Affinage

PCSK7

Proprotein convertase subtilisin/kexin type 7 · UniProt Q16549

Length
785 aa
Mass
86.2 kDa
Annotated
2026-04-29
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCSK7 encodes proprotein convertase 7 (PC7), the most evolutionarily divergent membrane-bound subtilisin/kexin-type serine protease, which cleaves diverse precursor proteins at basic-residue motifs primarily in the trans-Golgi network and endosomes to regulate neurotrophin maturation, growth factor signaling, immune peptide loading, and cell adhesion (PMID:8622945, PMID:9242622, PMID:24101515, PMID:26416966, PMID:20164418). Established enzymatic substrates include proBDNF, proVEGF-C, prohepcidin, pro-BMP4, TGFβ1a, CASC4, and HIV gp160, with substrate selectivity governed by conformation rather than primary sequence alone (PMID:24101515, PMID:12782675, PMID:18664504, PMID:19651771, PMID:24178295, PMID:32820145, PMID:10657249). PC7 also functions non-enzymatically: it binds apoB100 in the ER to promote VLDL secretion, and targets apoA-V for lysosomal degradation through an ER–lysosome pathway regulated by Fam20C-mediated Ser505 phosphorylation (PMID:37967646, PMID:31945259). Endosomal trafficking and substrate access depend on a cytosolic-tail EXEXXXL motif recognized by AP-2, while PC7 reaches the cell surface via a COPII-independent unconventional secretory route governed by its transmembrane domain (PMID:31915245, PMID:21075846).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Identification of PC7 as a new member of the proprotein convertase family established that mammals possess a seventh membrane-bound subtilisin/kexin protease, phylogenetically closest to yeast kexin and the most divergent mammalian convertase.

    Evidence cDNA cloning, Northern blot, in situ hybridization, and linkage analysis of human and mouse PCSK7

    PMID:8622945

    Open questions at the time
    • No enzymatic activity demonstrated in original cloning paper
    • Substrate repertoire unknown
    • Subcellular site of action undefined
  2. 1997 High

    Biochemical characterization revealed that PC7 is a calcium-dependent serine protease with furin-like pH optimum, resolving whether the newly cloned gene encoded an active enzyme and defining its basic enzymology.

    Evidence Vaccinia virus overexpression in BSC40 cells with fluorogenic substrates and in vitro peptide cleavage; also shown to cleave HIV gp160 in cell-based assays

    PMID:9094426 PMID:9242622

    Open questions at the time
    • Endogenous substrates not yet identified
    • Substrate selectivity rules not defined
  3. 1999 High

    Demonstration that the PC7 prosegment acts as a potent autoinhibitor (Ki ~7 nM for C-terminal peptide) and that its helical structure dictates inhibitory potency provided the first mechanistic understanding of PC7 zymogen activation and potential therapeutic inhibition strategies.

    Evidence Recombinant prosegment inhibition assays, NMR structure of inhibitory peptide, ex vivo blockade of proNGF/proBDNF processing

    PMID:10567353 PMID:10715106

    Open questions at the time
    • Full-length structure of mature PC7 unavailable
    • Physiological timing of prosegment release not defined
  4. 2003 High

    Identification of proVEGF-C and prohepcidin as PC7 substrates expanded PC7's physiological role beyond neurotrophins to angiogenesis/lymphangiogenesis and iron homeostasis.

    Evidence LoVo cell complementation, in vitro cleavage, and in vivo tumor model (VEGF-C); mutagenesis plus cell-based assays (hepcidin)

    PMID:12782675 PMID:18664504

    Open questions at the time
    • Relative contribution of PC7 versus furin/PACE4 on these substrates in vivo unclear
    • No PC7-selective inhibitor used
  5. 2009 High

    Demonstration of PC7's selective cleavage of the S1 site of pro-BMP4 during Xenopus embryogenesis established that PC7 has substrate-site selectivity distinct from furin/PC6, with developmental consequences.

    Evidence Antisense knockdown and PC7-selective α1-PDX inhibitor variant in Xenopus embryos

    PMID:19651771

    Open questions at the time
    • Mammalian in vivo validation of BMP4 processing by PC7 not shown
    • Structural basis for S1 selectivity unresolved
  6. 2010 High

    Discovery that mature PC7 reaches the cell surface via a COPII-independent unconventional secretory route—controlled by its transmembrane domain and accompanied by secretion of a non-inhibitory prosegment—revealed a trafficking mechanism unique among proprotein convertases.

