Affinage

PCSK7

Proprotein convertase subtilisin/kexin type 7 · UniProt Q16549

Length
785 aa
Mass
86.2 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCSK7 encodes PC7, a type-I membrane-bound subtilisin/kexin-like serine proprotein convertase that is synthesized as a glycosylated zymogen, autoactivated by removal of its RAKR-ending prosegment principally in the ER, and traffics to the cell surface and endosomes through both a conventional Golgi-dependent route and an unconventional brefeldin A- and COPII-independent route specified by its transmembrane domain (PMID:8622945, PMID:9242622, PMID:21075846). Its own prosegment is a potent competitive inhibitor whose C-terminal helical decapeptide retains nanomolar inhibitory activity dependent on a P1 Arg (PMID:10567353, PMID:10715106). PC7 cleaves a broad set of precursors at basic motifs to control diverse processes: it processes proVEGF-C to drive angiogenesis and tumor growth (PMID:12782675), preprohepcidin to its active hormone (PMID:18664504), the S1 site of pro-BMP4 (PMID:19651771), and proBDNF to mature BDNF, with PC7 knockout mice showing reduced hippocampal/amygdalar BDNF and impaired memory rescuable by a TrkB agonist (PMID:24101515). Substrate selection is conformation-dependent, as PC7 fails to cleave integrin α-subunit precursors despite appropriate sequences (PMID:10657249), and several substrates are shared redundantly with Furin, PACE4 and PC5 (proalbumin, E-cadherin, gp160) (PMID:10050053, PMID:26416966, PMID:9094426). Compartmentalized activity is governed by cytosolic-tail motifs: a clathrin/AP-2 internalization motif and the EXEXXXL motif direct endosomal recycling and shedding of substrates such as transferrin receptor-1 and CASC4, while a PLC motif controls TGN recycling required for proActivin-A processing (PMID:22294700, PMID:31915245, PMID:32820145, PMID:29466742). PC7 also acts non-enzymatically in hepatic lipid metabolism, binding apoB100 in the ER to promote its secretion and chaperoning apoA-V to lysosomal degradation, such that Pcsk7 loss reduces hepatic lipid accumulation and improves recovery from NAFLD (PMID:37967646, PMID:31945259). Additional roles include a second quality-control checkpoint in MHC class I antigen presentation (PMID:20164418) and indirect activation of pro-EGF processing that potentiates EGFR/ERK signaling (PMID:21209099).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 High

    Established PC7 as a distinct, most-divergent mammalian proprotein convertase, defining the molecular substrate for all subsequent functional study.

    Evidence cDNA cloning, phylogenetics, Northern blot and chromosomal mapping

    PMID:8622945

    Open questions at the time
    • No enzymatic activity or substrate demonstrated at this stage
    • Subcellular trafficking unknown
  2. 1997 High

    Defined PC7 as a Ca2+-dependent serine proteinase activated in the ER with furin-like but distinct substrate preferences, answering whether it is catalytically active and on what motifs.

    Evidence Recombinant overexpression with fluorogenic and synthetic peptide cleavage assays

    PMID:9094426 PMID:9242622

    Open questions at the time
    • Physiological substrates not yet identified
    • gp160 cleavage shown only in overexpression contexts
  3. 2000 High

    Characterized the PC7 prosegment as a folded, nanomolar competitive autoinhibitor, defining the enzyme's intrinsic regulatory mechanism and a tool for inhibition.

    Evidence In vitro inhibition assays, mutagenesis, NMR structure of the prosegment peptide

    PMID:10567353 PMID:10715106

    Open questions at the time
    • Endogenous timing/location of prosegment release in vivo not resolved
  4. 2003 High

    Demonstrated bona fide physiological precursor processing by PC7, showing proVEGF-C cleavage is required for angiogenesis and tumor growth and resolving its in vivo relevance.

    Evidence Cell-based processing in furin-deficient cells, in vitro digestion, cleavage-site mutagenesis, nude-mouse tumor model

    PMID:12782675

    Open questions at the time
    • Redundancy with furin/PC5 leaves PC7-specific contribution in vivo unquantified
  5. 2009 High

    Extended the PC7 substrate repertoire to hepcidin and pro-BMP4, showing both redundant and site-selective processing among convertases.

    Evidence Cell transfection, mutagenesis, in vitro peptide digestion, selective α1-PDX variants, Xenopus knockdown

    PMID:18664504 PMID:19651771

    Open questions at the time
    • Relative contribution of PC7 vs furin/PC5 in physiological tissue not established
  6. 2010 High

    Resolved PC7 trafficking, showing ER activation followed by routing to surface/endosomes via conventional and unconventional TMD-determined pathways, and uncovered non-redundant roles in MHC I antigen presentation.

