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PCSK6 (proprotein convertase subtilisin/kexin type 6)

Written2014-11Majid Khatib, Beatrice Demoures
University Bordeaux 1, INSERM U1029, Avenue des Facultes, Batiment B2, Talence 33405, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPACE4
paired basic amino acid cleaving system 4
Alias_symbol (synonym)SPC4
Other alias
HGNC (Hugo) PCSK6
LocusID (NCBI) 5046
Atlas_Id 41630
Location 15q26.3  [Link to chromosome band 15q26]
Location_base_pair Starts at 101303928 and ends at 101489984 bp from pter ( according to hg19-Feb_2009)  [Mapping PCSK6.png]
Fusion genes
(updated 2016)
RPL22 (1p36.31) / PCSK6 (15q26.3)

DNA/RNA

 
Description This gene can be found on chromosome 15 at location: 101844134-102029873.
Transcription The DNA sequence contains 23 exons and the transcript length: 4236 bps translated to a 968 residues protein.

Protein

 
Description PCSK6 is a member of the family of subtilisin-like proprotein convertases (PCs) that process precursor proteins at their paired basic amino acid processing sites (RXR). This protease undergoes an initial autocatalytic processing event in the endoplasmic reticulum (ER) to generate a heterodimer which exits the ER and sorts to the trans-Golgi network (TGN). In the TGN a second autocatalytic cleavage takes place in order to release an active PCSK6.
Expression PCSK6 is expressed in many tissues and encoded by different alternatively spliced mRNAs: the PACE4A-I form is secreted and expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, but at comparatively higher levels in the liver. Isoform PACE4A-II is secreted and at least expressed in placenta. Isoform PACE4B is secreted and was only found in the embryonic kidney cell line from which it was isolated. Isoforms PACE4C and PACE4D are located in ER (not secreted, remain probably inactive unprocessed form in endoplasmic reticulum) and expressed in placenta too. Isoforms PACE4E-I and PACE4E-II are probably retained intracellularly through a hydrophobic cluster in their C-terminus, and expressed in cerebellum (E-I and -II), placenta and pituitary (only E-I). The PACE4CS was also found to probably lack enzymatic activity.
Localisation PCSK6 is activated predominantly at the cell surface and able to process its substrates within the extracellular matrix and cell surface.
Function PCSK6 induce protein precursors cleavage at the R-X-(K/R)-R motif to release mature proteins. PCSK6 substrates include enzymes (ADAMTS-4 and ADAMTS-5), HIV accessory protein Vpr, NODAL, TGF-beta related proteins, proalbumin and von Willebrand factor. This protein is thought to play a role in tumor progression and left-right patterning.
Homology The PCSK6 catalytic domain has a high percentage of homology with those of the other PCs: 42% between PCSK6 and Furin.

Implicated in

Note
  
Entity Breast cancer
Note Higher expression of PCSK6 has been detected in human breast cancer. There was a correlation between the amount of PACE4 gene product and estrogen receptor content.
  
  
Entity Prostate cancer
Note A recent study demonstrated that PSCK6 was highly overexpressed in prostate cancer tissues.
  
  
Entity Skin cancer
Note Transgenic expression of PACE4 in keratinocytes of the epidermal basal layer was more susceptible to chemical carcinogenesis, evidenced by increased tumor multiplicity, tumor volume, and metastasis.
  
  
Entity Association with degree of handedness
Note There is a significant association with a VNTR polymorphism in PCSK6 and handedness.
  

Bibliography

Inhibition and transcriptional silencing of a subtilisin-like proprotein convertase, PACE4/SPC4, reduces the branching morphogenesis of and AQP5 expression in rat embryonic submandibular gland.
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PCSK6 VNTR Polymorphism Is Associated with Degree of Handedness but Not Direction of Handedness.
Arning L, Ocklenburg S, Schulz S, Ness V, Gerding WM, Hengstler JG, Falkenstein M, Epplen JT, Gunturkun O, Beste C.
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Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6).
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PMID 24845697
 
PACE4 expression in mouse basal keratinocytes results in basement membrane disruption and acceleration of tumor progression.
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The proprotein convertases furin and PACE4 play a significant role in tumor progression.
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Proprotein convertase inhibition results in decreased skin cell proliferation, tumorigenesis, and metastasis.
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PMID 20651981
 
