PCSK6

From Wikipedia, the free encyclopedia
Proprotein convertase subtilisin/kexin type 6
Identifiers
SymbolsPCSK6; PACE4; SPC4
External IDsOMIM: 167405 MGI: 102897 HomoloGene: 20569 ChEMBL: 2951 GeneCards: PCSK6 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez504618553
EnsemblENSG00000140479ENSMUSG00000030513
UniProtP29122F6XJP7
RefSeq (mRNA)NM_002570NM_011048
RefSeq (protein)NP_002561NP_035178
Location (UCSC)Chr 15:
101.84 – 102.07 Mb		Chr 7:
65.86 – 66.05 Mb
PubMed search
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Proprotein convertase subtilisin/kexin type 6 is an enzyme that in humans is encoded by the PCSK6 gene.[1][2] PCSK6 is a protease that cleaves NODAL into an active form to help trigger the development of left/right (LR) asymmetry.[3] It may also be involved in left and right handedness in humans.[4][5]

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.[2]

Clinical significance

This gene is thought to play a role in tumor progression.[2]

References

  1. ↑ Kiefer MC, Tucker JE, Joh R, Landsberg KE, Saltman D, Barr PJ (Jan 1992). "Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15". DNA Cell Biol 10 (10): 757–69. doi:10.1089/dna.1991.10.757. PMID 1741956. 
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: PCSK6 proprotein convertase subtilisin/kexin type 6". 
  3. ↑ Constam, DB; Robertson, EJ (May 1, 2000). "SPC4/PACE4 regulates a TGFbeta signaling network during axis formation.". Genes & development 14 (9): 1146–55. PMID 10809672. 
  4. ↑ Scerri, TS; Brandler, WM; Paracchini, S; Morris, AP; Ring, SM; Richardson, AJ; Talcott, JB; Stein, J; Monaco, AP (Feb 1, 2011). "PCSK6 is associated with handedness in individuals with dyslexia.". Human molecular genetics 20 (3): 608–14. PMID 21051773. 
  5. ↑ Brandler, WM; Morris, AP; Evans, DM; Scerri, TS; Kemp, JP; Timpson, NJ; St Pourcain, B; Smith, GD; Ring, SM; Stein, J; Monaco, AP; Talcott, JB; Fisher, SE; Webber, C; Paracchini, S (September 2013). "Common variants in left/right asymmetry genes and pathways are associated with relative hand skill.". PLoS genetics 9 (9): e1003751. PMID 24068947. 

Further reading

  • 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 et al. (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 et al. (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 et al. (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) (Pt 2): 521–32. PMC 1217081. PMID 8670066. 
  • Zhong M, Benjannet S, Lazure C et al. (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 et al. (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 et al. (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 et al. (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. PMID 9192737. 
  • Tsuji A, Hine C, Tamai Y et al. (1997). "Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease". J. Biochem. 122 (2): 438–52. PMID 9378725. 
  • Moulard M, Chaloin L, Canarelli S et al. (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 et al. (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 et al. (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 et al. (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. PMID 10050053. 
  • Sucic JF, Moehring JM, Inocencio NM et al. (1999). "Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain". Biochem. J. 339 ( Pt 3) (3): 639–47. doi:10.1042/0264-6021:3390639. PMC 1220200. PMID 10215603. 
  • Tsuji A, Yoshida S, Hasegawa S et al. (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. PMID 10467164. 


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