    Evidence Brefeldin A treatment, COPII inhibition, TM-domain swaps, palmitoylation assays, electron microscopy in HEK293 cells

    PMID:21075846

    Open questions at the time
    • Identity of the unconventional trafficking machinery unknown
    • Whether palmitoylation of Cys699/Cys704 regulates other functions unaddressed
  7. 2010 High

    PC7 was shown to function in MHC class I antigen presentation by rescuing unstable peptide–MHC I complexes when the peptide-loading complex fails, establishing a non-redundant immune role for PC7 distinct from furin.

    Evidence siRNA silencing of PC7 in PLC-deficient human cells, flow cytometry, mass spectrometry of presented peptides

    PMID:20164418

    Open questions at the time
    • Direct MHC I peptide trimming substrate specificity not defined
    • In vivo immune consequences of PC7 loss not tested
  8. 2013 High

    PC7 knockout mice demonstrated that PC7 is the physiologically relevant convertase for proBDNF maturation in hippocampus and amygdala, with loss causing severe memory deficits rescuable by a TrkB agonist—providing causal in vivo evidence for PC7's neurotrophin-processing role.

    Evidence Pcsk7−/− mice, Western blot for BDNF in brain regions, behavioral testing, pharmacological rescue with 7,8-DHF

    PMID:24101515

    Open questions at the time
    • Whether PC7 loss affects other neurotrophins in vivo not examined
    • Human genetic evidence linking PCSK7 to memory disorders lacking
  9. 2013 High

    Zebrafish pcsk7 knockdown causing brain, eye, and otic vesicle defects—phenocopied by tgfβ1a morphants—established TGFβ1a as a developmental substrate and confirmed PC7's essential role in vertebrate organogenesis.

    Evidence Morpholino knockdown in zebrafish, transcriptomics, TGFβ1a cleavage assays, epistasis analysis

    PMID:24178295

    Open questions at the time
    • Morpholino off-target effects possible; genetic mutant confirmation pending
    • Whether PC7 acts cell-autonomously during development not resolved
  10. 2015 High

    Live imaging of PC7 activity during mouse preimplantation development showed that PC7, furin, and Pace4 regulate E-cadherin processing to control compaction and inner cell mass formation, demonstrating compartmentalized convertase activity in vivo.

    Evidence PC mutant mouse embryos with transgenic fluorescent reporter substrate, live imaging, E-cadherin processing assays

    PMID:26416966

    Open questions at the time
    • Relative quantitative contribution of each convertase to E-cadherin cleavage not resolved
    • Downstream signaling consequences of E-cadherin fragments uncharacterized
  11. 2018 High

    Compartment-resolved biosensor imaging showed that endogenous PC7 is active in vesicles distinct from furin-active endosomes, and that a cytosolic PLC motif controls TGN recycling but is dispensable for endosomal activity—redefining the spatial logic of PC7 versus furin substrate access.

    Evidence Compartment-targeted biosensors, PLC motif mutagenesis, substrate rescue in furin-depleted B16F1 cells

    PMID:29466742

    Open questions at the time
    • Identity of PC7-positive endosomal compartment at the molecular level undefined
    • How PC7 and furin are sorted into distinct vesicles unknown
  12. 2020 High

    Multiple studies resolved key non-enzymatic and enzymatic functions: PC7 degrades apoA-V non-enzymatically via an ER–lysosome pathway modulated by Fam20C phosphorylation at Ser505; PC7 sheds CASC4 at KR66 in endosomes/TGN to promote migration; and the EXEXXXL motif in the cytosolic tail—recognized by AP-2—governs endosomal localization and hTfR1 shedding.

    Evidence Co-IP, bafilomycin/chloroquine treatment, Pcsk7−/− mice, Fam20C kinase assays (apoA-V); N-glycoproteomics, mutagenesis, migration assays (CASC4); NMR of CT peptides, AP-2 co-IP, alanine scanning (EXEXXXL/AP-2)

    PMID:31915245 PMID:31945259 PMID:32820145

    Open questions at the time
    • Structural basis for AP-2 recognition of the EXEXXXL motif not determined
    • Whether Fam20C-mediated phosphorylation regulates enzymatic activity on other substrates unknown
    • In vivo relevance of CASC4 shedding to cancer progression not demonstrated
  13. 2023 High

    PC7 was shown to bind apoB100 in the ER independently of its catalytic activity and promote VLDL secretion; loss of PC7 diverts apoB100 to proteasomal degradation, triggering UPR, autophagy, and β-oxidation that reduce hepatic lipid accumulation and improve NAFLD outcomes in mice.

