\",\n      \"journal\": \"Journal of molecular endocrinology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Ca2+ imaging, RhoA assay, selective agonist, siRNA knockdown vs nPR knockdown), consistent mechanistic pathway delineation in single rigorous study\",\n      \"pmids\": [\"31416049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"mPRα (PAQR7)-mediated progesterone signaling in VSMCs involves upregulation of SERCA2 protein expression and phospholamban (PLB) phosphorylation (disinhibiting SERCA), leading to increased Ca2+ uptake into the SR and VSMC relaxation. These effects required Gi, MAP kinase, Akt/PI3K signaling, and RhoA downregulation; SERCA2 siRNA knockdown or CPA (SERCA inhibitor) blocked progesterone-induced relaxation.\",\n      \"method\": \"SERCA2 siRNA knockdown, pharmacological inhibitors (CPA, NF023, AZD6244, wortmannin, calpeptin), SR Ca2+ measurement, immunoblotting for PLB phosphorylation\",\n      \"journal\": \"American journal of physiology. Endocrinology and metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — siRNA knockdown of SERCA2, multiple pharmacological inhibitors, direct Ca2+ measurements, mPRα-selective agonist used throughout; multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"33427050\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Homology modeling of mPRα (PAQR7) based on AdipoR1 crystal structure revealed: (1) intracellular N-terminus membrane orientation; (2) a zinc-binding pocket homologous to AdipoRs; (3) a critical H-bond between Q206 and the 20-carbonyl of progesterone. Mutational analysis showed complete loss of [3H]-progesterone binding in Q206R and V146S mutants. High Zn2+ concentrations restored progesterone binding in Q206R mutant, consistent with competitive displacement of oleic acid from the binding pocket. AdipoRon bound mPRα and mimicked progesterone signaling; D-e-MAPP blocked progesterone signaling.\",\n      \"method\": \"Homology modeling (AdipoR1 X-ray as template), site-directed mutagenesis, [3H]-progesterone radioligand binding assay, pharmacological assays\",\n      \"journal\": \"The Journal of steroid biochemistry and molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mutagenesis plus radioligand binding assay validates model predictions; homology model (not direct structure), single lab\",\n      \"pmids\": [\"35189329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"A steroid binding assay using graphene quantum dot-conjugated mPRα (GQD-mPRα) demonstrated direct ligand-receptor binding between mPRα and progesterone-BSA-FITC, with competition by free progesterone, confirming mPRα has a functional progesterone binding site.\",\n      \"method\": \"Fluorescence-based competitive binding assay using GQD-conjugated mPRα protein and progesterone-BSA-FITC\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct in vitro binding assay with competition, but single method, single lab\",\n      \"pmids\": [\"35007844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"mPRα (PAQR7) mediates neuroprotective effects of progesterone against 6-OHDA and MPP+ toxicity in SH-SY5Y cells (Parkinson's disease model). The mPR-selective agonist Org OD 02-0 was effective while nuclear PR agonist R5020 and GABAA agonist muscimol were not. mPRα siRNA knockdown abolished neuroprotection. PI3K-AKT and MAP kinase signaling pathways are involved in mPRα-mediated neuroprotection.\",\n      \"method\": \"siRNA knockdown of mPRα isoforms, selective pharmacological agonists (Org OD 02-0 vs R5020 vs muscimol), cell viability assays, pathway inhibitors\",\n      \"journal\": \"Frontiers in endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown combined with selective agonists and pathway inhibitors; single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"36967764\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"mPRα (PAQR7) activation in Schwann cell-like adipose stem cells (SCL-ASC) promotes cell migration, differentiation, morphology changes, and BDNF release. mPRα localization changed upon activation. Src and PI3K-Akt signaling pathways are required for mPRα activity in SCL-ASC. mPRα siRNA confirmed this isoform is responsible.\",\n      \"method\": \"siRNA knockdown of mPRα, selective mPR agonist Org OD 02-0, cell migration assays, BDNF ELISA, pathway inhibitors, immunofluorescence for localization\",\n      \"journal\": \"Molecular and cellular endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown, selective agonist, multiple functional readouts, subcellular localization; single lab\",\n      \"pmids\": [\"33930460\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"mPRα (PAQR7) activation in Schwann cell-like adipose stem cells (SCL-ASC) promotes neurite outgrowth in co-cultured neuronal cells (IMR-32 and SH-SY5Y) through SCL-ASC-dependent release of BDNF and IGF-2, while direct mPRα activation on neuronal cells promotes cell survival. mPRα siRNA in SCL-ASC abolished the neurite outgrowth effect.