Extraembryonic proteases regulate Nodal signalling during gastrulation.
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Nat Cell Biol. 2002 Dec;4(12):981-5.
PMID 12447384
 
Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation.
Blanchet MH, Le Good JA, Mesnard D, Oorschot V, Baflast S, Minchiotti G, Klumperman J, Constam DB.
EMBO J. 2008 Oct 8;27(19):2580-91. doi: 10.1038/emboj.2008.174. Epub 2008 Sep 4.
PMID 18772886
 
Transport and equilibrium uptake of a peptide inhibitor of PACE4 into articular cartilage is dominated by electrostatic interactions.
Byun S, Tortorella MD, Malfait AM, Fok K, Frank EH, Grodzinsky AJ.
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Role of proprotein convertases in prostate cancer progression.
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PMID 23226097
 
Knock-out mouse models of proprotein convertases: unique functions or redundancy?
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Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines.
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Identification and functional validation of CDH11, PCSK6 and SH3GL3 as novel glioma invasion-associated candidate genes.
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Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.
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Regulation of Pcsk6 expression during the preantral to antral follicle transition in mice: opposing roles of FSH and oocytes.
Diaz FJ, Sugiura K, Eppig JJ.
Biol Reprod. 2008 Jan;78(1):176-83. Epub 2007 Oct 3.
PMID 17914070
 
Enhanced UV-induced skin carcinogenesis in transgenic mice overexpressing proprotein convertases.
Fu J, Bassi DE, Zhang J, Li T, Cai KQ, Testa CL, Nicolas E, Klein-Szanto AJ.
Neoplasia. 2013 Feb;15(2):169-79.
PMID 23441131
 
Analysis of epigenetic alterations to proprotein convertase genes in disease.
Fu Y, Nachtigal MW.
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PMID 21805246
 
Endoprotease activities other than furin and PACE4 with a role in processing of HIV-I gp160 glycoproteins in CHO-K1 cells.
Inocencio NM, Sucic JF, Moehring JM, Spence MJ, Moehring TJ.
J Biol Chem. 1997 Jan 10;272(2):1344-8.
PMID 8995442
 
miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway.
Kang S, Zhao Y, Hu K, Xu C, Wang L, Liu J, Yao A, Zhang H, Cao F.
Prostate. 2014 Aug;74(11):1095-106. doi: 10.1002/pros.22822. Epub 2014 Jun 9.
PMID 24913567
 
Zebrafish ProVEGF-C expression, proteolytic processing and inhibitory effect of unprocessed ProVEGF-C during fin regeneration.
Khatib AM, Lahlil R, Scamuffa N, Akimenko MA, Ernest S, Lomri A, Lalou C, Seidah NG, Villoutreix BO, Calvo F, Siegfried G.
PLoS One. 2010 Jul 2;5(7):e11438. doi: 10.1371/journal.pone.0011438.
PMID 20625388
 
Inhibition of proprotein convertases is associated with loss of growth and tumorigenicity of HT-29 human colon carcinoma cells: importance of insulin-like growth factor-1 (IGF-1) receptor processing in IGF-1-mediated functions.
Khatib AM, Siegfried G, Prat A, Luis J, Chretien M, Metrakos P, Seidah NG.
J Biol Chem. 2001 Aug 17;276(33):30686-93. Epub 2001 Jun 11.
PMID 11402025
 
Membrane type-1 matrix metalloprotease-independent activation of pro-matrix metalloprotease-2 by proprotein convertases.
Koo BH, Kim HH, Park MY, Jeon OH, Kim DS.
FEBS J. 2009 Nov;276(21):6271-84. doi: 10.1111/j.1742-4658.2009.07335.x. Epub 2009 Sep 23.
PMID 19780834
 
Design, synthesis, and structure-activity relationship studies of a potent PACE4 inhibitor.
Kwiatkowska A, Couture F, Levesque C, Ly K, Desjardins R, Beauchemin S, Prahl A, Lammek B, Neugebauer W, Dory YL, Day R.
J Med Chem. 2014 Jan 9;57(1):98-109. doi: 10.1021/jm401457n. Epub 2013 Dec 18.
PMID 24350995
 
The potential anti-tumorigenic and anti-metastatic side of the proprotein convertases inhibitors.
Lahlil R, Calvo F, Khatib AM.
Recent Pat Anticancer Drug Discov. 2009 Jan;4(1):83-91. (REVIEW)
PMID 19149690
 
Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells' malignant phenotypes: role of tissue inhibitors of metalloproteinase-1.
Lapierre M, Siegfried G, Scamuffa N, Bontemps Y, Calvo F, Seidah NG, Khatib AM.
Cancer Res. 2007 Oct 1;67(19):9030-4.
PMID 17909005
 
The Multi-Leu peptide inhibitor discriminates between PACE4 and furin and exhibits antiproliferative effects on prostate cancer cells.
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PMID 23126600
 
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.
Lissitzky JC, Luis J, Munzer JS, Benjannet S, Parat F, Chretien M, Marvaldi J, Seidah NG.
Biochem J. 2000 Feb 15;346 Pt 1:133-8.
PMID 10657249
 
Malignant conversion of non-tumorigenic murine skin keratinocytes overexpressing PACE4.
Mahloogi H, Bassi DE, Klein-Szanto AJ.
Carcinogenesis. 2002 Apr;23(4):565-72.
PMID 11960907
 
A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype.
Malfait AM, Seymour AB, Gao F, Tortorella MD, Le Graverand-Gastineau MP, Wood LS, Doherty M, Doherty S, Zhang W, Arden NK, Vaughn FL, Leaverton PE, Spector TD, Hart DJ, Maciewicz RA, Muir KR, Das R, Sorge RE, Sotocinal SG, Schorscher-Petcu A, Valdes AM, Mogil JS.
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PMID 22440827
 
The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities.
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PMID 21896659
 
Subtilisin-like proprotein convertases, PACE4 and PC8, as well as furin, are endogenous proalbumin convertases in HepG2 cells.
Mori K, Imamaki A, Nagata K, Yonetomi Y, Kiyokage-Yoshimoto R, Martin TJ, Gillespie MT, Nagahama M, Tsuji A, Matsuda Y.
J Biochem. 1999 Mar;125(3):627-33.
PMID 10050053
 
A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus.
Mori K, Kii S, Tsuji A, Nagahama M, Imamaki A, Hayashi K, Akamatsu T, Nagamune H, Matsuda Y.
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PMID 9192737
 
Retroviral envelope glycoprotein processing: structural investigation of the cleavage site.
Moulard M, Chaloin L, Canarelli S, Mabrouk K, Darbon H.
Biochemistry. 1998 Mar 31;37(13):4510-7.
PMID 9521771
 
Maturation of HIV envelope glycoprotein precursors by cellular endoproteases.
Moulard M, Decroly E.
Biochim Biophys Acta. 2000 Nov 10;1469(3):121-32. (REVIEW)
PMID 11063880
 
Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology.
Mujoomdar ML, Hogan LM, Parlow AF, Nachtigal MW.
Reproduction. 2011 Mar;141(3):343-55. doi: 10.1530/REP-10-0451. Epub 2010 Dec 23.
PMID 21183657
 
Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4).
Nagahama M, Taniguchi T, Hashimoto E, Imamaki A, Mori K, Tsuji A, Matsuda Y.
FEBS Lett. 1998 Aug 28;434(1-2):155-9.
PMID 9738469
 
Profiling of atherosclerotic lesions by gene and tissue microarrays reveals PCSK6 as a novel protease in unstable carotid atherosclerosis.
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PMID 23908247
 
Regulation of prohepcidin processing and activity by the subtilisin-like proprotein convertases Furin, PC5, PACE4 and PC7.
Scamuffa N, Basak A, Lalou C, Wargnier A, Marcinkiewicz J, Siegfried G, Chrétien M, Calvo F, Seidah NG, Khatib AM.
Gut. 2008 Nov;57(11):1573-82. doi: 10.1136/gut.2007.141812. Epub 2008 Jul 29.
PMID 18664504
 
PCSK6 is associated with handedness in individuals with dyslexia.
Scerri TS, Brandler WM, Paracchini S, Morris AP, Ring SM, Richardson AJ, Talcott JB, Stein J, Monaco AP.
Hum Mol Genet. 2011 Feb 1;20(3):608-14. doi: 10.1093/hmg/ddq475. Epub 2010 Nov 4.
PMID 21051773
 
The proprotein convertases and their implication in sterol and/or lipid metabolism.
Seidah NG, Khatib AM, Prat A.
Biol Chem. 2006 Jul;387(7):871-7. (REVIEW)
PMID 16913836
 
