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alpha-dystroglycan + H2O
?
ANKKPPLPKRVRRQIHATPTP + H2O
ANKKPPLPKRVRR + QIHATPTP
a peptide representing alpha-dystroglycan amino acids 299-319 that encompasses the predicted PC6-cleavage site (ANKKPPLPKRVRR312-/-QIHATPTP)
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-
?
PCSK9 + H2O
PCSK9-DELTAN218 + ?
PC5/6A inactivates PCSK9 by cleavage at the motif RFHR218
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-
?
pro-integrin-alpha5 + H2O
active integrin-alpha5 + ?
cleavage of the substrate into its heavy and light chains
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-
?
pro-integrin-alphaV + H2O
active integrin-alphaV + ?
cleavage of the substrate into its heavy and light chains
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-
?
proform bone morphogenetic protein-2 + H2O
mature bone morphogenetic protein-2 + ?
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-
-
?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
receptor protein tyrosine phosphatase + H2O
?
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-
-
?
pGlu-Arg-Thr-Lys-Arg-methyl-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
protein tyrosine phosphatase kappa + H2O
?
-
the enzyme cleaves the ectodomain of protein tyrosine phosphatase kappa
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-
?
pyro-ERTKR-7-amido-4-methylcoumarin + H2O
pyro-ERTKR + 7-amino-4-methylcoumarin
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-
-
-
?
Val-Gln-Arg-Glu-Lys-Arg-Ala-Val-Gly-Leu + H2O
?
-
both isoforms are capable of processing the junction between gp120 and gp41 within the HIV-1 gp160 precursor
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-
?
additional information
?
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alpha-dystroglycan + H2O
?
cleavage site (ANKKPPLPKRVRR312-/-QIHATPTP). Full-length alpha-dystroglycan in the human endometrial epithelium is a barrier for embryo attachment and removal of the N-terminus by proprotein convertase 5/6 regulates receptivity. Removal of alpha-dystroglycan N-terminus is an important posttranslational control of endometrial receptivity and uterine fluid
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-
?
alpha-dystroglycan + H2O
?
cleavage site (ANKKPPLPKRVRR312-/-QIHATPTP)
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-
?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
activation
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-
?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
activation, the substrate is localized specifically to the apical surface of the luminal and glandular epithelium of uterine endometrium in the receptive phase, but barely detectable in the non-receptive phase
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-
?
additional information
?
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development of a high-throughput immunohistochemic assay for human proprotein convertase 5/6 for detecting uterine receptivity, method evaluation, overview
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?
additional information
?
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development of a high-throughput immunohistochemic assay for human proprotein convertase 5/6 for detecting uterine receptivity, method evaluation, overview
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-
?
additional information
?
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both isoforms can cleave a number of fluorogenic substrates of general formula Arg/Lys-(Xaa)n-(Arg)-, where n= 2, 4, or 6
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?
additional information
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substrate cleavage analysis. Strong preference of Arg at position P1 and P4
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?
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Adenocarcinoma
The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model.
Anorectal Malformations
Anorectal atresia and variants at predicted regulatory sites in candidate genes.
Anorectal Malformations
PCSK5 and GDF11 Expression in the Hindgut Region of Mouse Embryos with Anorectal Malformations.
Anorectal Malformations
Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
Anorectal Malformations
Spatiotemporal expression of proprotein convertase subtilisin/kexin type 5 in the development of anorectal malformations in fetal rats.
Anus, Imperforate
Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
Atherosclerosis
Proprotein convertases in human atherosclerotic plaques: the overexpression of FURIN and its substrate cytokines BAFF and APRIL.
Breast Neoplasms
Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer.
Carcinogenesis
The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model.
Cardiovascular Diseases
Genetic variation at the proprotein convertase subtilisin/kexin type 5 gene modulates high-density lipoprotein cholesterol levels.
Cardiovascular Diseases
Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy.
Colonic Neoplasms
Galectin-3 binding protein promotes cell motility in colon cancer by stimulating the shedding of protein tyrosine phosphatase kappa by proprotein convertase 5.
Endometrial Neoplasms
Proprotein convertases in post-menopausal endometrial cancer: Distinctive regulation and non-invasive diagnosis.
Esophageal Atresia
Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
Infections
The role of furin in papillomavirus infection.
Influenza in Birds
Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.
Nasal Polyps
Proprotein Convertase 5/6A is Associated with BMP-2-induced Squamous Cell Differentiation.
Neoplasm Metastasis
Implications of Proprotein Convertases in Ovarian Cancer Cell Proliferation and Tumor Progression: Insights for PACE4 as a Therapeutic Target.
Neoplasm Metastasis
Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer.
Neoplasms
Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.
Neoplasms
Comprehensive characterization of the alternative splicing landscape in head and neck squamous cell carcinoma reveals novel events associated with tumorigenesis and the immune microenvironment.