    Evidence Subcellular fractionation, EM, BFA treatment, TMCT chimeras, siRNA knockdown with MHC I surface/MS readouts

    PMID:20164418 PMID:21075846

    Open questions at the time
    • Molecular determinants of unconventional secretion beyond TMD unknown
    • MHC I peptide-trimming protease activity vs adaptor role not fully separated
  7. 2011 High

    Showed PC7 activates pro-EGF processing indirectly via a downstream protease, linking it to EGFR/ERK signaling rather than direct cleavage.

    Evidence Overexpression/knockdown, cleavage-site mutagenesis, protease inhibitor panel, EGFR/ERK phosphorylation, surface biotinylation

    PMID:21209099

    Open questions at the time
    • Identity of the latent protease activated by PC7 not determined
  8. 2013 High

    Established an in vivo neurological function: PC7 maturation of proBDNF supports hippocampal BDNF and memory, with developmental roles confirmed in zebrafish.

    Evidence Cell processing assays, PC7 KO mouse behavior with TrkB agonist rescue, zebrafish morpholino knockdown with TGFβ1a epistasis

    PMID:24101515 PMID:24178295

    Open questions at the time
    • Cell-type and circuit basis of memory phenotype not dissected
    • Direct vs indirect TGFβ1a processing in zebrafish not fully separated
  9. 2018 High

    Defined cytosolic-tail motifs (clathrin internalization, PLC, EXEXXXL/AP-2) that compartmentalize PC7 activity in endosomes vs TGN, controlling substrate-specific processing and shedding.

    Evidence Clathrin inhibition, coated-vesicle isolation, tail mutagenesis, compartment biosensors, AP-2 interaction, NMR of tail peptides, TfR1/CASC4/proActivin-A/Notch1 assays

    PMID:22294700 PMID:29466742 PMID:31915245 PMID:32820145

    Open questions at the time
    • How compartment choice is regulated dynamically in physiology unclear
    • Functional consequences of TfR1/CASC4 shedding in vivo not established
  10. 2023 High

    Revealed non-enzymatic roles of PC7 in hepatic lipid metabolism—apoB100 binding/secretion and apoA-V lysosomal degradation—implicating PCSK7 in NAFLD.

    Evidence Co-IP binding, ER-retained mutants, lysosomal inhibitors, phosphorylation assays, Pcsk7-/- mice and GalNAc-ASO knockdown with UPR/autophagy/β-oxidation readouts

    PMID:31945259 PMID:37967646

    Open questions at the time
    • Structural basis of apoB100/apoA-V binding undefined
    • Relationship between catalytic and chaperone functions in liver not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PC7's catalytic, chaperone, and trafficking activities are coordinated, and how the R504H/regulatory variants modulate human disease, remains unresolved.
  • No causative Mendelian disease link established
  • R504H reported to alter apoA-V handling but not classical substrate processing, leaving its physiological role ambiguous

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0005764 lysosome 2 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 1 R-HSA-168256 Immune System 1
Partners
AP-2APOA-VAPOB100