The biology and therapeutic targeting of the proprotein convertases.
Seidah NG, Prat A.
Nat Rev Drug Discov. 2012 May;11(5):367-83. (REVIEW)
PMID 22679642
 
The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions.
Seidah NG, Sadr MS, Chretien M, Mbikay M.
J Biol Chem. 2013 Jul 26;288(30):21473-81. doi: 10.1074/jbc.R113.481549. Epub 2013 Jun 17. (REVIEW)
PMID 23775089
 
What lies ahead for the proprotein convertases?
Seidah NG.
Ann N Y Acad Sci. 2011 Mar;1220:149-61. doi: 10.1111/j.1749-6632.2010.05883.x. (REVIEW)
PMID 21388412
 
Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases.
Sfaxi F, Scamuffa N, Lalou C, Ma J, Metrakos P, Siegfried G, Ragg H, Bikfalvi A, Calvo F, Khatib AM.
Oncotarget. 2014 Jun 30;5(12):4195-210.
PMID 24961901
 
Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases.
Siegfried G, Basak A, Prichett-Pejic W, Scamuffa N, Ma L, Benjannet S, Veinot JP, Calvo F, Seidah N, Khatib AM.
Oncogene. 2005 Oct 20;24(46):6925-35.
PMID 16007151
 
Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain.
Sucic JF, Moehring JM, Inocencio NM, Luchini JW, Moehring TJ.
Biochem J. 1999 May 1;339 ( Pt 3):639-47.
PMID 10215603
 
A critical role for the carboxy terminal region of the proprotein convertase, PACE4A, in the regulation of its autocatalytic activation coupled with secretion.
Taniguchi T, Kuroda R, Sakurai K, Nagahama M, Wada I, Tsuji A, Matsuda Y.
Biochem Biophys Res Commun. 2002 Jan 18;290(2):878-84.
PMID 11785985
 
Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.
Tsuji A, Higashine K, Hine C, Mori K, Tamai Y, Nagamune H, Matsuda Y.
Biochem Biophys Res Commun. 1994 Apr 29;200(2):943-50.
PMID 8179631
 
Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease.
Tsuji A, Hine C, Tamai Y, Yonemoto K, Mori K, Yoshida S, Bando M, Sakai E, Mori K, Akamatsu T, Matsuda Y.
J Biochem. 1997 Aug;122(2):438-52.
PMID 9378725
 
Engineering of alpha1-antitrypsin variants selective for subtilisin-like proprotein convertases PACE4 and PC6: importance of the P2' residue in stable complex formation of the serpin with proprotein convertase.
Tsuji A, Kanie H, Makise H, Yuasa K, Nagahama M, Matsuda Y.
Protein Eng Des Sel. 2007 Apr;20(4):163-70. Epub 2007 Mar 9.
PMID 17351018
 
Secretory proprotein convertases PACE4 and PC6A are heparin-binding proteins which are localized in the extracellular matrix. Potential role of PACE4 in the activation of proproteins in the extracellular matrix.
Tsuji A, Sakurai K, Kiyokage E, Yamazaki T, Koide S, Toida K, Ishimura K, Matsuda Y.
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Human subtilisin-like proprotein convertase, PACE4 (SPC4) gene expression is highly regulated through E-box elements in HepG2 and GH4C1 cells.
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Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals.
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Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases.
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Biochem J. 1996 Mar 1;314 ( Pt 2):521-32.
PMID 8670066
 
PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFb2.
Wang Y, Wang XH, Fan DX, Zhang Y, Li MQ, Wu HX, Jin LP.
J Endocrinol. 2014 Jul;222(1):151-60. doi: 10.1530/JOE-13-0592. Epub 2014 May 23.
PMID 24860148
 
Regulation of membrane type-1 matrix metalloproteinase activation by proprotein convertases.
Yana I, Weiss SJ.
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PMID 10888676
 
Proprotein convertase PACE4 is down-regulated by the basic helix-loop-helix transcription factor hASH-1 and MASH-1.
Yoshida I, Koide S, Hasegawa SI, Nakagawara A, Tsuji A, Matsuda Y.
Biochem J. 2001 Dec 15;360(Pt 3):683-9.
PMID 11736660
 