\",\n      \"method\": \"Conditioned medium experiments, co-culture, siRNA knockdown of mPRα in SCL-ASC, selective agonist Org OD 02-0, BDNF/IGF-2 measurements\",\n      \"journal\": \"Journal of molecular neuroscience : MN\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown, conditioned medium, co-culture, and direct agonist approaches; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"35974286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PAQR7 deficiency in KGN granulosa cells increased apoptosis, which was rescued by P4 supplementation. Paqr7 knockout female mice showed prolonged estrous cycles, reduced follicular growth, increased atresia follicles, decreased E2 and AMH, reduced litter sizes, and impaired spontaneous ovulation. The anti-apoptotic mechanism involves the BCL-2/BAX/CASPASE-3 signaling pathway.\",\n      \"method\": \"siPAQR7 knockdown in KGN cells, Paqr7 knockout mouse model, follicle counting, hormone measurements, apoptosis assays, western blot for BCL-2/BAX/CASPASE-3\",\n      \"journal\": \"Journal of ovarian research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse model plus cell-based siRNA knockdown, multiple reproductive phenotype readouts, pathway analysis; single lab\",\n      \"pmids\": [\"38317224\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"A Paqr7 structural homolog (Paqr7b) in half-smooth tongue sole fish ovary is required for progestin-induced oocyte maturation. Morpholino antisense knockdown of Paqr7b in oocytes blocked progestin-induced maturation. Paqr7b expression in oocytes and pituitary was regulated by gonadotropin in a dose- and stage-dependent manner.\",\n      \"method\": \"Morpholino antisense oligonucleotide microinjection in oocytes, in situ hybridization, immunohistochemistry, cDNA cloning and phylogenetic analysis\",\n      \"journal\": \"General and comparative endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — morpholino knockdown with direct functional readout (oocyte maturation); fish ortholog/paralog, single lab\",\n      \"pmids\": [\"27554928\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"2-Hydroxypentanoic acid (2-HPA) from marine algae Padina shows competitive binding to human mPRα (PAQR7) in a GQD-mPRα binding assay and inhibits fish oocyte maturation and ovulation in vivo. Both S- and R-stereoisomers showed equal activity. Structural analogues of 2-HPA lacked competitive binding, indicating structural specificity. 2-HPA acts as a novel mPRα antagonist.\",\n      \"method\": \"GQD-mPRα competitive binding assay, goldfish oocyte maturation assay in vitro, zebrafish ovulation assay in vivo\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — binding assay plus functional assay in fish model; novel finding but single lab, single paper\",\n      \"pmids\": [\"39922053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"PGLP (an alias for PAQR7) was identified as a PPARgamma1-target gene encoding a 38 kDa cytoplasmic membranous protein that is dramatically induced in mouse liver following PPARgamma1 overexpression (adenoviral approach) but not by fasting or choline deficiency-induced fatty liver. Full-length cDNA was cloned.\",\n      \"method\": \"Affymetrix microarray, adenoviral PPARgamma1 overexpression in PPARalpha-deficient mouse liver, cDNA cloning, northern blot\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — gene expression induction identified by microarray with validation; no mechanistic functional characterization of the PGLP/PAQR7 protein itself\",\n      \"pmids\": [\"15589683\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PAQR7 (mPRα) is a 7-transmembrane membrane progesterone receptor with an intracellular N-terminus and a zinc-containing ligand-binding pocket (homologous to AdipoRs) where progesterone binds via a critical H-bond to Q206; upon progesterone binding, it couples to inhibitory G proteins (Gi) to decrease cAMP, activate MAP kinase/ERK and Akt/PI3K pathways, downregulate RhoA/ROCK and Ca2+ channel activity, upregulate SERCA2/phospholamban function, and reduce myosin light chain phosphorylation, collectively inducing vascular smooth muscle relaxation; in reproductive cells it mediates anti-apoptotic signaling through BCL-2/BAX/CASPASE-3, in neural/Schwann cells it promotes survival, migration, and