    Evidence Co-IP in hepatic cells, Pcsk7−/− mouse NAFLD model, GalNAc-ASO hepatocyte knockdown, proteasome inhibition, autophagy assays

    PMID:37967646

    Open questions at the time
    • Structural determinants of the PC7–apoB100 interaction undefined
    • Whether the non-enzymatic ER function is conserved for other secretory cargo unknown
    • Human genetic validation of PCSK7 as a NAFLD modifier lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • No full-length structure of PC7 exists, the identity of the unconventional secretory pathway carrier is unknown, and the in vivo hierarchy among enzymatic and non-enzymatic functions in specific tissues remains to be established.
  • No crystal or cryo-EM structure of PC7
  • Unconventional secretory route machinery unidentified
  • Tissue-specific conditional knockouts needed to dissect enzymatic versus non-enzymatic roles

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016787 hydrolase activity 3
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 1
Partners
AP2A1APOA5APOBBDNFCASC4FAM20CTFRCVEGFC

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 PC7 (PCSK7) was identified as a novel type I membrane-bound serine proteinase of the subtilisin/kexin family, synthesized as a prepro-PC with signal peptide, prosegment ending in cleavable RAKR, and a 747-amino acid mature form; phylogenetic analysis placed it as the most divergent mammalian convertase and closest to yeast kexin. cDNA cloning, Northern blot, in situ hybridization, linkage analysis Proceedings of the National Academy of Sciences of the United States of America High 8622945
1997 Rat PC7 is synthesized as a glycosylated zymogen (101 kDa) processed to mature PC7 (89 kDa) in the ER; it has enzymatic activity on fluorogenic peptidyl substrates with pH optimum and Ca2+ dependence similar to furin, correctly processes pro-PTH and pro-PC4 peptides, but not pro-EGF peptide. Vaccinia virus overexpression in BSC40 cells, enzymatic activity assays with fluorogenic substrates, in vitro peptide cleavage assays The Journal of biological chemistry High 9242622
1997 PC7 can cleave HIV envelope glycoprotein gp160 into gp120/gp41 in a cell-type-specific manner, similar to furin, and is expressed at higher levels in activated T4 lymphocytes; demonstrated using cell-based co-expression assays and in vitro cleavage of synthetic peptides. RT-PCR, cell-based co-expression assay in BSC40 and AtT20 cells, in vitro synthetic peptide cleavage FEBS letters Medium 9094426
1999 The prosegment of PC7 acts as a potent inhibitor of PC7 enzyme activity; recombinant bacterial prosegments inhibit PC7 in vitro and, when expressed via vaccinia virus ex vivo, inhibit processing of NGF and BDNF precursors in trans. Recombinant prosegment purification, in vitro fluorogenic peptide assays, ex vivo vaccinia virus expression, Western blotting The Journal of biological chemistry High 10567353
1999 PC7 contributes to the alpha-secretase pathway for beta-amyloid precursor protein (betaAPP): overexpression of PC7 increases APPalpha secretion and reduces Abeta40/42 levels in HEK293 cells, an effect blocked by the PC inhibitor alpha1-PDX. Transient overexpression in HEK293 cells, ELISA/Western blot for APPalpha and Abeta40/42, alpha1-PDX inhibition Journal of neurochemistry Medium 10537065
1999 PC7 is colocalized with NGF in Schwann cells, macrophages, and perivascular smooth muscle cells of the injured sciatic nerve, and furin/PC7 mRNA levels increase after nerve lesion, suggesting roles in pro-NGF processing at the injury site. Northern blot, Western blot, immunocytochemistry, in situ hybridization on nerve explants The Journal of comparative neurology Medium 9888313
2000 PC7 does not process integrin alpha subunits (pro-alpha5, alpha6, alphav) in vitro or in LoVo cells, despite similar cleavage-site primary sequences, suggesting that substrate conformation (not just sequence) governs PC7-substrate interactions. In vitro cleavage assays, overexpression in furin-deficient LoVo cells, 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 inhibitory potency arises from this folded structure involving charged (E8-R11-E15) and hydrophobic (W12, L19) side-chain interactions. Enzymatic inhibition assays, NMR structure determination with NOE restraints Biochemistry High 10715106