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 PCSK7 (PC7) encodes a type I membrane-bound glycoprotein with a 36-aa signal peptide, 104-aa prosegment ending in RAKR, and a 747-aa mature serine proteinase; phylogenetic analysis places it as the most divergent mammalian convertase and closest to yeast kexin/krp convertases. cDNA cloning, sequence analysis, Northern blot, in situ hybridization, chromosomal linkage mapping Proceedings of the National Academy of Sciences of the United States of America High 8622945
1997 Rat PC7 is synthesized as a 101-kDa glycosylated zymogen, processed to an 89-kDa mature form in the endoplasmic reticulum; enzymatic assays show pH optimum, Ca2+ dependence, and cleavage specificity largely similar to furin but with some kexin-like substrate preferences; PC7 correctly processes peptides containing the pro-PTH and pro-PC4 processing sites but not a pro-EGF site. Vaccinia-virus recombinant overexpression in BSC40 cells, fluorogenic peptide substrate assays, synthetic peptide cleavage, Western blot The Journal of biological chemistry High 9242622
1997 PC7 cleaves HIV-1 gp160 into gp120/gp41 in a cell-type-specific manner (active in BSC40 and T4 lymphocyte contexts) and in vitro on a synthetic peptide spanning the cleavage site; both furin and PC7 are upregulated 5–10-fold in HIV-replication-promoting activated T4 lymphocytes. Co-expression in BSC40 and AtT20 cells, in vitro gp160 cleavage assay, RT-PCR FEBS letters Medium 9094426
1999 Purified recombinant prosegments of furin and PC7 are potent, moderately selective inhibitors of their parent enzymes in vitro (inhibiting fluorogenic peptide cleavage and HIV gp160 processing); short C-terminal decapeptides of the prosegments retain inhibitory activity with the P1 Arg being essential; expressed ex vivo via vaccinia virus, the prosegments inhibit processing of NGF and BDNF in trans. In vitro fluorogenic peptide assay, recombinant prosegment purification, vaccinia virus ex vivo expression, Western blot The Journal of biological chemistry High 10567353
1999 PC7 overexpression increases APPα secretion and reduces Aβ40/42 levels in HEK293 cells; this effect is blocked by α1-PDX (a proprotein convertase inhibitor), indicating PC7 participates in the constitutive α-secretase pathway for APP processing. Transient transfection in HEK293 cells, ELISA/immunoassay for APPα and Aβ40/42, α1-PDX inhibitor Journal of neurochemistry Medium 10537065
1999 Furin and PC7 mRNAs and proteins co-localize with NGF in Schwann cells, macrophages, and perivascular smooth muscle cells of injured sciatic nerve, and both convertases are upregulated after nerve lesion, suggesting a role in pro-NGF processing. Northern blot, immunocytochemistry, in situ hybridization on nerve explants and in vivo injury model The Journal of comparative neurology Medium 9888313
2000 PC7 does not process integrin α-subunit precursors (pro-α5, α6, αv) either in vitro or ex vivo in LoVo cells, despite similar cleavage-site sequences to known PC7 substrates, indicating that substrate conformation determines PC7 accessibility. In vitro cleavage assay with recombinant PC7, LoVo cell co-expression (ex vivo), Western blot The Biochemical journal Medium 10657249
2000 A 24-residue C-terminal peptide of the PC7 prosegment (residues 81p–104p) inhibits PC7 with Ki = 7 nM and adopts a helical conformation in solution; the folded structure is proposed to underlie its potency as a competitive inhibitor. Enzyme inhibition assay, NMR structure determination with NOE restraints Biochemistry High 10715106
2003 Furin, PC5, and PC7 cleave proVEGF-C within the dibasic motif HSIIRR227↓SL to generate mature VEGF-C; this processing is required for VEGF-C-induced angiogenesis, lymphangiogenesis, and tumor growth in nude mice. Co-transfection in furin-deficient LoVo cells, in vitro fluorogenic peptide digestion, subcutaneous CHO cell injection into nude mice, cleavage-site mutagenesis The Journal of clinical investigation High 12782675
2008 PC7 (along with Furin, PACE4, and PC5) cleaves the preprohepcidin convertase site RRRRR59↓DT to generate active hepcidin; cleavage was demonstrated in Huh-7 cells and by in vitro synthetic peptide digestion; the RRRRR59→SSSSS mutant is not processed and is biologically inactive. Cell transfection in Huh-7 and LoVo cells, site-directed mutagenesis, in vitro peptide digestion, furin inhibitors (α1-PDX, ppFurin) Gut Medium 18664504