Subtilisin-like proprotein convertase paired basic amino acid-cleaving enzyme 4 is required for chondrogenic differentiation in ATDC5 cells.
Yuasa K, Futamatsu G, Kawano T, Muroshita M, Kageyama Y, Taichi H, Ishikawa H, Nagahama M, Matsuda Y, Tsuji A.
FEBS J. 2012 Nov;279(21):3997-4009. doi: 10.1111/j.1742-4658.2012.08758.x. Epub 2012 Sep 17.
PMID 22925071
 
Subtilisin-like proprotein convertase PACE4 is required for skeletal muscle differentiation.
Yuasa K, Masuda T, Yoshikawa C, Nagahama M, Matsuda Y, Tsuji A.
J Biochem. 2009 Sep;146(3):407-15. doi: 10.1093/jb/mvp090. Epub 2009 Jun 11.
PMID 19520771
 
Transcriptional regulation of subtilisin-like proprotein convertase PACE4 by E2F: possible role of E2F-mediated upregulation of PACE4 in tumor progression.
Yuasa K, Suzue K, Nagahama M, Matsuda Y, Tsuji A.
Gene. 2007 Nov 1;402(1-2):103-10. Epub 2007 Aug 10.
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Zhong M, Benjannet S, Lazure C, Munzer S, Seidah NG.
FEBS Lett. 1996 Oct 28;396(1):31-6.
PMID 8906861
 

Citation

This paper should be referenced as such :
Khatib M, Demoures B
PCSK6 (proprotein convertase subtilisin/kexin type 6);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/PCSK6ID41630ch15q26.html