Neoplasms
Galectin-3 binding protein promotes cell motility in colon cancer by stimulating the shedding of protein tyrosine phosphatase kappa by proprotein convertase 5.
Neoplasms
Implications of Proprotein Convertases in Ovarian Cancer Cell Proliferation and Tumor Progression: Insights for PACE4 as a Therapeutic Target.
Neoplasms
Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth.
Neoplasms
Proprotein convertases in post-menopausal endometrial cancer: Distinctive regulation and non-invasive diagnosis.
Neoplasms
The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model.
Neuroinflammatory Diseases
Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix.
Osteoporosis
MicroRNA?338?3p regulates age?associated osteoporosis via targeting PCSK5.
Pheochromocytoma
PC5-A-mediated processing of pro-neurotensin in early compartments of the regulated secretory pathway of PC5-transfected PC12 cells.
Takayasu Arteritis
Genome-wide association study identifies susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in Takayasu's arteritis.
Tracheoesophageal Fistula
Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
Vaccinia
Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals.
Vaccinia
Processing of prothyrotropin-releasing hormone by the family of prohormone convertases.
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0.000265
D-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.000019
D-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.0025
L-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00045
L-Arg-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00043
L-Arg-Arg-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.000575
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00045
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00015
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
-
in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
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evolution
the enzyme belongs to the Ca2+-dependent proprotein convertase family of enzymes
evolution
the enzyme is a serine protease of the proprotein convertase family
malfunction
enzyme-knockout endometrial epithelial cells show reduced capacity to attach to trophoblast spheroids and bind to fibronectin compared with control. Knockdown of the enzyme decreases cell surface presentation of functional integrins-alpha1, alpha2, alpha5, alphaV and alphaVbeta5
malfunction
specific lentiviral short hairpin RNA-mediated PC5/6A knockdown decreases bone morphogenetic protein-2 expression and maturation, decreases expression of squamous cell markers, and increases expression of ciliated cell markers. Enzyme inhibition by decanoyl-Arg-Val-Lys-Arg-chloromethylketone and bone morphogenetic protein receptor inhibition by LDN-193189 suppress squamous differentiation, promote mucociliary differentiation, and down-regulate the BMP-2/Smad1/5/8/p38 signaling pathways
malfunction
PC6 knockdown reduces removal of alpha-dystroglycan N-terminus from endometrial epithelial cell surface and blastocyst adhesion
malfunction
specific lentiviral short hairpin RNA-mediated PC5/6A knockdown decreases BMP-2 expression and maturation, decreases expression of squamous cell markers, and increases expression of ciliated cell markers
metabolism
the enzyme in the human endometrium is tightly regulated during receptivity for embryo implantation
metabolism
the enzyme is the proprotein convertase that is tightly regulated in the uterus during embryo implantation
physiological function
involvement of the enzyme in squamous differentiation of human nasal epithelial cells possibly through up-regulation of the BMP-2/pSmad1/5/8/p38 signaling pathway
physiological function
pro-integrins-alpha in the endometrial epithelium are post-translationally cleaved by the enzyme into functional subunits for the binding of blastocyst and adhesion of extracellular matrix proteins, the enzyme is responsible for the post-translational cleavage of pro-integrin-alpha5 and integrin-alphaV into their heavy and light chains in HEC-1-A cells. The integrins are transmembrane glycoproteins, some of which play an important role in the adhesive interactions between the trophoblast (blastocyst) and uterine epithelium at implantation
physiological function
proprotein convertase 5/6 cleaves and activates platelet-derived growth factor A in the human endometrium in preparation for embryo implantation, overview. The enzyme plays an important role in converting precursor proteins into their active forms through specific proteolysis
physiological function
the enzyme is critical for receptivity establishment in women, endometrial enzyme is secreted into the uterine fluid, and levels correlate with receptivity status
physiological function
full-length alpha-dystroglycan in the human endometrial epithelium is a barrier for embryo attachment and removal of the N-terminus by proprotein convertase 5/6 regulates receptivity. Removal of alpha-dystroglycan N-terminus is an important posttranslational control of endometrial receptivity and uterine fluid
physiological function
involvement of PC5/6A in squamous differentiation of human nasal epithelial cells. Overexpression of PC5/6A and BMP-2 in the human nasal epithelial cell line RPMI-2650 demonstrates that PC5/6A can activate BMP-2
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Stawowy, P.; Kallisch, H.; Veinot, J.P.; Kilimnik, A.; Prichett, W.; Goetze, S.; Seidah, N.G.; Chretien, M.; Fleck, E.; Graf, K.
Endoproteolytic activation of av integrin by proprotein convertase PC5 is required for Vascular smooth muscle cell adhesion to vitronectin and integrin-dependent signaling
Circulation
109
770-776
2004
Homo sapiens (Q92824), Rattus norvegicus (P41413)
brenda
Seidah, N.G.; Chretien, M.
