Pcsk5

Summary

Gene Symbol: Pcsk5
Description: proprotein convertase subtilisin/kexin type 5
Alias: PC5, PC6, SPC6, b2b1549Clo, b2b585Clo, proprotein convertase subtilisin/kexin type 5, proprotein convertase 5, proprotein convertase 6, proprotein convertase PC5, subtilisin-like proprotein convertase 6, subtilisin/kexin-like protease PC5
Species: mouse
Products:     Pcsk5

Top Publications

  1. Mayer G, Hamelin J, Asselin M, Pasquato A, Marcinkiewicz E, Tang M, et al. The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates. J Biol Chem. 2008;283:2373-84 pubmed
    ..A similar mechanism may also apply to the convertase PACE4, thereby extending our knowledge of the molecular details of the zymogen activation and functions of these heparan sulfate proteoglycan-bound convertases. ..
  2. Nakagawa T, Murakami K, Nakayama K. Identification of an isoform with an extremely large Cys-rich region of PC6, a Kex2-like processing endoprotease. FEBS Lett. 1993;327:165-71 pubmed
    In the previous study [1993, J. Biochem. (Tokyo) 113, 132-135] we identified PC6, a member of the Kex2 family of processing endoproteases...
  3. Essalmani R, Zaid A, Marcinkiewicz J, Chamberland A, Pasquato A, Seidah N, et al. In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate. Proc Natl Acad Sci U S A. 2008;105:5750-5 pubmed publisher
    The proprotein convertase PC5/6 cleaves protein precursors after basic amino acids and is essential for implantation in CD1/129/Sv/C57BL/6 mixed-background mice...
  4. Essalmani R, Hamelin J, Marcinkiewicz J, Chamberland A, Mbikay M, Chretien M, et al. Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse. Mol Cell Biol. 2006;26:354-61 pubmed
    ..The Pcsk5 gene encodes two alternatively spliced isoforms, the soluble PC5A and transmembrane PC5B...
  5. Szumska D, Pieles G, Essalmani R, Bilski M, Mesnard D, Kaur K, et al. VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5. Genes Dev. 2008;22:1465-77 pubmed publisher
    ..It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6)...
  6. St Germain C, Croissandeau G, Mayne J, Baltz J, Chretien M, Mbikay M. Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development. Mol Reprod Dev. 2005;72:483-93 pubmed
    ..at subsequent stages of preimplantation embryonic development, whereas the levels of transcripts for PC4 and PC5 gradually disappeared after the 2-cell stage...
  7. Nour N, Mayer G, Mort J, Salvas A, Mbikay M, Morrison C, et al. The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases. Mol Biol Cell. 2005;16:5215-26 pubmed
    The proprotein convertases PC5, PACE4 and furin contain a C-terminal cysteine-rich domain (CRD) of unknown function...
  8. Mesnard D, Constam D. Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst. J Cell Biol. 2010;191:129-39 pubmed publisher
    ..The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo. ..
  9. Constam D, Robertson E. Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases. J Cell Biol. 1999;144:139-49 pubmed
    ..Collectively, these data show that the half-life of mature BMPs is greatly influenced by the identity of their pro regions. ..