BDNF/IGF-2 release via Src and PI3K-Akt, and in granulosa cells it supports ovarian follicle development and oocyte maturation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PAQR7 (mPRα) is a membrane progesterone receptor that transduces rapid, non-genomic progesterone signaling through inhibitory G protein (Gi) coupling, with prominent roles in vascular smooth muscle relaxation, neural cell survival, and ovarian follicle development [#0, #5, #8]. In human vascular smooth muscle cells, progesterone acting through mPRα—but not the nuclear progesterone receptor—couples to Gi to lower cAMP, activate MAP kinase/ERK and Akt/PI3K signaling, and reduce myosin light chain phosphorylation, producing relaxation [#0]. This pathway lowers cytosolic Ca2+ by downregulating RhoA/ROCK activity [#1] and by upregulating SERCA2 expression and phospholamban phosphorylation to drive Ca2+ uptake into the sarcoplasmic reticulum [#2]. Ligand recognition occurs through a zinc-containing pocket modeled on the adiponectin receptors, in which a hydrogen bond between Q206 and the progesterone 20-carbonyl is essential for binding; mutation of Q206 or V146 abolishes progesterone binding, and the AdipoR agonist AdipoRon mimics progesterone signaling at the receptor [#3, #4]. Beyond the vasculature, mPRα mediates progesterone neuroprotection in dopaminergic cell models via PI3K-AKT and MAP kinase pathways [#5], drives Schwann cell-like adipose stem cell migration, differentiation, and BDNF/IGF-2 release through Src and PI3K-Akt signaling to support neurite outgrowth and neuronal survival [#6, #7], and protects granulosa cells from apoptosis via BCL-2/BAX/CASPASE-3 signaling, with Paqr7 knockout mice showing impaired follicular growth, ovulation, and fertility [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Before functional characterization, the question was whether PAQR7 (then PGLP) was a regulated gene of defined tissue context; it was placed downstream of PPARgamma1 as an inducible cytoplasmic membranous protein.\",\n      \"evidence\": \"Affymetrix microarray and adenoviral PPARgamma1 overexpression in mouse liver with cDNA cloning\",\n      \"pmids\": [\"15589683\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No mechanistic function assigned to the protein\", \"Link to progesterone signaling not yet established\", \"Single transcriptional induction observation\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"To test whether PAQR-family membrane progesterone receptors are functionally required for reproduction, a tongue sole homolog was knocked down, establishing a role in progestin-induced oocyte maturation.\",\n      \"evidence\": \"Morpholino knockdown in fish oocytes with in situ hybridization and gonadotropin regulation analysis\",\n      \"pmids\": [\"27554928\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Fish ortholog/paralog, not human PAQR7\", \"Downstream signaling pathway not delineated\", \"Receptor-ligand binding not directly shown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The central question of how progesterone produces rapid vascular effects was answered by showing mPRα couples to Gi to relax vascular smooth muscle independently of the nuclear receptor.\",\n      \"evidence\": \"Collagen gel and artery ring contraction assays, reciprocal mPRα vs nPR siRNA knockdown, pertussis toxin, and pathway inhibitors in human VSMCs\",\n      \"pmids\": [\"29428395\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct receptor-G protein interaction not structurally resolved\", \"In vivo vascular relevance not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Building on Gi coupling, the downstream effector arm was defined by showing mPRα lowers cytosolic Ca2+ through cAMP and MAPK/Akt downregulation and decreased RhoA/ROCK activity.\",\n      \"evidence\": \"Intracellular Ca2+ imaging, RhoA activity assay, siRNA knockdown, and pathway inhibitors in human umbilical artery VSMCs\",\n      \"pmids\": [\"31416049\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Connection between RhoA downregulation and Ca2+ handling not fully resolved\", \"Membrane proximal events between receptor and RhoA unmapped\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The Ca2+-lowering mechanism was mechanistically completed by identifying SERCA2 upregulation and phospholamban phosphorylation as the effectors driving SR Ca2+ uptake and relaxation.