2009 PC7 (or a convertase with similar substrate specificity) selectively cleaves the S1 site of pro-BMP4 in Xenopus embryos, whereas furin and PC6 redundantly cleave both S1 and S2 sites; this was established using engineered α1-PDX variants that differentially target PC7 vs. furin/PC6. Antisense-mediated knockdown in Xenopus oocytes and embryos, engineered furin/PC6/PC7-selective inhibitor (α1-PDX variant), pro-BMP4 processing assays The Journal of biological chemistry High 19651771
2010 PC7 zymogen activation occurs primarily in the ER; mature PC7 is partially sulfated and traffics to the cell surface via both a conventional Golgi-dependent pathway and an unconventional brefeldin A- and COPII-independent pathway; cysteines 699 and 704 in the cytosolic tail are palmitoylated but palmitoylation does not control pathway choice; the transmembrane domain of PC7 determines routing to the unconventional pathway, as shown by chimeric Furin-PC7 TMCT swap experiments. Biochemical subcellular fractionation, electron microscopy, brefeldin A treatment, palmitoylation assay, TMCT chimera construction and trafficking analysis, sulfation assay The Journal of biological chemistry High 21075846
2010 PC7, but not furin, provides a second quality control checkpoint in antigen presentation: PC7-silenced cells with a malfunctioning peptide-loading complex show substantially reduced MHC I surface levels, enhanced MHC I degradation in lysosomes, delayed surface accumulation, and an altered MHC I-presented peptide profile; PC7 is required for liberation of certain MHC I epitopes from exogenously applied peptide precursors. PC7 siRNA knockdown, MHC I surface staining, mass spectrometry of presented peptides, exogenous peptide loading assays Journal of immunology High 20164418
2011 PC7 induces processing of membrane-bound pro-EGF into a ~115-kDa transmembrane form (EGF-115) at an VHPR290↓A motif; site-directed mutagenesis shows Arg290 is not critical, indicating the processing is indirect (via activation of a latent serine and/or cysteine protease by PC7); EGF-115 is more abundant at the cell surface than pro-EGF and is associated with stronger EGFR activation and higher pERK1/2 levels. PC7 overexpression/knockdown, site-directed mutagenesis of cleavage site, protease inhibitor panel, EGFR/ERK phosphorylation assays, cell surface biotinylation The Journal of biological chemistry High 21209099
2012 PC7 internalization from the plasma membrane is mediated by clathrin-coated vesicles; a novel motif between Ala713 and Cys726 in the cytoplasmic tail, containing Pro, Leu, and Cys as essential residues, is necessary and sufficient for PC7 internalization but not for TGN localization. Clathrin inhibition (hypertonic conditions, Pitstop 2), isolation of clathrin-coated vesicles, cytoplasmic tail deletion and alanine-scanning mutagenesis, antibody uptake and surface biotinylation experiments The Journal of biological chemistry High 22294700
2013 PC7 processes proBDNF into mature BDNF in COS-1 cells and in primary mouse hepatocytes; mature BDNF levels are reduced in hippocampus and amygdala of PC7 KO mice but not PC1/3 KO mice; PC7 KO mice have severely impaired episodic and emotional memory, which is rescued by the TrkB agonist 7,8-dihydroxyflavone, establishing an in vivo role for PC7 in proBDNF processing and cognitive function. COS-1 cell co-transfection, primary hepatocyte analysis, PC7 KO mouse model, BDNF ELISA/Western blot, behavioral tests, TrkB agonist rescue Proceedings of the National Academy of Sciences of the United States of America High 24101515
2013 PCSK7 is essential for zebrafish development; pcsk7 morphant larvae have defects in brain, eye, and otic vesicle, leading to mortality by 7 dpf; PCSK7 contributes to mRNA expression and proteolytic cleavage of TGFβ1a, and tgfβ1a morphants phenocopy pcsk7 morphants. Morpholino knockdown in zebrafish larvae, homology structural modeling, genome-wide gene expression analysis, TGFβ1a cleavage assay The Journal of biological chemistry High 24178295
2015 PC7, Furin, and Pace4 regulate E-cadherin processing during morula compaction and blastocyst formation; loss of these convertases impairs cell-cell adhesion and inner cell mass formation; spatial PC activity profiles mapped by live imaging of transgenic reporter substrate show PC7 is active in partially non-overlapping compartments from Furin. PC mutant mouse embryo analysis, live imaging of transgenic fluorescent PC reporter, differential inhibitor profiling The Journal of cell biology High 26416966