2003 PC7, along with furin and PC5, cleaves proVEGF-C at the dibasic motif HSIIRR227SL to generate mature VEGF-C; cleavage by these convertases promotes angiogenesis and lymphangiogenesis in vivo. Cotransfection in furin-deficient LoVo cells, in vitro fluorogenic peptide cleavage, subcutaneous injection into nude mice The Journal of clinical investigation High 12782675
2008 PC7 (along with furin, PACE4, and PC5) cleaves the prohepcidin precursor at the RRRRR59DT site to generate biologically active hepcidin peptides; site-directed mutagenesis confirmed the cleavage site, and LoVo cell rescue experiments identified the active convertases. Cell transfection, LoVo cell complementation, site-directed mutagenesis, in vitro synthetic peptide cleavage Gut High 18664504
2009 PC7 selectively cleaves the S1 site of pro-BMP4 in a developmentally regulated fashion in Xenopus embryos, distinct from furin/PC6 which cleave both S1 and S2 sites; this was established using site-selective inhibitor (alpha1-PDX variant) and antisense-mediated knockdown. Antisense gene knockdown in Xenopus oocytes/embryos, PC7-selective alpha1-PDX inhibitor variant, Western blot for BMP4 processing The Journal of biological chemistry High 19651771
2010 PC7 undergoes a unique zymogen activation in which the prosegment is primarily secreted alone as a non-inhibitory protein via the conventional Golgi-dependent pathway, while a fraction of mature PC7 reaches the cell surface via a brefeldin A- and COPII-independent unconventional secretory pathway regulated by its transmembrane domain. Two cysteines (Cys699 and Cys704) in the cytosolic tail are palmitoylated but this modification does not affect trafficking pathway choice. Brefeldin A treatment, COPII inhibition, domain-swap mutants between PC7 and furin TMCT, electron microscopy, palmitoylation assays, sulfation assays The Journal of biological chemistry High 21075846
2010 PC7 is required for a second quality control checkpoint that rescues unstable MHC class I complexes after the peptide-loading complex (PLC) fails; PC7 knockdown in PLC-malfunctioning cells causes reduced MHC I surface levels and routes MHC I to lysosomes for degradation. PC7 can also directly liberate MHC I epitopes from peptide precursors. Furin is dispensable for this function. siRNA silencing of PC7, flow cytometry for MHC I surface levels, mass spectrometry of presented peptides, exogenous peptide precursor assays Journal of immunology High 20164418
2011 PC7 enhances EGF receptor pathway activation by processing the membrane-bound EGF precursor (pro-EGF) into an ~115-kDa transmembrane form (EGF-115) at an unusual VHPR290↓A motif; site-directed mutagenesis showed Arg290 is not critical, implicating indirect cleavage via PC7-activated latent serine and/or cysteine protease(s). EGF-115 shows stronger EGFR activation (elevated phospho-ERK1/2). Co-expression, site-directed mutagenesis, protease inhibitor profiling, ERK1/2 phosphorylation assays The Journal of biological chemistry High 21209099
2012 PC7 is internalized from the plasma membrane via clathrin-coated vesicles; internalization requires a novel motif in the cytoplasmic tail between Ala713 and Cys726, with Pro, Leu, and Cys identified as essential residues by alanine scanning mutagenesis. Hypertonic inhibition, Pitstop 2 inhibitor, clathrin-coated vesicle isolation, antibody uptake assays, surface biotinylation, alanine scanning mutagenesis The Journal of biological chemistry High 22294700
2013 PC7 processes proBDNF into mature BDNF; in PC7 KO mice, mature BDNF protein levels are reduced in hippocampus and amygdala. PC7 KO mice exhibit severely impaired episodic and emotional memory that is rescued by the TrkB agonist 7,8-dihydroxyflavone. PC7 knockout mice, co-expression in COS-1 cells, primary hepatocyte culture, Western blot for BDNF, behavioral testing, pharmacological rescue Proceedings of the National Academy of Sciences of the United States of America High 24101515