External links

Nomenclature
HGNC (Hugo)PCSK6   8569
LRG (Locus Reference Genomic)LRG_888
Cards
AtlasPCSK6ID41630ch15q26
Entrez_Gene (NCBI)PCSK6  5046  proprotein convertase subtilisin/kexin type 6
AliasesPACE4; SPC4
GeneCards (Weizmann)PCSK6
Ensembl hg19 (Hinxton)ENSG00000140479 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000140479 [Gene_View]  chr15:101303928-101489984 [Contig_View]  PCSK6 [Vega]
ICGC DataPortalENSG00000140479
TCGA cBioPortalPCSK6
AceView (NCBI)PCSK6
Genatlas (Paris)PCSK6
WikiGenes5046
SOURCE (Princeton)PCSK6
Genetics Home Reference (NIH)PCSK6
Genomic and cartography
GoldenPath hg38 (UCSC)PCSK6  -     chr15:101303928-101489984 -  15q26.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PCSK6  -     15q26.3   [Description]    (hg19-Feb_2009)
EnsemblPCSK6 - 15q26.3 [CytoView hg19]  PCSK6 - 15q26.3 [CytoView hg38]
Mapping of homologs : NCBIPCSK6 [Mapview hg19]  PCSK6 [Mapview hg38]
OMIM167405   
Gene and transcription
Genbank (Entrez)AB208955 AI478762 AL545278 AM491522 AW137040
RefSeq transcript (Entrez)NM_001291309 NM_002570 NM_138319 NM_138320 NM_138321 NM_138322 NM_138323 NM_138324 NM_138325
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PCSK6
Cluster EST : UnigeneHs.665989 [ NCBI ]
CGAP (NCI)Hs.665989
Alternative Splicing GalleryENSG00000140479
Gene ExpressionPCSK6 [ NCBI-GEO ]   PCSK6 [ EBI - ARRAY_EXPRESS ]   PCSK6 [ SEEK ]   PCSK6 [ MEM ]
Gene Expression Viewer (FireBrowse)PCSK6 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5046
GTEX Portal (Tissue expression)PCSK6
Protein : pattern, domain, 3D structure
UniProt/SwissProtP29122   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP29122  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP29122
Splice isoforms : SwissVarP29122
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.-3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   
PhosPhoSitePlusP29122
Domaine pattern : Prosite (Expaxy)P_HOMO_B (PS51829)    PLAC (PS50900)    SUBTILASE_ASP (PS00136)    SUBTILASE_HIS (PS00137)    SUBTILASE_SER (PS00138)   
Domains : Interpro (EBI)EGF-like_dom    Furin_repeat    Galactose-bd-like    GF_recep_IV    Growth_fac_rcpt_    Kexin/furin    Peptidase_S8/S53_dom    Peptidase_S8_Asp-AS    Peptidase_S8_His-AS    Peptidase_S8_Ser-AS    Peptidase_S8_subtilisin-rel    PLAC    Propept_inh    PrprotnconvertsP    S8_pro-domain   
Domain families : Pfam (Sanger)GF_recep_IV (PF14843)    P_proprotein (PF01483)    Peptidase_S8 (PF00082)    PLAC (PF08686)    S8_pro-domain (PF16470)   
Domain families : Pfam (NCBI)pfam14843    pfam01483    pfam00082    pfam08686    pfam16470   
Domain families : Smart (EMBL)EGF (SM00181)  FU (SM00261)  
Conserved Domain (NCBI)PCSK6
DMDM Disease mutations5046
Blocks (Seattle)PCSK6
SuperfamilyP29122
Human Protein AtlasENSG00000140479
Peptide AtlasP29122
HPRD01329
IPIIPI00020396   IPI00217331   IPI00217332   IPI00217333   IPI00217334   IPI00293159   IPI00982047   IPI00873584   IPI00332449   IPI00743298   
Protein Interaction databases
DIP (DOE-UCLA)P29122
IntAct (EBI)P29122
FunCoupENSG00000140479
BioGRIDPCSK6
STRING (EMBL)PCSK6
ZODIACPCSK6
Ontologies - Pathways
QuickGOP29122
Ontology : AmiGOendopeptidase activity  endopeptidase activity  serine-type endopeptidase activity  extracellular region  extracellular space  endoplasmic reticulum  Golgi lumen  plasma membrane  zygotic determination of anterior/posterior axis, embryo  determination of left/right symmetry  heparin binding  glycoprotein metabolic process  cell surface  protein processing  peptide hormone processing  regulation of BMP signaling pathway  extracellular matrix  nerve growth factor processing  nerve growth factor production  secretion by cell  lipoprotein metabolic process  nerve growth factor binding  cornification  
Ontology : EGO-EBIendopeptidase activity  endopeptidase activity  serine-type endopeptidase activity  extracellular region  extracellular space  endoplasmic reticulum  Golgi lumen  plasma membrane  zygotic determination of anterior/posterior axis, embryo  determination of left/right symmetry  heparin binding  glycoprotein metabolic process  cell surface  protein processing  peptide hormone processing  regulation of BMP signaling pathway  extracellular matrix  nerve growth factor processing  nerve growth factor production  secretion by cell  lipoprotein metabolic process  nerve growth factor binding  cornification  
REACTOMEP29122 [protein]
REACTOME PathwaysR-HSA-6809371 [pathway]   
NDEx NetworkPCSK6
Atlas of Cancer Signalling NetworkPCSK6
Wikipedia pathwaysPCSK6
Orthology - Evolution
OrthoDB5046
GeneTree (enSembl)ENSG00000140479
Phylogenetic Trees/Animal Genes : TreeFamPCSK6
HOVERGENP29122
HOGENOMP29122
Homologs : HomoloGenePCSK6
Homology/Alignments : Family Browser (UCSC)PCSK6
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPCSK6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PCSK6
dbVarPCSK6
ClinVarPCSK6
1000_GenomesPCSK6 
Exome Variant ServerPCSK6
ExAC (Exome Aggregation Consortium)PCSK6 (select the gene name)
Genetic variants : HAPMAP5046
Genomic Variants (DGV)PCSK6 [DGVbeta]
DECIPHERPCSK6 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPCSK6 
Mutations
ICGC Data PortalPCSK6 
TCGA Data PortalPCSK6 
Broad Tumor PortalPCSK6
OASIS PortalPCSK6 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPCSK6  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPCSK6
intOGen PortalPCSK6
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PCSK6
DgiDB (Drug Gene Interaction Database)PCSK6
DoCM (Curated mutations)PCSK6 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PCSK6 (select a term)
intoGenPCSK6
NCG5 (London)PCSK6
Cancer3DPCSK6(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM167405   
Orphanet
MedgenPCSK6
Genetic Testing Registry PCSK6
NextProtP29122 [Medical]
TSGene5046
GENETestsPCSK6
Target ValidationPCSK6
Huge Navigator PCSK6 [HugePedia]
snp3D : Map Gene to Disease5046
BioCentury BCIQPCSK6
ClinGenPCSK6
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5046
Chemical/Pharm GKB GenePA32895
Clinical trialPCSK6
Miscellaneous
canSAR (ICR)PCSK6 (select the gene name)
Probes
Litterature
PubMed66 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePCSK6
EVEXPCSK6
GoPubMedPCSK6
iHOPPCSK6
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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