2018 Compartment-specific biosensors reveal that endogenous PC7 is active in distinct vesicles from Furin; a PLC motif in the cytosolic tail of PC7 is dispensable for endosomal activity but required for TGN recycling and for rescuing proActivin-A cleavage in Furin-depleted cells; PC7 complements Furin in Notch1 cleavage independently of PLC-mediated TGN access. Compartment-targeted biosensors, PC7 PLC-motif mutagenesis, Furin depletion in B16F1 cells, Notch1 and proActivin-A processing assays Cell reports High 29466742
2020 PC7 sheds human transferrin receptor 1 (hTfR1) into soluble sTfR1 in endosomes; the EXEXXXL725 motif in the PC7 cytosolic tail is critical for endosomal trafficking and shedding activity; adaptor protein 2 (AP-2) recognizes this motif; Leu-725 enhances PC7 localization to early endosomes; NMR of 14-mer CT peptides reveals that Glu-719, Glu-721, and Leu-725 are on the same face of the helix. CT deletion and point mutagenesis, hTfR1 shedding assay, immunocytochemistry, AP-2 interaction assay, NMR of CT peptides The Journal of biological chemistry High 31915245
2020 PC7 and Furin shed Cancer Susceptibility Candidate 4 (CASC4) at the KR66↓NS site in acidic endosomes and/or the trans-Golgi network; CASC4 shedding disrupts its anti-migratory role, and the N-terminal PC7/Furin-generated membrane-bound fragment promotes podosome-like structures, enhancing cellular migration and invasion in MDA-MB-231 cells. Quantitative N-glycoproteomic screen, CASC4 mutagenesis at cleavage site, siRNA knockdown of CASC4, stable CASC4 overexpression, migration/invasion assays, paxillin focal adhesion imaging Cell death & disease High 32820145
2020 Wild-type PC7 and its ER-retained forms bind apolipoprotein A-V (apoA-V) and enhance its degradation in acidic lysosomes via a nonenzymatic mechanism; PC7-induced apoA-V degradation is inhibited by bafilomycin A1, chloroquine, and NH4Cl, implicating ER-lysosomal communication; the natural R504H variant enhances Ser505 phosphorylation by Fam20C; the phosphomimetic S505E mutant shows reduced apoA-V degradation; Pcsk7-/- mice on high-fat diet have elevated plasma apoA-V and increased adipocyte LpL activity. HuH7 cell overexpression, co-immunoprecipitation, lysosomal inhibitor treatments, phosphorylation assay, Pcsk7-/- mouse model, adipocyte LpL activity assay The FEBS journal High 31945259
2023 Membrane-bound PCSK7 binds apoB100 in the ER and enhances its secretion independent of proteolytic activity; loss of PCSK7 leads to apoB100 degradation via ubiquitination and the proteasome, triggering unfolded protein response, autophagy, and β-oxidation, ultimately reducing hepatic lipid accumulation; Pcsk7-/- mice recover more effectively from diet-induced NAFLD; GalNAc-ASO-mediated hepatic Pcsk7 silencing recapitulates these phenotypes. Hepatic cell line experiments, co-IP for PC7-apoB100 binding, Pcsk7-/- mouse NAFLD model, GalNAc-ASO knockdown, proteasome inhibition, UPR/autophagy/β-oxidation assays Metabolism: clinical and experimental High 37967646
2014 PC7 siRNA upregulates HIF-1α protein in normoxic squamous carcinoma cells to levels similar to hypoxia mimetics; this is a post-transcriptional effect occurring at the level of HIF-1α translation (cycloheximide chase); the induction requires IGF-1R signaling and leads to VEGF-A upregulation. siRNA knockdown of PC7 and furin, Western blot, RT-PCR, cycloheximide chase, IGF-1R signaling inhibitor treatment Molecular carcinogenesis Medium 24436242
2014 PC7 and its R504H mutant exhibit similar processing of transferrin receptor-1, proSortilin, and apolipoprotein-F; plasma lipid profiles and insulin/glucose levels are unchanged in PC7 KO mice, indicating that the R504H mutation does not alter PC7 proteolytic activity toward these substrates. Cell-based processing assays for TfR1, proSortilin, apoF; plasma lipid and metabolic analysis in PC7 KO mice FEBS open bio Medium 25349778
2022 miR-125a-5p, miR-143-3p, and miR-409-3p directly interact with the 3'-UTR of human PCSK7 mRNA and downregulate PC7 expression; overexpression of miR-125a-5p in Huh7 cells inhibits PC7 protein levels and reduces PC7-mediated cleavage of hTfR1. Dual-luciferase assay, Western blot, qPCR, transfection of miRNA overexpression vectors, hTfR1 cleavage assay Metabolites Medium 35888711
1999 PC8 (PCSK7) endogenously participates in proalbumin processing in HepG2 hepatoma cells alongside PACE4 and furin; antisense-mediated knockdown of PC8 in HepG2 cells results in approximately 30% inhibition of proalbumin-to-albumin processing, demonstrating functional redundancy among these convertases in hepatocytes. Northern blot of HepG2 expression, co-expression processing assay, stable antisense RNA knockdown, albumin processing Western blot Journal of biochemistry Medium 10050053