2013 PCSK7 is essential for zebrafish development; morpholino-mediated PCSK7 knockdown causes defects in brain, eye, and otic vesicle leading to mortality within 7 days. PCSK7 contributes to mRNA expression and proteolytic cleavage of TGFβ1a; tgfβ1a morphants phenocopy pcsk7 morphants. Morpholino knockdown in zebrafish, genome-wide gene expression analysis, TGFβ1a cleavage assays, phenotypic analysis The Journal of biological chemistry High 24178295
2015 PC7, along with furin and Pace4, regulates E-cadherin processing to control cell-cell adhesion during morula compaction and inner cell mass formation in mouse blastocysts; live imaging of a transgenic reporter substrate showed PC7 activity in inner and outer cells in partially non-overlapping compartments. PC mutant mouse embryos, live imaging with transgenic fluorescent reporter substrate, E-cadherin processing assays The Journal of cell biology High 26416966
2018 Endogenous PC7, unlike overexpressed PC7, is active in distinct vesicles separable from Furin-active endosomes. A PLC motif in the cytosolic tail of PC7 is dispensable for endosomal activity but required for TGN recycling and to rescue proActivin-A cleavage in Furin-depleted cells. PC7 cleaves Notch1 independently of PLC-mediated TGN access. Compartment-targeted biosensors, inhibitor profiling, PLC motif mutagenesis, substrate complementation assays in Furin-depleted B16F1 cells Cell reports High 29466742
2019 In HepG2 cells, PCSK7 deletion reduces lipogenesis, fat accumulation, inflammation, TGF-β pathway activation, and fibrogenesis; hepatic PCSK7 expression correlates with lipogenic gene expression. CRISPR/siRNA deletion in HepG2 cells, transcriptomic analysis, lipid accumulation assays Journal of lipid research Medium 30918065
2020 PC7 binds to and enhances lysosomal degradation of apoA-V in a nonenzymatic fashion; ER-retained forms of PC7 also degrade apoA-V via an ER-lysosomal communication inhibited by bafilomycin A1. The R504H natural variant enhances Ser505 phosphorylation by secretory kinase Fam20C; phosphomimetic PC7-S505E shows reduced apoA-V degradation. In Pcsk7-/- mice, plasma apoA-V and adipocyte LpL activity are increased. Co-expression and co-IP in HuH7 cells, bafilomycin A1/chloroquine/NH4Cl treatment, Pcsk7-/- mouse studies, in vitro kinase assay with Fam20C The FEBS journal High 31945259
2020 PC7 and furin shed Cancer Susceptibility Candidate 4 (CASC4) at the KR66↓NS site in acidic endosomes and/or the trans-Golgi network; shedding of CASC4 disrupts its anti-migratory role and generates a membrane-bound N-terminal fragment that promotes podosome-like structures, increased cellular migration and invasion. Quantitative N-glycoproteomics screen, site-directed mutagenesis, siRNA silencing, migration/invasion assays, paxillin focal adhesion staining, compartment-specific activity assays Cell death & disease High 32820145
2020 A novel EXEXXXL725 motif in the cytosolic tail of PC7 is critical for its endosomal activity on human transferrin receptor 1 (hTfR1): Glu-719, Glu-721, and Leu-725 are essential for hTfR1 shedding; Leu-725 specifically enhances PC7 localization to early endosomes; the motif is recognized by adaptor protein 2 (AP-2). Deletion of the transmembrane-cytosolic tail abolishes hTfR1 shedding. CT deletion and alanine mutagenesis, NMR of 14-mer peptides, immunocytochemistry, AP-2 co-IP, hTfR1 shedding assays The Journal of biological chemistry High 31915245
2022 miR-125a-5p, miR-143-3p, and miR-409-3p directly bind the 3'-UTR of PCSK7 mRNA and reduce PC7 expression; overexpression of miR-125a-5p in Huh7 cells inhibits PC7 protein expression and its ability to cleave human transferrin receptor 1. Dual-luciferase reporter assay, qPCR, Western blot, transferrin receptor 1 cleavage assay Metabolites Medium 35888711
2023 Independent of its proteolytic activity, membrane-bound PCSK7 binds apoB100 in the ER and enhances its secretion; loss of PCSK7/Pcsk7 leads to apoB100 degradation via ubiquitin-proteasome pathway, triggering UPR, autophagy, and β-oxidation, reducing hepatic lipid accumulation. In Pcsk7-/- mice after NAFLD diet, liver recovery is improved. GalNAc-ASO hepatocyte-targeted knockdown of Pcsk7 recapitulates these results. Co-expression, Co-IP in hepatic cell lines, Pcsk7-/- mouse NAFLD model, GalNAc-ASO knockdown, proteasome inhibition, autophagy assays Metabolism: clinical and experimental High 37967646