More Information

Publications50

  1. Lusson J, Vieau D, Hamelin J, Day R, Chretien M, Seidah N. cDNA structure of the mouse and rat subtilisin/kexin-like PC5: a candidate proprotein convertase expressed in endocrine and nonendocrine cells. Proc Natl Acad Sci U S A. 1993;90:6691-5 pubmed
    ..of the known proprotein convertases (PCs) PC1, PC2, furin, and PC4, we identified a subtilisin/kexin-like PC called PC5 in both mouse and rat tissues. The composite structure (2...
  2. Nakagawa T, Hosaka M, Torii S, Watanabe T, Murakami K, Nakayama K. Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4. J Biochem. 1993;113:132-5 pubmed
    ..This cDNA encoded a 915-residue protein, designated as PC6, containing a subtilisin-like catalytic domain closely related to those of other Kex2-like members (furin, PC2, PC1/..
  3. Constam D, Calfon M, Robertson E. SPC4, SPC6, and the novel protease SPC7 are coexpressed with bone morphogenetic proteins at distinct sites during embryogenesis. J Cell Biol. 1996;134:181-91 pubmed
    ..SPC7, like SPC1, is expressed ubiquitously throughout development. In contrast, SPC4 and SPC6 exhibit dynamic expression patterns...
  4. Kalus I, Schnegelsberg B, Seidah N, Kleene R, Schachner M. The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1. J Biol Chem. 2003;278:10381-8 pubmed
    ..L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth. ..
  5. Essalmani R, Susan Resiga D, Guillemot J, Kim W, Sachan V, Awan Z, et al. Thrombin activation of protein C requires prior processing by a liver proprotein convertase. J Biol Chem. 2017;292:10564-10573 pubmed publisher
    ..present evidence that at the surface of COS-1 cells, mouse proprotein C is first cleaved by the convertases furin, PC5/6A, and PACE4...
  6. Sun X, Essalmani R, Seidah N, Prat A. The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model. Mol Cancer. 2009;8:73 pubmed publisher
    ..Since PC5/6 is highly expressed in the small intestine, the present study examined its in vivo role in intestinal ..
  7. Stankewich M, Tse W, Peters L, Ch ng Y, John K, Stabach P, et al. A widely expressed betaIII spectrin associated with Golgi and cytoplasmic vesicles. Proc Natl Acad Sci U S A. 1998;95:14158-63 pubmed
    ..Liver Golgi membranes and other vesicular compartment markers cosediment in vitro with betaIII spectrin. betaIII spectrin thus constitutes a major component of the Golgi and vesicular membrane skeletons. ..
  8. Nie G, Li Y, Wang M, Liu Y, Findlay J, Salamonsen L. Inhibiting uterine PC6 blocks embryo implantation: an obligatory role for a proprotein convertase in fertility. Biol Reprod. 2005;72:1029-36 pubmed
    ..Proprotein convertase (PC) 6 (PC6) is one of the PC endoproteases regulating protein function through posttranslational activation of precursor ..
  9. Scamuffa N, Basak A, Lalou C, Wargnier A, Marcinkiewicz J, Siegfried G, et al. Regulation of prohepcidin processing and activity by the subtilisin-like proprotein convertases Furin, PC5, PACE4 and PC7. Gut. 2008;57:1573-82 pubmed publisher
    ..cell line LoVo was restored by the expression of Furin, paired basic amino acid cleaving enzyme 4 (PACE4), PC5 or PC7...
  10. Schaner P, Todd R, Seidah N, Nillni E. Processing of prothyrotropin-releasing hormone by the family of prohormone convertases. J Biol Chem. 1997;272:19958-68 pubmed
    ..pro-TRH processing, recombinant vaccinia viruses were used to coexpress the prohormone convertases PC1, PC2, PACE4, PC5-B, furin, or control dynorphin together with rat prepro-TRH in constitutively secreting LoVo cells or in the ..
  11. Sun X, Essalmani R, Susan Resiga D, Prat A, Seidah N. Latent transforming growth factor beta-binding proteins-2 and -3 inhibit the proprotein convertase 5/6A. J Biol Chem. 2011;286:29063-73 pubmed publisher
    The basic amino acid-specific proprotein convertase 5/6 (PC5/6) is an essential secretory protease, as knock-out mice die at birth and exhibit multiple homeotic transformation defects, including impaired bone morphogenesis and lung ..
  12. Thomas J, Prakash D, Weih K, Moos M. CDMP1/GDF5 has specific processing requirements that restrict its action to joint surfaces. J Biol Chem. 2006;281:26725-33 pubmed
    ..Taken together, these observations provide a plausible mechanism for local action of CDMP1/GDF5 consistent with requirements imposed by current models of pattern formation in the developing limb. ..
  13. McColl B, Paavonen K, Karnezis T, Harris N, Davydova N, Rothacker J, et al. Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2. FASEB J. 2007;21:1088-98 pubmed
    ..The PCs furin and PC5 promote cleavage of both propeptides, whereas PC7 promotes cleavage of the C-terminal propeptide only...