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Role of lysophosphatidylcholine (LPC) in atherosclerosis. Current medicinal chemistry 281 18220755
1996 cDNA structure, tissue distribution, and chromosomal localization of rat PC7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinases. Proceedings of the National Academy of Sciences of the United States of America 221 8622945
2003 The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis. The Journal of clinical investigation 175 12782675
1999 Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. Clinical and experimental immunology 154 10337026
2009 G2A and LPC: regulatory functions in immunity. Prostaglandins & other lipid mediators 124 19383550
1999 The prosegments of furin and PC7 as potent inhibitors of proprotein convertases. In vitro and ex vivo assessment of their efficacy and selectivity. The Journal of biological chemistry 109 10567353
1996 A new member of the proprotein convertase gene family (LPC) is located at a chromosome translocation breakpoint in lymphomas. Cancer research 96 8564950
2000 Endoproteolytic processing of integrin pro-alpha subunits involves the redundant function of furin and proprotein convertase (PC) 5A, but not paired basic amino acid converting enzyme (PACE) 4, PC5B or PC7. The Biochemical journal 93 10657249
1996 PC8 [corrected], a new member of the convertase family. The Biochemical journal 83 8615762
2023 Regulatory T cells alleviate myelin loss and cognitive dysfunction by regulating neuroinflammation and microglial pyroptosis via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination. Journal of neuroinflammation 79 36803990
1997 In vitro characterization of the novel proprotein convertase PC7. The Journal of biological chemistry 74 9242622
2012 Triacylglycerol synthesis by PDAT1 in the absence of DGAT1 activity is dependent on re-acylation of LPC by LPCAT2. BMC plant biology 71 22233193
2013 Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. Proceedings of the National Academy of Sciences of the United States of America 67 24101515
2009 Site-specific cleavage of BMP4 by furin, PC6, and PC7. The Journal of biological chemistry 60 19651771
2010 Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels. Human molecular genetics 58 21149283
2009 A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice. American journal of physiology. Endocrinology and metabolism 51 19773578
2019 PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients. Journal of lipid research 49 30918065
2010 The proprotein convertase PC7: unique zymogen activation and trafficking pathways. The Journal of biological chemistry 49 21075846
2006 Short polybasic peptide sequences are potent inhibitors of PC5/6 and PC7: Use of positional scanning-synthetic peptide combinatorial libraries as a tool for the optimization of inhibitory sequences. Molecular pharmacology 47 17012622
1984 Effects of palmitoyl carnitine and LPC on cardiac sarcolemmal Na+-K+-ATPase. The American journal of physiology 47 6093598
1997 Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160. FEBS letters 46 9094426
2022 Transforming growth factor-β1 protects against LPC-induced cognitive deficit by attenuating pyroptosis of microglia via NF-κB/ERK1/2 pathways. Journal of neuroinflammation 45 35902863
2014 Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis. Human molecular genetics 45 24556216
1999 Nerve growth factor and proprotein convertases furin and PC7 in transected sciatic nerves and in nerve segments cultured in conditioned media: their presence in Schwann cells, macrophages, and smooth muscle cells. The Journal of comparative neurology 42 9888313
2020 Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model. Journal of neuroinflammation 40 33158440
2008 Simultaneous stimulation of spinal NK1 and NMDA receptors produces LPC which undergoes ATX-mediated conversion to LPA, an initiator of neuropathic pain. Journal of neurochemistry 40 19014389
2010 Post-endoplasmic reticulum rescue of unstable MHC class I requires proprotein convertase PC7. Journal of immunology (Baltimore, Md. : 1950) 37 20164418
1999 Proprotein convertase activity contributes to the processing of the Alzheimer's beta-amyloid precursor protein in human cells: evidence for a role of the prohormone convertase PC7 in the constitutive alpha-secretase pathway. Journal of neurochemistry 36 10537065
2014 PCSK7 genotype modifies effect of a weight-loss diet on 2-year changes of insulin resistance: the POUNDS LOST trial. Diabetes care 35 25504030
2017 TRPM2 contributes to LPC-induced intracellular Ca2+ influx and microglial activation. Biochemical and biophysical research communications 31 28223219
2021 LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4. Frontiers in neuroscience 30 34276296
2021 Procaspase-1 patrolled to the nucleus of proatherogenic lipid LPC-activated human aortic endothelial cells induces ROS promoter CYP1B1 and strong inflammation. Redox biology 30 34598017
2020 Effect of oral consumption of capsules containing Lactobacillus paracasei LPC-S01 on the vaginal microbiota of healthy adult women: a randomized, placebo-controlled, double-blind crossover study. FEMS microbiology ecology 29 32383767
2019 Antioxidant activity changes of exopolysaccharides with different carbon sources from Lactobacillus plantarum LPC-1 and its metabolomic analysis. World journal of microbiology & biotechnology 29 31011829