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components. Nature cell biology 291 22660415
2007 Role of lysophosphatidylcholine (LPC) in atherosclerosis. Current medicinal chemistry 278 18220755
2012 Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Current biology : CB 241 22521786
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 152 10337026
2011 Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors. Developmental cell 135 21664573
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 SPC4, SPC6, and the novel protease SPC7 are coexpressed with bone morphogenetic proteins at distinct sites during embryogenesis. The Journal of cell biology 85 8698813
1996 PC8 [corrected], a new member of the convertase family. The Biochemical journal 83 8615762
1997 In vitro characterization of the novel proprotein convertase PC7. The Journal of biological chemistry 74 9242622
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 72 36803990
2012 Triacylglycerol synthesis by PDAT1 in the absence of DGAT1 activity is dependent on re-acylation of LPC by LPCAT2. BMC plant biology 69 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
1997 Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160. FEBS letters 46 9094426
1984 Effects of palmitoyl carnitine and LPC on cardiac sarcolemmal Na+-K+-ATPase. The American journal of physiology 46 6093598
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
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 43 35902863
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
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
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 39 33158440
2016 Genome-wide association study of serum lipids confirms previously reported associations as well as new associations of common SNPs within PCSK7 gene with triglyceride. Journal of human genetics 38 26763881
2016 Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2. Current biology : CB 38 27618268
2010 Post-endoplasmic reticulum rescue of unstable MHC class I requires proprotein convertase PC7. Journal of immunology (Baltimore, Md. : 1950) 37 20164418
2004 The fission yeast kinetochore component Spc7 associates with the EB1 family member Mal3 and is required for kinetochore-spindle association. Molecular biology of the cell 36 15371542
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
2007 The conserved Spc7 protein is required for spindle integrity and links kinetochore complexes in fission yeast. Molecular biology of the cell 30 17442892
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 TRPM2 contributes to LPC-induced intracellular Ca2+ influx and microglial activation. Biochemical and biophysical research communications 29 28223219
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
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 28 34598017
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
2021 LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4. Frontiers in neuroscience 26 34276296
2015 TSG attenuates LPC-induced endothelial cells inflammatory damage through notch signaling inhibition. IUBMB life 26 26662286
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
2015 The vaginal isolate Lactobacillus paracasei LPC-S01 (DSM 26760) is suitable for oral administration. Frontiers in microbiology 24 26441886
2021 Astragaloside IV Inhibits Bleomycin-Induced Ferroptosis in Human Umbilical Vein Endothelial Cells by Mediating LPC. Oxidative medicine and cellular longevity 23 34760046
2018 The atherogenic actions of LPC on vascular smooth muscle cells and its LPA receptor mediated mechanism. Biochemical and biophysical research communications 23 30064908
2017 EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination. Journal of neuroinflammation 23 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
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
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 Assessment of the influence of amylose-LPC complexation on the extent of wheat starch digestibility by size-exclusion chromatography. Food chemistry 16 23993621
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
2025 ACSL1 Aggravates Thromboinflammation by LPC/LPA Metabolic Axis in Hyperlipidemia Associated Myocardial Ischemia-Reperfusion Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 39853712
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
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 13 38299357
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
2014 Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells. Molecular carcinogenesis 12 24436242
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
2022 Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development. Cell death & disease 10 36273194
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
2024 Quercetin Mitigates Lysophosphatidylcholine (LPC)-Induced Neutrophil Extracellular Traps (NETs) Formation through Inhibiting the P2X7R/P38MAPK/NOX2 Pathway. International journal of molecular sciences 9 39273358
2012 Sos7, an essential component of the conserved Schizosaccharomyces pombe Ndc80-MIND-Spc7 complex, identifies a new family of fungal kinetochore proteins. Molecular and cellular biology 9 22711988
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
2019 Agonism activities of lyso-phosphatidylcholines (LPC) Ligands binding to peroxisome proliferator-activated receptor gamma (PPARγ). Journal of biomolecular structure & dynamics 8 31025599
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
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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
1987 Detection of residual murine LPC-1 myeloma cells from bone marrow cell mixture after purging by 4-hydroperoxycyclophosphamide. Experimental hematology 6 3297761
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