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Information on EC 3.4.21.B26 - proprotein convertase 5 and Organism(s) Homo sapiens and UniProt Accession Q92824
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3.4.21.B26 proprotein convertase 5Specify your search results
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
cleavage at the RX(K/R)R consensus motif. Release of mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-/-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys.
Synonyms
pc5/6, pcsk5, pc5/6a, pc5-a, proprotein convertase 5/6, prohormone convertase 5, proprotein convertase subtilisin/kexin type 5, pc5-b, pc5/6b, proprotein convertase 5, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
99676-46-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ANKKPPLPKRVRRQIHATPTP + H2O
ANKKPPLPKRVRR + QIHATPTP
a peptide representing alpha-dystroglycan amino acids 299-319 that encompasses the predicted PC6-cleavage site (ANKKPPLPKRVRR312-/-QIHATPTP)
-
-
?
PCSK9 + H2O
PCSK9-DELTAN218 + ?
PC5/6A inactivates PCSK9 by cleavage at the motif RFHR218
-
-
?
pro-integrin-alpha5 + H2O
active integrin-alpha5 + ?
cleavage of the substrate into its heavy and light chains
-
-
?
pro-integrin-alphaV + H2O
active integrin-alphaV + ?
cleavage of the substrate into its heavy and light chains
-
-
?
proform bone morphogenetic protein-2 + H2O
mature bone morphogenetic protein-2 + ?
-
-
-
?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
protein tyrosine phosphatase kappa + H2O
?
-
the enzyme cleaves the ectodomain of protein tyrosine phosphatase kappa
-
-
?
pyro-ERTKR-7-amido-4-methylcoumarin + H2O
pyro-ERTKR + 7-amino-4-methylcoumarin
-
-
-
-
?
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
-
-
?
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
-
-
?
alpha-dystroglycan + H2O
?
cleavage site (ANKKPPLPKRVRR312-/-QIHATPTP)
-
-
?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
activation
-
-
?
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
-
-
?
additional information
?
-
development of a high-throughput immunohistochemic assay for human proprotein convertase 5/6 for detecting uterine receptivity, method evaluation, overview
-
-
?
additional information
?
-
-
development of a high-throughput immunohistochemic assay for human proprotein convertase 5/6 for detecting uterine receptivity, method evaluation, overview
-
-
?
additional information
?
-
-
both isoforms can cleave a number of fluorogenic substrates of general formula Arg/Lys-(Xaa)n-(Arg)-, where n= 2, 4, or 6
-
-
?
additional information
?
-
-
substrate cleavage analysis. Strong preference of Arg at position P1 and P4
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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
-
-
?
pro-integrin-alpha5 + H2O
active integrin-alpha5 + ?
cleavage of the substrate into its heavy and light chains
-
-
?
pro-integrin-alphaV + H2O
active integrin-alphaV + ?
cleavage of the substrate into its heavy and light chains
-
-
?
proform bone morphogenetic protein-2 + H2O
mature bone morphogenetic protein-2 + ?
-
-
-
?
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
-
-
?
protein tyrosine phosphatase kappa + H2O
?
-
the enzyme cleaves the ectodomain of protein tyrosine phosphatase kappa
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
decreases enzyme activity and expression
Alpha1-proteinase inhibitor
-
inhibits cleavage of Val-Gln-Arg-Glu-Lys-Arg-Ala-Val-Gly-Leu
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
significant increase in PC5/6 mRNA levels in endometrial stromal cells treated with 17beta-estradiol plus medroxyprogesterone acetate during decidualization, whereas 17beta-estradiol alone has no effect
-
additional information
-
significant increase in PC5/6 mRNA levels in endometrial stromal cells treated with 17beta-estradiol plus medroxyprogesterone acetate during decidualization, whereas 17beta-estradiol alone has no effect
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000265
D-Arg-Arg-Arg-Arg-Arg-Arg
-
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
0.00043
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
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
significant increase in the expression of PC5/6A in a retinoic acid deficiency-induced squamous metaplasia model of cultured human nasal epithelial cells
highly expressed in metaplastic squamous epithelium of human nasal polyps
additional information
the enzyme is up-regulated in the human endometrium specifically at the time of epithelial receptivity
additional information
NCI-H146 cell line, NCI-H345 cell line, NCI-A520 cell line, LoVo-C5 cell line, BON-1 cell line
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
117000
Western blot analysis, mature form in decidualized endometrial stromal cells
126000
Western blot analysis, proform in decidualized endometrial stromal cells
65000
Western blot analysis, C-terminally truncated form in decidualized endometrial stromal cells
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
stable knockout of the enzyme in HEC-1-A cells by specific siRNA
additional information
-
stable knockout of the enzyme in HEC-1-A cells by specific siRNA
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Mono Q HR column chromatography, HIC 6FF column chromatography, and Superdex 200 gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
real-time RT-PCR enzyme expression analysis in wild-type and enzyme knockout HEC-1-A cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decanoyl-Arg-Val-Lys-Arg-chloromethylketone decreases enzyme activity and expression
decanoyl-Arg-Val-Lys-Arg-chloromethylketone decreases expression of PC5/6A
the enzyme is up-regulated in the human endometrium specifically at the time of epithelial receptivity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
crucial role in prorenin activation within the adrenal cortex or in HIV gp160 processing in CD4+ cells, major impact on cellular proliferation and on sexual differentiation, involvement in food metabolism
medicine
carotid atherosclerotic lesions obtained by endaterectomy contain PC5, PC5 colocalizes with av integrin
medicine
PC5 is a potential contributor to the initiation, progression, and complications of atherosclerosis and restenosis, targeting PC5 will likely provide novel anti-atherosclerosis strategies
medicine
PC5/6 plays a key role for decidualization in human endometrium and its action is necessary for prolactin production from endometrial stromal cells
medicine
PC5/6A is involved in squamous differentiation of human nasal epithelial cells, possibly through up-regulation of the BMP-2/pSmad1/5/8/p38 signaling pathway, pointing to a potential therapeutic target for the prevention of chronic airway diseases that exhibit squamous metaplasia
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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)
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
-
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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