2017 Safety evaluation of HOWARU® Restore (Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium animalis subsp. lactis Bl-04 and B. lactis Bi-07) for antibiotic resistance, genomic risk factors, and acute toxicity. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 29 29080807
1999 Subtilisin-like proprotein convertases, PACE4 and PC8, as well as furin, are endogenous proalbumin convertases in HepG2 cells. Journal of biochemistry 29 10050053
2015 TSG attenuates LPC-induced endothelial cells inflammatory damage through notch signaling inhibition. IUBMB life 27 26662286
2008 Regulation of prohepcidin processing and activity by the subtilisin-like proprotein convertases Furin, PC5, PACE4 and PC7. Gut 27 18664504
2001 Selective expression of the proprotein convertases furin, pc5, and pc7 in proliferating vascular smooth muscle cells of the rat aorta in vitro. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 27 11181735
1994 A novel member, PC7, of the mammalian kexin-like protease family: homology to PACE4A, its brain-specific expression and identification of isoforms. Biochemical and biophysical research communications 27 8060327
1998 The pro-protein convertase PC1 is induced in the transected sciatic nerve and is present in cultured Schwann cells: comparison with PC5, furin and PC7, implication in pro-BDNF processing. Brain research. Molecular brain research 26 9729404
2021 Astragaloside IV Inhibits Bleomycin-Induced Ferroptosis in Human Umbilical Vein Endothelial Cells by Mediating LPC. Oxidative medicine and cellular longevity 25 34760046
2015 The vaginal isolate Lactobacillus paracasei LPC-S01 (DSM 26760) is suitable for oral administration. Frontiers in microbiology 25 26441886
2018 The atherogenic actions of LPC on vascular smooth muscle cells and its LPA receptor mediated mechanism. Biochemical and biophysical research communications 24 30064908
2017 EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination. Journal of neuroinflammation 24 29246262
2019 VEGF- and PDGF-dependent proliferation of oligodendrocyte progenitor cells in the medulla oblongata after LPC-induced focal demyelination. Journal of neuroimmunology 22 31075641
2011 Proprotein convertase PC7 enhances the activation of the EGF receptor pathway through processing of the EGF precursor. The Journal of biological chemistry 21 21209099
2000 Inhibitory activity and structural characterization of a C-terminal peptide fragment derived from the prosegment of the proprotein convertase PC7. Biochemistry 21 10715106
1995 Magnesium antagonizes the actions of lysophosphatidyl choline (LPC) in myocardial cells: a possible mechanism for its antiarrhythmic effects. Anesthesia and analgesia 20 7762833
2018 Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution of Bioactive Furin and PC7. Cell reports 19 29466742
2015 PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation. The Journal of cell biology 19 26416966
2012 Internalization of proprotein convertase PC7 from plasma membrane is mediated by a novel motif. The Journal of biological chemistry 19 22294700
2025 ACSL1 Aggravates Thromboinflammation by LPC/LPA Metabolic Axis in Hyperlipidemia Associated Myocardial Ischemia-Reperfusion Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39853712
2020 Proprotein convertase 7 (PCSK7) reduces apoA-V levels. The FEBS journal 18 31945259
2009 Intracellular Ca(2+)- and PKC-dependent upregulation of T-type Ca(2+) channels in LPC-stimulated cardiomyocytes. Journal of molecular and cellular cardiology 18 19744490
2005 Laser pressure catapulting (LPC): optimization LPC-system and genotyping of colorectal carcinomas. Journal of cellular physiology 18 15316933
2023 PCSK7: A novel regulator of apolipoprotein B and a potential target against non-alcoholic fatty liver disease. Metabolism: clinical and experimental 17 37967646
2013 Assessment of the influence of amylose-LPC complexation on the extent of wheat starch digestibility by size-exclusion chromatography. Food chemistry 17 23993621
2006 Lysophosphatidylcholine (LPC) attenuates macrophage-mediated oxidation of LDL. Biochemical and biophysical research communications 17 16650824
2020 Shedding of cancer susceptibility candidate 4 by the convertases PC7/furin unravels a novel secretory protein implicated in cancer progression. Cell death & disease 16 32820145
2018 CXCR6 protects from inflammation and fibrosis in NEMOLPC-KO mice. Biochimica et biophysica acta. Molecular basis of disease 16 30476545
2013 Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a). The Journal of biological chemistry 16 24178295
2018 DFMG attenuates the activation of macrophages induced by co‑culture with LPC‑injured HUVE‑12 cells via the TLR4/MyD88/NF‑κB signaling pathway. International journal of molecular medicine 15 29484368
2024 Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation. Arteriosclerosis, thrombosis, and vascular biology 14 38299357
2022 Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest. Annals of neurology 14 34979595
2020 Longitudinal Intravital Microscopy Reveals Axon Degeneration Concomitant With Inflammatory Cell Infiltration in an LPC Model of Demyelination. Frontiers in cellular neuroscience 14 32655371
