PCSK6

PCSK6
Identifiers
Aliases	PCSK6, PACE4, SPC4, proprotein convertase subtilisin/kexin type 6
External IDs	OMIM: 167405; MGI: 102897; HomoloGene: 20569; GeneCards: PCSK6; OMA:PCSK6 - orthologs
Gene location (Human)
Chr.	Chromosome 15 (human)
End	101,525,202 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	65,700,134 bp
RNA expression pattern
	Top expressed in
	liver; ; right lobe of liver; ; middle frontal gyrus; ; corpus callosum; ; spleen; ; inferior ganglion of vagus nerve; ; inferior olivary nucleus; ; synovial joint; ; subthalamic nucleus; ; pons;
	Top expressed in
	ankle; ; calvaria; ; stria vascularis; ; lip; ; esophagus; ; left lobe of liver; ; membranous bone; ; body of femur; ; cerebellar vermis; ; maxilla;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	heparin binding; nerve growth factor binding; peptidase activity; serine-type peptidase activity; serine-type endopeptidase activity; hydrolase activity; endopeptidase activity; protein binding;
Cellular component	membrane; extracellular matrix; cell surface; endoplasmic reticulum; Golgi lumen; endomembrane system; extracellular region; extracellular space; plasma membrane; collagen-containing extracellular matrix;
Biological process	glycoprotein metabolic process; secretion by cell; protein processing; proteolysis; regulation of BMP signaling pathway; determination of left/right symmetry; peptide hormone processing; zygotic determination of anterior/posterior axis, embryo; nerve growth factor production; cornification; regulation of lipoprotein lipase activity; nerve growth factor processing;
	Sources:Amigo / QuickGO
Orthologs
	5046
	18553
	ENSG00000140479
	ENSMUSG00000030513
	P29122
	n/a
NM_138325; NM_001291309; NM_002570; NM_138319; NM_138320;
	NM_138321; NM_138322; NM_138323; NM_138324
	NM_001291184; NM_011048
NP_001278238; NP_002561; NP_612192; NP_612195; NP_612196;
	NP_612197; NP_612198
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

Proprotein convertase subtilisin/kexin type 6 is an enzyme that in humans is encoded by the PCSK6 gene.^[5]^[6] PCSK6 is a protease that cleaves NODAL into an active form to help trigger the development of left/right (LR) asymmetry.^[7] It may also be involved in left and right handedness in humans.^[8]^[9]^[10]

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.^[6]

PCSK6 also cleaves and activates corin, a serine protease that regulates sodium homeostasis and blood pressure.^[11]

Clinical significance

This gene is thought to play a role in tumor progression.^[6]

PCSK6 deficiency causes salt-sensitive hypertension in mice.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000140479 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030513 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b ^c "Entrez Gene: PCSK6 proprotein convertase subtilisin/kexin type 6".
^ Constam DB, Robertson EJ (May 1, 2000). "SPC4/PACE4 regulates a TGFbeta signaling network during axis formation". Genes & Development. 14 (9): 1146–55. doi:10.1101/gad.14.9.1146. PMC 316583. PMID 10809672.
^ 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. doi:10.1093/hmg/ddq475. PMC 3016905. PMID 21051773.
^ 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. doi:10.1371/journal.pgen.1003751. PMC 3772043. PMID 24068947.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Shore R, Covill L, Pettigrew KA, Brandler WM, Diaz R, Xu Y, Tello JA, Talcott JB, Newbury DF, Stein J, Monaco AP, Paracchini S (March 16, 2016). "The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts". Human Molecular Genetics. 25 (6): 1771–1779. doi:10.1093/hmg/ddw047. PMC 4986331. PMID 26908617.
^ ^a ^b Chen S, Cao P, Dong N, Peng J, Zhang C, Wang H, Zhou T, Yang J, Zhang Y, Martelli EE, Naga Prasad SV, Miller RE, Malfait AM, Zhou Y, Wu Q (Sep 2015). "PCSK6-mediated corin activation is essential for normal blood pressure". Nature Medicine. 21 (9): 1048–53. doi:10.1038/nm.3920. PMC 4710517. PMID 26259032.

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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.

This article on a gene on human chromosome 15 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000140479 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030513 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1741956-5] 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.

[entrez-6] "Entrez Gene: PCSK6 proprotein convertase subtilisin/kexin type 6".

[7] Constam DB, Robertson EJ (May 1, 2000). "SPC4/PACE4 regulates a TGFbeta signaling network during axis formation". Genes & Development. 14 (9): 1146–55. doi:10.1101/gad.14.9.1146. PMC 316583. PMID 10809672.

[8] 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. doi:10.1093/hmg/ddq475. PMC 3016905. PMID 21051773.

[9] 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. doi:10.1371/journal.pgen.1003751. PMC 3772043. PMID 24068947.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[10] Shore R, Covill L, Pettigrew KA, Brandler WM, Diaz R, Xu Y, Tello JA, Talcott JB, Newbury DF, Stein J, Monaco AP, Paracchini S (March 16, 2016). "The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts". Human Molecular Genetics. 25 (6): 1771–1779. doi:10.1093/hmg/ddw047. PMC 4986331. PMID 26908617.

[nm-11] Chen S, Cao P, Dong N, Peng J, Zhang C, Wang H, Zhou T, Yang J, Zhang Y, Martelli EE, Naga Prasad SV, Miller RE, Malfait AM, Zhou Y, Wu Q (Sep 2015). "PCSK6-mediated corin activation is essential for normal blood pressure". Nature Medicine. 21 (9): 1048–53. doi:10.1038/nm.3920. PMC 4710517. PMID 26259032.

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Function

Clinical significance

References

Further reading