Proprotein convertase 5
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , Eds. ) Academic Press
2
1874-1877
2004
Homo sapiens, Mus musculus, Rattus norvegicus
-
brenda
Okada, H.; Nie, G.; Salamonsen, L.A.
Requirement for proprotein convertase 5/6 during decidualization of human endometrial stromal cells in vitro
J. Clin. Endocrinol. Metab.
90
1028-1034
2005
Homo sapiens (Q92824), Homo sapiens
brenda
Stawowy Philip, S.P.; Fleck Eckar, F.E.
Proprotein convertases furin and PC5: targeting atherosclerosis and restenosis at multiple levels
J. Mol. Med.
83
865-875
2005
Homo sapiens (Q92824), Rattus norvegicus (P41413)
brenda
Essalmani, R.; Hamelin, J.; Marcinkiewicz, J.; Chamberland, A.; Mbikay, M.; Chretien, M.; Seidah, N.G.; Prat, A.
Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse
Mol. Cell. Biol.
26
354-361
2006
Homo sapiens (Q92824), Mus musculus
brenda
Benjannet, S.; Rhainds, D.; Hamelin, J.; Nassoury, N.; Seidah, N.G.
The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications
J. Biol. Chem.
281
30561-30572
2006
Homo sapiens (Q92824), Homo sapiens
brenda
Fugere, M.; Appel, J.; Houghten, R.A.; Lindberg, I.; Day, R.
Short polybasic peptide sequences are potent inhibitors of PC5/6 and PC7: use of positional scanning-synthetic peptide combinatorial libraries as a tool for the optimization of inhibitory sequences
Mol. Pharmacol.
71
323-332
2007
Homo sapiens
brenda
Remacle, A.G.; Shiryaev, S.A.; Oh, E.S.; Cieplak, P.; Srinivasan, A.; Wei, G.; Liddington, R.C.; Ratnikov, B.I.; Parent, A.; Desjardins, R.; Day, R.; Smith, J.W.; Lebl, M.; Strongin, A.Y.
Substrate cleavage analysis of furin and related proprotein convertases. A comparative study
J. Biol. Chem.
283
20897-20906
2008
Homo sapiens
brenda
Fuller, J.A.; Brun-Zinkernagel, A.M.; Clark, A.F.; Wordinger, R.J.
Subtilisin-like proprotein convertase expression, localization, and activation in the human retina and optic nerve head
Invest. Ophthalmol. Vis. Sci.
50
5759-5768
2009
Homo sapiens
brenda
Kim, Y.S.; Jung, J.A.; Kim, H.J.; Ahn, Y.H.; Yoo, J.S.; Oh, S.; Cho, C.; Yoo, H.S.; Ko, J.H.
Galectin-3 binding protein promotes cell motility in colon cancer by stimulating the shedding of protein tyrosine phosphatase kappa by proprotein convertase 5
Biochem. Biophys. Res. Commun.
404
96-102
2011
Homo sapiens
brenda
Lee, S.N.; Lee, D.H.; Lee, M.G.; Yoon, J.H.
Proprotein convertase 5/6A is associated with BMP-2-induced squamous cell differentiation
Am. J. Respir. Cell Mol. Biol.
52
749-761
2014
Homo sapiens (Q92824), Homo sapiens
brenda
Heng, S.; Dynon, K.; Li, Y.; Edgell, T.; Walton, K.; Rombauts, L.J.; Vollenhoven, B.; Nie, G.
Development of a high-throughput assay for human proprotein convertase 5/6 for detecting uterine receptivity
Anal. Biochem.
475
14-21
2015
Homo sapiens (Q92824), Homo sapiens
brenda
Paule, S.; Aljofan, M.; Simon, C.; Rombauts, L.J.; Nie, G.
Cleavage of endometrial alpha-integrins into their functional forms is mediated by proprotein convertase 5/6
Hum. Reprod.
27
2766-2774
2012
Homo sapiens (Q92824), Homo sapiens
brenda
Paule, S.; Nebl, T.; Webb, A.; Vollenhoven, B.; Rombauts, L.; Nie, G.
Proprotein convertase 5/6 cleaves platelet-derived growth factor A in the human endometrium in preparation for embryo implantation
Mol. Hum. Reprod.
21
262-270
2014
Homo sapiens (Q92824), Homo sapiens
brenda
Lee, S.; Lee, D.; Lee, M.; Yoon, J.
Proprotein convertase 5/6A is associated with bone morphogenetic protein-2-induced squamous cell differentiation
Am. J. Respir. Cell Mol. Biol.
52
749-761
2015
Homo sapiens (Q92824), Homo sapiens
brenda
Heng, S.; Paule, S.G.; Li, Y.; Rombauts, L.J.; Vollenhoven, B.; Salamonsen, L.A.; Nie, G.
Posttranslational removal of alpha-dystroglycan N terminus by PC5/6 cleavage is important for uterine preparation for embryo implantation in women
FASEB J.
29
4011-4022
2015
Homo sapiens (Q92824), Homo sapiens
brenda