\",\n      \"evidence\": \"SERCA2 siRNA knockdown, SERCA inhibitor CPA, SR Ca2+ measurement, and immunoblotting for PLB phosphorylation\",\n      \"pmids\": [\"33427050\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking PI3K/Akt to PLB phosphorylation not defined\", \"SERCA2 transcriptional vs post-translational induction not separated\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To extend mPRα beyond vasculature, its activation in Schwann cell-like adipose stem cells was shown to promote migration, differentiation, and BDNF release via Src and PI3K-Akt.\",\n      \"evidence\": \"siRNA knockdown, selective agonist Org OD 02-0, migration assays, BDNF ELISA, and immunofluorescence localization\",\n      \"pmids\": [\"33930460\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of agonist-induced relocalization unknown\", \"Direct Src activation by the receptor not shown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The molecular basis of ligand recognition was addressed by homology modeling and mutagenesis, defining a zinc-containing pocket and an essential Q206 hydrogen bond to progesterone.\",\n      \"evidence\": \"AdipoR1-based homology model, site-directed mutagenesis (Q206R, V146S), [3H]-progesterone radioligand binding, and AdipoRon/D-e-MAPP pharmacology\",\n      \"pmids\": [\"35189329\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No experimental structure of PAQR7\", \"Single lab; model-based predictions\", \"Zinc stoichiometry and catalytic relevance not established\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Direct ligand binding was independently confirmed using a graphene quantum dot-conjugated receptor assay showing competitive progesterone binding.\",\n      \"evidence\": \"Fluorescence-based competitive binding with GQD-mPRα and progesterone-BSA-FITC\",\n      \"pmids\": [\"35007844\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method, single lab\", \"Binding affinity and kinetics not quantified\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The neural role was broadened by showing mPRα-activated SCL-ASCs promote neurite outgrowth in neurons via secreted BDNF and IGF-2, while direct neuronal mPRα activation promotes survival.\",\n      \"evidence\": \"Conditioned medium, co-culture, siRNA knockdown in SCL-ASC, selective agonist, and BDNF/IGF-2 measurement\",\n      \"pmids\": [\"35974286\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Paracrine vs direct contributions in vivo unquantified\", \"Signaling linking mPRα to BDNF/IGF-2 secretion not mapped\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether mPRα mediates progesterone neuroprotection was tested in a Parkinson's disease cell model, showing selective mPR agonism protects against neurotoxins via PI3K-AKT and MAP kinase.\",\n      \"evidence\": \"siRNA knockdown, selective agonist Org OD 02-0 vs R5020 vs muscimol, viability assays, and pathway inhibitors in SH-SY5Y cells\",\n      \"pmids\": [\"36967764\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vivo neuroprotection demonstrated\", \"Downstream survival effectors not identified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The reproductive requirement for PAQR7 in mammals was established, linking its anti-apoptotic BCL-2/BAX/CASPASE-3 signaling to follicle development and fertility.\",\n      \"evidence\": \"siPAQR7 in KGN granulosa cells with P4 rescue, Paqr7 knockout mice, follicle counts, hormone measurements, and apoptosis pathway western blots\",\n      \"pmids\": [\"38317224\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Coupling between receptor and BCL-2/BAX regulation not delineated\", \"Single lab; granulosa-specific vs systemic contributions not separated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Pharmacological tractability of the ligand pocket was probed by identifying 2-HPA as a competitive natural antagonist with structural specificity.\",\n      \"evidence\": \"GQD-mPRα competitive binding assay, goldfish oocyte maturation, and zebrafish ovulation assays\",\n      \"pmids\": [\"39922053\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single lab, single paper\", \"Antagonism validated in fish, not human cells\", \"No structural confirmation of binding site engagement\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How mPRα physically engages Gi at the membrane and how a single receptor selects between vascular relaxation, neuroprotective, and anti-apoptotic outputs in different cell types remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No experimental receptor structure or receptor-G protein complex\", \"Cell-type-specific effector selection unexplained\", \"In vivo vascular and neural functions largely untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [8, 9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}