PCSK5 explained

Proprotein convertase subtilisin/kexin type 5 is an enzyme that in humans is encoded by the PCSK5 gene, found in chromosome 9q21.3^{[1] [2] [3]} Two alternatively spliced transcripts are described for this gene but only one has its full length nature known.

Function

The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein mediates posttranslational endoproteolytic processing for several integrin alpha subunits. It is thought to process prorenin, pro-membrane type-1 matrix metalloproteinase and HIV-1 glycoprotein gp160.

Clinical significance

Mutations in this gene have been associated with Currarino syndrome-like malformations.^[4]

PCSK5 expression has been linked to higher survival rates for lung cancer patients.^[5]

Further reading

• Bassi DE, Mahloogi H, Klein-Szanto AJ . The proprotein convertases furin and PACE4 play a significant role in tumor progression . Mol. Carcinog. . 28 . 2 . 63–9 . 2000 . 10900462 . 10.1002/1098-2744(200006)28:2<63::AID-MC1>3.0.CO;2-C . 22849623 .
• Moulard M, Decroly E . Maturation of HIV envelope glycoprotein precursors by cellular endoproteases . Biochim. Biophys. Acta . 1469 . 3 . 121–32 . 2001 . 11063880 . 10.1016/S0304-4157(00)00014-9 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Campan M, Yoshizumi M, Seidah NG, Lee ME, Bianchi C, Haber E . Increased proteolytic processing of protein tyrosine phosphatase mu in confluent vascular endothelial cells: the role of PC5, a member of the subtilisin family . Biochemistry . 35 . 12 . 3797–802 . 1996 . 8620001 . 10.1021/bi952552d .
• Vollenweider F, Benjannet S, Decroly E, Savaria D, Lazure C, Thomas G, Chrétien M, Seidah NG . Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases . Biochem. J. . 314 . Pt 2 . 521–32 . 1996 . 8670066 . 1217081 . 10.1042/bj3140521.
• Miranda L, Wolf J, Pichuantes S, Duke R, Franzusoff A . Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ T lymphocytes . Proc. Natl. Acad. Sci. U.S.A. . 93 . 15 . 7695–700 . 1996 . 8755538 . 38809 . 10.1073/pnas.93.15.7695 . 1996PNAS...93.7695M . free .
• Nachtigal MW, Ingraham HA . Bioactivation of Müllerian inhibiting substance during gonadal development by a kex2/subtilisin-like endoprotease . Proc. Natl. Acad. Sci. U.S.A. . 93 . 15 . 7711–6 . 1996 . 8755541 . 38812 . 10.1073/pnas.93.15.7711 . 1996PNAS...93.7711N . free .
• Mercure C, Jutras I, Day R, Seidah NG, Reudelhuber TL . Prohormone convertase PC5 is a candidate processing enzyme for prorenin in the human adrenal cortex . Hypertension . 28 . 5 . 840–6 . 1996 . 8901832 . 10.1161/01.hyp.28.5.840 .
• De Bie I, Marcinkiewicz M, Malide D, Lazure C, Nakayama K, Bendayan M, Seidah NG . The isoforms of proprotein convertase PC5 are sorted to different subcellular compartments . J. Cell Biol. . 135 . 5 . 1261–75 . 1997 . 8947550 . 2121096 . 10.1083/jcb.135.5.1261 .
• van de Loo JW, Creemers JW, Kas K, Roebroek AJ, Van de Ven WJ . Assignment of the human proprotein convertase gene PCSK5 to chromosome 9q21.3 . Cytogenet. Cell Genet. . 75 . 4 . 227–9 . 1997 . 9067430 . 10.1159/000134489 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Moulard M, Chaloin L, Canarelli S, Mabrouk K, Darbon H, Challoin L . Retroviral envelope glycoprotein processing: structural investigation of the cleavage site . Biochemistry . 37 . 13 . 4510–7 . 1998 . 9521771 . 10.1021/bi972662f .
• Lissitzky JC, Luis J, Munzer JS, Benjannet S, Parat F, Chrétien M, Marvaldi J, Seidah NG . 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 . Biochem. J. . 346 Pt 1 . Pt 1 . 133–8 . 2000 . 10657249 . 1220832 . 10.1042/0264-6021:3460133 .
• Yana I, Weiss SJ . Regulation of Membrane Type-1 Matrix Metalloproteinase Activation by Proprotein Convertases . Mol. Biol. Cell . 11 . 7 . 2387–401 . 2000 . 10888676 . 14927 . 10.1091/mbc.11.7.2387 .
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 310948 . 10.1101/gr.143000 .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .

Notes and References

1. van de Loo JW, Creemers JW, Kas K, Roebroek AJ, Van de Ven WJ . Assignment of the human proprotein convertase gene PCSK5 to chromosome 9q21.3 . Cytogenetic and Genome Research . 75 . 4 . 227–229 . 1996 . 9067430 . 10.1159/000134489 .
2. Mbikay M, Seidah NG, Chrétien M, Simpson EM . Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human . Genomics . 26 . 1 . 123–9 . Jul 1995 . 7782070 . 10.1016/0888-7543(95)80090-9 .
3. Web site: Entrez Gene: PCSK5 proprotein convertase subtilisin/kexin type 5.
4. Szumska D, Pieles G, Essalmani R, Bilski M, Mesnard D, Kaur K, Franklyn A, El Omari K, Jefferis J, Bentham J, Taylor JM, Schneider JE, Arnold SJ, Johnson P, Tymowska-Lalanne Z, Stammers D, Clarke K, Neubauer S, Morris A, Brown SD, Shaw-Smith C, Cama A, Capra V, Ragoussis J, Constam D, Seidah NG, Prat A, Bhattacharya S . VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5 . Genes Dev. . 22 . 11 . 1465–77 . June 2008 . 18519639 . 2418583 . 10.1101/gad.479408 .
5. Web site: Research update from the MCM team (January 2024). World Community Grid. 16 January 2024. 21 May 2024.