  14. Dikeakos J, Mercure C, Lacombe M, Seidah N, Reudelhuber T. PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism. FEBS J. 2007;274:4094-102 pubmed
    ..PC1/3, PC2 and PC5/6A are the only members of the PC family that are targeted to dense core secretory granules, where they carry out ..
  15. Rehfeld J, Bundgaard J, Hannibal J, Zhu X, Norrbom C, Steiner D, et al. The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6. Endocrinology. 2008;149:1600-8 pubmed
    ..understand this difference, we examined the roles of the neuroendocrine prohormone convertases (PC) 1/3, PC2, and PC5/6 by measurement of proCCK, processing intermediates and bioactive, alpha-amidated, and O-sulfated CCK peptides in ..
  16. Shifley E, Cole S. Lunatic fringe protein processing by proprotein convertases may contribute to the short protein half-life in the segmentation clock. Biochim Biophys Acta. 2008;1783:2384-90 pubmed publisher
    ..of fringe proteins and find that LFNG processing is promoted by specific proprotein convertases including furin and SPC6. Mutations that alter LFNG processing increase its intracellular half-life without preventing its secretion...
  17. Rehfeld J, Zhu X, Norrbom C, Bundgaard J, Johnsen A, Nielsen J, et al. Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17. Biochem J. 2008;415:35-43 pubmed publisher
    ..Finally, the in vitro effect of recombinant PC5/6 on progastrin and progastrin fragments containing the relevant dibasic cleavage sites was also examined...
  18. Essalmani R, Susan Resiga D, Chamberland A, Abifadel M, Creemers J, Boileau C, et al. In vivo evidence that furin from hepatocytes inactivates PCSK9. J Biol Chem. 2011;286:4257-63 pubmed publisher
    ..data showed that human PCSK9 is inactivated by cleavage at Arg(218)? by the overexpressed convertases furin and PC5/6A...
  19. Marchesi C, Essalmani R, Lemarié C, Leibovitz E, Ebrahimian T, Paradis P, et al. Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy. J Mol Med (Berl). 2011;89:1103-11 pubmed publisher
    ..lacking PC5/6 precluded elucidation of its function in the adult, we generated mice in which the gene of PC5/6 (pcsk5) is specifically inactivated in endothelial cells (ecKO), which are viable and do not exhibit overt abnormalities...
  20. Essalmani R, Susan Resiga D, Chamberland A, Asselin M, Canuel M, Constam D, et al. Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes. J Biol Chem. 2013;288:26410-8 pubmed publisher
    The proprotein convertases (PCs) furin, PC5/6, and PACE4 exhibit unique and/or complementary functions...
  21. Seidah N, Chretien M, Day R. The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions. Biochimie. 1994;76:197-209 pubmed
    ..These subtilisin/kexin-like convertases were called furin/PACE, PC1/PC3, PC2, PACE4, PC4 and PC5/PC6. The analysis of the mRNA expression of these convertases in rat tissues and cell lines by Northern blot analysis ..
  22. Reynolds N, Blum A, Kitagawa K, Beinfeld M. Inhibition of PC5 expression decreases CCK secretion and increases PC2 expression. Peptides. 2006;27:901-4 pubmed
    ..One of the enzymes thought to be important for pro CCK cleavage is prohormone convertase 5 (PC5)...
  23. Rancourt S, Rancourt D. Murine subtilisin-like proteinase SPC6 is expressed during embryonic implantation, somitogenesis, and skeletal formation. Dev Genet. 1997;21:75-81 pubmed
    ..5: SPC1, SPC2, SPC3, and SPC6. In situ hybridization analysis of sectioned E6...
  24. De Bie I, Marcinkiewicz M, Malide D, Lazure C, Nakayama K, Bendayan M, et al. The isoforms of proprotein convertase PC5 are sorted to different subcellular compartments. J Cell Biol. 1996;135:1261-75 pubmed
    The proprotein convertase PC5 is encoded by multiple mRNAs, two of which give rise to the COOH-terminal variant isoforms PC5-A (915 amino acids [aa]) and PC5-B (1877 aa)...
  25. Tang M, Mikhailik A, Pauli I, Giudice L, Fazelabas A, Tulac S, et al. Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing. Endocrinology. 2005;146:5313-20 pubmed
    ..Among the known convertases, only PC5/6A processes lefty to its long form...
  26. Wickham L, Benjannet S, Marcinkiewicz E, Chretien M, Seidah N. Beta-amyloid protein converting enzyme 1 and brain-specific type II membrane protein BRI3: binding partners processed by furin. J Neurochem. 2005;92:93-102 pubmed
    ..Thus, furin efficiently processes both pro-BACE1 and its novel interacting protein pro-BRI3. ..
  27. Wang L, Yang G, Wu X. Identification of the role of a cysteine-rich region of PC6B by determining the enzymatic characteristics of its mutants. Mol Biotechnol. 2004;27:15-22 pubmed