2015 Sulforaphane protected the injury of human vascular endothelial cell induced by LPC through up-regulating endogenous antioxidants and phase II enzymes. Food & function 14 26008201
2013 The influence of amylose-LPC complex formation on the susceptibility of wheat starch to amylase. Carbohydrate polymers 14 23911468
2023 Butyrate inhibits LPC-induced endothelial dysfunction by regulating nNOS-produced NO and ROS production. Nitric oxide : biology and chemistry 13 37308032
2004 Characterization of pC7 from Lactobacillus paraplantarum C7 derived from Kimchi and development of lactic acid bacteria--Escherichia coli shuttle vector. Plasmid 13 15336486
1999 Occurrence of an HIV-1 gp160 endoproteolytic activity in low-density vesicles and evidence for a distinct density distribution from endogenously expressed furin and PC7/LPC convertases. FEBS letters 13 10452538
1988 Immunoglobulin production stimulating and inhibiting factors derived from human lung adenocarcinoma PC-8 cells : Ig production stimulating factor in PC-8 cells. Cytotechnology 13 22359164
2022 Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development. Cell death & disease 12 36273194
2014 Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells. Molecular carcinogenesis 12 24436242
2024 Quercetin Mitigates Lysophosphatidylcholine (LPC)-Induced Neutrophil Extracellular Traps (NETs) Formation through Inhibiting the P2X7R/P38MAPK/NOX2 Pathway. International journal of molecular sciences 11 39273358
2021 The rs508487, rs236911, and rs236918 Genetic Variants of the Proprotein Convertase Subtilisin-Kexin Type 7 (PCSK7) Gene Are Associated with Acute Coronary Syndrome and with Plasma Concentrations of HDL-Cholesterol and Triglycerides. Cells 11 34207761
2018 A new cytotoxic 12-membered macrolactone from the endophytic fungus Exserohilum rostratum LPC-001. Journal of Asian natural products research 10 30595053
2014 Metallothionein-III increases ADAM10 activity in association with furin, PC7, and PKCα during non-amyloidogenic processing. FEBS letters 10 24859040
2014 Is there a link between proprotein convertase PC7 activity and human lipid homeostasis? FEBS open bio 10 25349778
1979 Studies with murine LPC-1 plasmacytoma using [6-14C]arginine. Cell and tissue kinetics 10 84712
2019 Agonism activities of lyso-phosphatidylcholines (LPC) Ligands binding to peroxisome proliferator-activated receptor gamma (PPARγ). Journal of biomolecular structure & dynamics 9 31025599
2000 Structure of HAP1-PC7 bound to DNA: implications for DNA recognition and allosteric effects of DNA-binding on transcriptional activation. Nucleic acids research 9 11024163
2021 Variants in PCSK7, PNPLA3 and TM6SF2 are risk factors for the development of cirrhosis in hereditary haemochromatosis. Alimentary pharmacology & therapeutics 8 33565643
2020 The motif EXEXXXL in the cytosolic tail of the secretory human proprotein convertase PC7 regulates its trafficking and cleavage activity. The Journal of biological chemistry 8 31915245
2006 LPC cepstral distortion measure for protein sequence comparison. IEEE transactions on nanobioscience 8 16805103
2006 Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro. Acta pharmacologica Sinica 8 17007739
1979 Temporary disappearance ("eclipse") of LPC-1 plasmacytoma M component synthesis following tumor cell transfer. Cancer research 8 445451
2022 Post-Transcriptional Effects of miRNAs on PCSK7 Expression and Function: miR-125a-5p, miR-143-3p, and miR-409-3p as Negative Regulators. Metabolites 7 35888711
2018 A liposome preparation based on β-CD-LPC molecule and its application as drug-delivery system. Nanomedicine (London, England) 7 30247090
2020 How types of prior knowledge and task properties impact the category-based induction: diverging evidence from the P2, N400, and LPC effects. Biological psychology 6 32890634
1987 Detection of residual murine LPC-1 myeloma cells from bone marrow cell mixture after purging by 4-hydroperoxycyclophosphamide. Experimental hematology 6 3297761
2025 The Biology and Clinical Implications of PCSK7. Endocrine reviews 5 39661471
2021 Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication. Journal of atherosclerosis and thrombosis 5 34565765
2018 The N1-N2-LPC Pattern in Processing Advertising Pictorial Metaphors: An ERP Study. Frontiers in psychology 5 30618984
1998 Senescent WI-38 fibroblasts overexpress LPC-1, a putative transmembrane shock protein. Experimental cell research 5 9597003
1998 Gene organization and alternative splicing of human prohormone convertase PC8. The Biochemical journal 5 9820811
1991 Nitroarginine does not inhibit lysophosphatidylcholine (LPC)-induced vascular relaxation and accumulation of cyclic GMP. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 5 1848940
2022 Design, synthesis, and characterization of novel fluorogenic substrates of the proprotein convertases furin, PC1/3, PC2, PC5/6, and PC7. Analytical biochemistry 4 35964735
1998 Molecular cloning and nucleotide sequence of 3'-terminal region of classical swine fever virus LPC vaccine strain. Virus genes 4 9926397
2025 Enhanced Microglial Engulfment of Dopaminergic Synapses Induces Parkinson's Disease-Related Executive Dysfunction in an Acute LPC Infusion Targeting the mPFC. Aging cell 3 39954245

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