PCSK6

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Proprotein convertase subtilisin/kexin type 6 is an enzyme that in humans is encoded by the PCSK6 gene. PCSK6 is a protease that cleaves NODAL into an active form to help trigger the development of left/right (LR) asymmetry. It may also be involved in left and right handedness in humans.

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 is a calcium-dependent serine endoprotease that can cleave precursor protein at their paired basic amino acid processing sites. Some of its substrates are - transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. Alternatively spliced transcript variants encoding different isoforms have been identified.

PCSK6 also cleaves and activates corin, a serine protease that regulates sodium homeostasis and blood pressure.

Clinical significance

This gene is thought to play a role in tumor progression.

PCSK6 deficiency causes salt-sensitive hypertension in mice.

Further reading

• Shore R, Covill L, Pettigrew KA, Diaz R, Xu Y, Tello J, Talcott J, Newbury D, Stein J, Monaco A (2016). "The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts". Hum Mol Gen. 25 (9): 1771–1779. doi:10.1093/hmg/ddw047. PMID 26604689.
• Bassi DE, Mahloogi H, Klein-Szanto AJ (2000). "The proprotein convertases furin and PACE4 play a significant role in tumor progression". Mol. Carcinog. 28 (2): 63–9. doi:10.1002/1098-2744(200006)28:2<63::AID-MC1>3.0.CO;2-C. PMID 10900462.
• Moulard M, Decroly E (2001). "Maturation of HIV envelope glycoprotein precursors by cellular endoproteases". Biochim. Biophys. Acta. 1469 (3): 121–32. doi:10.1016/S0304-4157(00)00014-9. PMID 11063880.
• Seidah NG, Prat A (2003). "Precursor convertases in the secretory pathway, cytosol and extracellular milieu". Essays Biochem. 38: 79–94. PMID 12463163.
• Tsuji A, Higashine K, Hine C, Mori K, Tamai Y, Nagamune H, Matsuda Y (1994). "Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms". Biochem. Biophys. Res. Commun. 204 (3): 1381–2. doi:10.1006/bbrc.1994.2616. PMID 7980617.
• Tsuji A, Higashine K, Hine C, Mori K, Tamai Y, Nagamune H, Matsuda Y (1994). "Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms". Biochem. Biophys. Res. Commun. 200 (2): 943–50. doi:10.1006/bbrc.1994.1541. PMID 8179631.
• Vollenweider F, Benjannet S, Decroly E, Savaria D, Lazure C, Thomas G, Chrétien M, Seidah NG (1996). "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. PMC 1217081. PMID 8670066.
• Zhong M, Benjannet S, Lazure C, Munzer S, Seidah NG (1997). "Functional analysis of human PACE4-A and PACE4-C isoforms: identification of a new PACE4-CS isoform". FEBS Lett. 396 (1): 31–6. doi:10.1016/0014-5793(96)01059-9. PMID 8906861.
• Decroly E, Wouters S, Di Bello C, Lazure C, Ruysschaert JM, Seidah NG (1997). "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. doi:10.1074/jbc.271.48.30442. PMID 8940009.
• Inocencio NM, Sucic JF, Moehring JM, Spence MJ, Moehring TJ (1997). "Endoprotease activities other than furin and PACE4 with a role in processing of HIV-I gp160 glycoproteins in CHO-K1 cells". J. Biol. Chem. 272 (2): 1344–8. doi:10.1074/jbc.272.2.1344. PMID 8995442.
• Mori K, Kii S, Tsuji A, Nagahama M, Imamaki A, Hayashi K, Akamatsu T, Nagamune H, Matsuda Y (1997). "A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus". J. Biochem. 121 (5): 941–8. doi:10.1093/oxfordjournals.jbchem.a021677. PMID 9192737.
• Tsuji A, Hine C, Tamai Y, Yonemoto K, Mori K, Yoshida S, Bando M, Sakai E, Mori K, Akamatsu T, Matsuda Y (1997). "Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease". J. Biochem. 122 (2): 438–52. doi:10.1093/oxfordjournals.jbchem.a021772. PMID 9378725.
• Moulard M, Chaloin L, Canarelli S, Mabrouk K, Darbon H, Challoin L (1998). "Retroviral envelope glycoprotein processing: structural investigation of the cleavage site". Biochemistry. 37 (13): 4510–7. doi:10.1021/bi972662f. PMID 9521771.
• Nagahama M, Taniguchi T, Hashimoto E, Imamaki A, Mori K, Tsuji A, Matsuda Y (1998). "Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4)". FEBS Lett. 434 (1–2): 155–9. doi:10.1016/S0014-5793(98)00970-3. PMID 9738469.
• Viale A, Ortola C, Hervieu G, Furuta M, Barbero P, Steiner DF, Seidah NG, Nahon JL (1999). "Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals". J. Biol. Chem. 274 (10): 6536–45. doi:10.1074/jbc.274.10.6536. PMID 10037747.
• Mori K, Imamaki A, Nagata K, Yonetomi Y, Kiyokage-Yoshimoto R, Martin TJ, Gillespie MT, Nagahama M, Tsuji A, Matsuda Y (1999). "Subtilisin-like proprotein convertases, PACE4 and PC8, as well as furin, are endogenous proalbumin convertases in HepG2 cells". J. Biochem. 125 (3): 627–33. doi:10.1093/oxfordjournals.jbchem.a022329. PMID 10050053.
• Sucic JF, Moehring JM, Inocencio NM, Luchini JW, Moehring TJ (1999). "Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain". Biochem. J. 339 (3): 639–47. doi:10.1042/0264-6021:3390639. PMC 1220200. PMID 10215603.
• Tsuji A, Yoshida S, Hasegawa S, Bando M, Yoshida I, Koide S, Mori K, Matsuda Y (2000). "Human subtilisin-like proprotein convertase, PACE4 (SPC4) gene expression is highly regulated through E-box elements in HepG2 and GH4C1 cells". J. Biochem. 126 (3): 494–502. doi:10.1093/oxfordjournals.jbchem.a022478. PMID 10467164.