    ..By kinetic analyses of four mutants, we found that the long Cys-rich repeats in the native form of mPC6B reduced its Vmax. These facts suggest that CRR acts as an important part of functional domain. ..
  28. Gallego Llamas J, Timms A, Geister K, Lindsay A, Beier D. Variant mapping and mutation discovery in inbred mice using next-generation sequencing. BMC Genomics. 2015;16:913 pubmed publisher
    ..As expected, the WGS strategy was more reliable, since many more ENU-induced variants were ascertained. ..
  29. Wright A, Kawakami Y, Pavan W. Mart1 is located on mouse chromosome 19 and is excluded as a candidate for ep and ru. Mamm Genome. 1997;8:377-8 pubmed
  30. Kato S, Zhang R, Roberts J. Proprotein convertases play an important role in regulating PKGI endoproteolytic cleavage and nuclear transport. Am J Physiol Lung Cell Mol Physiol. 2013;305:L130-40 pubmed publisher
    ..We observed that overexpression of PCs, furin and PC5, but not PC7, which are all expressed in SMC, increase PKGI cleavage in a dose-dependent manner in human embryonic ..
  31. Tsuda T, Iwai N, Deguchi E, Kimura O, Ono S, Furukawa T, et al. PCSK5 and GDF11 expression in the hindgut region of mouse embryos with anorectal malformations. Eur J Pediatr Surg. 2011;21:238-41 pubmed publisher
    ..GDF11 is a TGF? superfamily molecule and is cleaved and activated by proprotein convertase subtilisin/kexin 5 (PCSK5)...
  32. Van de Loo J, Creemers J, Kas K, Roebroek A, Van de Ven W. Assignment of the human proprotein convertase gene PCSK5 to chromosome 9q21.3. Cytogenet Cell Genet. 1996;75:227-9 pubmed
    The human PCSK5 gene, which encodes a subtilisin-like proprotein processing enzyme, has been mapped by analysis of somatic cell hybrids and YAC clones as well as fluorescence in situ hybridization to chromosome 9q21...
  33. Mbikay M, Seidah N, Chretien M, Simpson E. Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human. Genomics. 1995;26:123-9 pubmed
    ..The gene for PC5 (Pcsk5 locus) mapped to mouse chromosome 19 close to the Lpc1 (lipocortin-1) locus and, in human, was localized to ..
  34. Zhu X, Cao Y, Voogd K, Voodg K, Steiner D. On the processing of proghrelin to ghrelin. J Biol Chem. 2006;281:38867-70 pubmed
  35. Szumska D, Cioroch M, Keeling A, Prat A, Seidah N, Bhattacharya S. Pcsk5 is required in the early cranio-cardiac mesoderm for heart development. BMC Dev Biol. 2017;17:6 pubmed publisher
    Loss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomalies including cardiac malformations, caudal regression, pre-sacral mass, renal agenesis, anteroposterior patterning defects, and ..
  36. Rousselet E, Marcinkiewicz J, Kriz J, Zhou A, Hatten M, Prat A, et al. PCSK9 reduces the protein levels of the LDL receptor in mouse brain during development and after ischemic stroke. J Lipid Res. 2011;52:1383-91 pubmed publisher
    ..Thus, PCSK9 downregulates LDLR levels during brain development and following transient ischemic stroke in adult mice. ..
  37. Antenos M, Lei L, Xu M, Malipatil A, Kiesewetter S, Woodruff T. Role of PCSK5 expression in mouse ovarian follicle development: identification of the inhibin ?- and ?-subunits as candidate substrates. PLoS ONE. 2011;6:e17348 pubmed publisher
    ..We analyzed the expression of the proconvertases furin, PCSK5, PCSK6, and PCSK7 in the developing mouse ovary by real-time quantitative RT-PCR...
  38. Liu M, Wu G, Baysarowich J, Kavana M, Addona G, Bierilo K, et al. PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J Lipid Res. 2010;51:2611-8 pubmed publisher
  39. Wong B, Liu S, Schultz G, Rancourt D. Subtilisin proprotein convertase-6 expression in the mouse uterus during implantation and artificially induced decidualization. Mol Reprod Dev. 2002;61:453-9 pubmed
    ..This is confirmed by our observation of the movement of SPC-6 expression to the presumptive placental region, as TIMP-3 expression regresses at the implantation site. ..
  40. Decroly E, Wouters S, Di Bello C, Lazure C, Ruysschaert J, Seidah N. Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines. J Biol Chem. 1996;271:30442-50 pubmed
    ..The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the major ..
  41. Chitramuthu B, Baranowski D, Cadieux B, Rousselet E, Seidah N, Bennett H. Molecular cloning and embryonic expression of zebrafish PCSK5 co-orthologues: functional assessment during lateral line development. Dev Dyn. 2010;239:2933-46 pubmed publisher
    ..roles, we have cloned the cDNA sequences encoding two candidate zebrafish PC5 convertases (designated as PCSK5.1 and PCSK5.2) co-orthologous to the single PC5 encoding gene (PCSK5) found in mammals...