PCSK7 explained

Proprotein convertase subtilisin/kexin type 7 is an enzyme that in humans is encoded by the PCSK7 gene.^{[1] [2] [3]}

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 is a calcium-dependent serine endoprotease. It is structurally related to its family members, PACE and PACE4. This protein is concentrated in the trans-Golgi network, associated with the membranes, and is not secreted. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140.

This gene has been implicated in the transcriptional regulation of housekeeping genes. Multiple alternatively spliced transcripts are described for this gene but their full length nature is not yet known. Downstream of this gene's map location at 11q23-q24, nucleotides that match part of this gene's 3' end are duplicated and inverted. A translocation breakpoint associated with lymphoma occurs between this gene and its inverted counterpart.

Further reading

• Seidah NG, Chrétien M, Day R . The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions . Biochimie . 76 . 3–4 . 197–209 . 1995 . 7819324 . 10.1016/0300-9084(94)90147-3 .
• 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.
• Tsuji A, Hine C, Mori K, etal . A novel member, PC7, of the mammalian kexin-like protease family: homology to PACE4A, its brain-specific expression and identification of isoforms . Biochem. Biophys. Res. Commun. . 202 . 3 . 1452–9 . 1994 . 8060327 . 10.1006/bbrc.1994.2094 .
• 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 .
• Meerabux J, Yaspo ML, Roebroek AJ, etal . A new member of the proprotein convertase gene family (LPC) is located at a chromosome translocation breakpoint in lymphomas . Cancer Res. . 56 . 3 . 448–51 . 1996 . 8564950 .
• Decroly E, Wouters S, Di Bello C, etal . 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. . 271 . 48 . 30442–50 . 1997 . 8940009 . 10.1074/jbc.271.48.30442 . free .
• Hallenberger S, Moulard M, Sordel M, etal . The role of eukaryotic subtilisin-like endoproteases for the activation of human immunodeficiency virus glycoproteins in natural host cells . J. Virol. . 71 . 2 . 1036–45 . 1997 . 8995623 . 10.1128/JVI.71.2.1036-1045.1997. 191154 .
• Decroly E, Benjannet S, Savaria D, Seidah NG . Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160 . FEBS Lett. . 405 . 1 . 68–72 . 1997 . 9094426 . 10.1016/S0014-5793(97)00156-7 . 40785575 . free .
• van de Loo JW, Creemers JW, Bright NA, etal . Biosynthesis, distinct post-translational modifications, and functional characterization of lymphoma proprotein convertase . J. Biol. Chem. . 272 . 43 . 27116–23 . 1997 . 9341152 . 10.1074/jbc.272.43.27116 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . 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, etal . Retroviral envelope glycoprotein processing: structural investigation of the cleavage site . Biochemistry . 37 . 13 . 4510–7 . 1998 . 9521771 . 10.1021/bi972662f .
• Mori K, Imamaki A, Nagata K, etal . Subtilisin-like proprotein convertases, PACE4 and PC8, as well as furin, are endogenous proalbumin convertases in HepG2 cells . J. Biochem. . 125 . 3 . 627–33 . 1999 . 10050053 . 10.1093/oxfordjournals.jbchem.a022329.
• Lecointe N, Meerabux J, Ebihara M, etal . Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma . Oncogene . 18 . 18 . 2852–9 . 1999 . 10362256 . 10.1038/sj.onc.1202645 . free .
• Wouters S, Decroly E, Vandenbranden M, etal . 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 Lett. . 456 . 1 . 97–102 . 1999 . 10452538 . 10.1016/S0014-5793(99)00938-2 . 7796014 . free .
• Bhattacharjya S, Xu P, Zhong M, etal . Inhibitory activity and structural characterization of a C-terminal peptide fragment derived from the prosegment of the proprotein convertase PC7 . Biochemistry . 39 . 11 . 2868–77 . 2000 . 10715106 . 10.1021/bi9923961 .
• Creemers JW, van de Loo JW, Plets E, etal . Binding of BiP to the processing enzyme lymphoma proprotein convertase prevents aggregation, but slows down maturation . J. Biol. Chem. . 275 . 49 . 38842–7 . 2001 . 10964928 . 10.1074/jbc.M006758200 . free .
• Grosset C, Chen CY, Xu N, etal . A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex . Cell . 103 . 1 . 29–40 . 2000 . 11051545 . 10.1016/S0092-8674(00)00102-1 . 18135412 . free .

Notes and References

1. Bruzzaniti A, Goodge K, Jay P, Taviaux SA, Lam MH, Berta P, Martin TJ, Moseley JM, Gillespie MT . C8, a new member of the convertase family . Biochem J . 314 (Pt 3) . Pt 3. 727–31 . Jun 1996 . 8615762 . 1217117 . 10.1042/bj3140727.
2. Goodge KA, Thomas RJ, Martin TJ, Gillespie MT . Gene organization and alternative splicing of human prohormone convertase PC8 . Biochem J . 336 (Pt 2) . Pt 2. 353–9 . Jan 1999 . 9820811 . 1219878 . 10.1042/bj3360353.
3. Web site: Entrez Gene: PCSK7 proprotein convertase subtilisin/kexin type 7.