Information on EC 3.4.21.B26 - proprotein convertase 5

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.B26
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
proprotein convertase 5
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
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.
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cleavage of C-N-linkage
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hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY hide
99676-46-7
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoic acid-SKKRKRRFLG-(3-nitro)-Tyr-A + H2O
2-aminobenzoic acid-SKKRKRR + FLG-(3-nitro)-Tyr-A
show the reaction diagram
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fluorogenic substrate encompassing the processing site of envelope glycoproteins of respiratory syncytial virus
-
?
2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-GGRRTRR + EAI-(3-nitro)-Tyr-A
show the reaction diagram
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fluorogenic substrate encompassing the processing site of envelope glycoproteins of ebola virus
-
?
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRERKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
-
-
-
?
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRERRRKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
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fluorogenic substrate encompassing the processing site of envelope glycoproteins of Hong Kong virus
-
?
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
-
-
-
?
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRRRKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
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-
-
?
ADAMTS-4 + H2O
?
show the reaction diagram
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-
-
-
?
endothelial lipase + H2O
?
show the reaction diagram
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-
-
-
?
human immunodeficiency virus type 1 Vpr + H2O
?
show the reaction diagram
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undergoes proteolytic processing at a very well conserved proprotein convertase cleavage site, R85QRR88-/-, proprotein convertases PC5 and PACE4 can efficiently process extracellular Vpr
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-
?
Lefty protein + H2O
?
show the reaction diagram
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-
-
-
?
PCSK9 + H2O
PCSK9-DELTAN218 + ?
show the reaction diagram
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PC5/6A inactivates PCSK9 by cleavage at the motif RFHR218
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-
?
PCSK9 + H2O
truncated PCSK9-DELTAN218 + ?
show the reaction diagram
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-
-
-
?
pGlu-Arg-Thr-Lys-Arg-methyl-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
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-
-
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?
preprohepcidin + H2O
?
show the reaction diagram
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key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
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-
?
pro-cocaine- and amphetamine-regulated transcript precursor + H2O
bioactive pro-cocaine- and amphetamine-regulated transcript I + bioactive pro-cocaine- and amphetamine-regulated transcript II + ?
show the reaction diagram
PC5/6A preferentially cleaves the pairs of basic sites, KR/KK, of the CART precursor isoforms
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-
?
pro-integrin-alpha5 + H2O
active integrin-alpha5 + ?
show the reaction diagram
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cleavage of the substrate into its heavy and light chains
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-
?
pro-integrin-alphaV + H2O
active integrin-alphaV + ?
show the reaction diagram
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cleavage of the substrate into its heavy and light chains
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-
?
pro-von Willebrand factor + H2O
von Willebrand factor + ?
show the reaction diagram
-
-
-
?
proform bone morphogenetic protein-2 + H2O
mature bone morphogenetic protein-2 + ?
show the reaction diagram
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-
-
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?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
show the reaction diagram
protein tyrosine phosphatase kappa + H2O
?
show the reaction diagram
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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
show the reaction diagram
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-
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?
pyroglutamic acid-RTKR-7-amido-4-methylcoumarin + H2O
pyroglutamic acid-RTKR + 7-amino-4-methylcoumarin
show the reaction diagram
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-
-
-
?
receptor protein tyrosine phosphatase + H2O
?
show the reaction diagram
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-
-
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?
Val-Gln-Arg-Glu-Lys-Arg-Ala-Val-Gly-Leu + H2O
?
show the reaction diagram
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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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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
human immunodeficiency virus type 1 Vpr + H2O
?
show the reaction diagram
-
undergoes proteolytic processing at a very well conserved proprotein convertase cleavage site, R85QRR88-/-, proprotein convertases PC5 and PACE4 can efficiently process extracellular Vpr
-
-
?
preprohepcidin + H2O
?
show the reaction diagram
-
key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
-
-
?
pro-integrin-alpha5 + H2O
active integrin-alpha5 + ?
show the reaction diagram
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cleavage of the substrate into its heavy and light chains
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?
pro-integrin-alphaV + H2O
active integrin-alphaV + ?
show the reaction diagram
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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 + ?
show the reaction diagram
-
-
-
-
?
proform platelet-derived growth factor A + H2O
mature platelet-derived growth factor A + ?
show the reaction diagram
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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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?
protein tyrosine phosphatase kappa + H2O
?
show the reaction diagram
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the enzyme cleaves the ectodomain of protein tyrosine phosphatase kappa
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?
additional information
?
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death at birth of the PC5/6-deficient embryos
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
14-dehydroandrographolide succinoyl monoester
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syn: SEA, 0.25 mM
alpha1-PDX
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Alpha1-proteinase inhibitor
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inhibits cleavage of Val-Gln-Arg-Glu-Lys-Arg-Ala-Val-Gly-Leu
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antitrypsin-Portland
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alpha1-antitrypsin-PDX
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D-Arg-Arg-Arg-Arg-Arg-Arg
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D-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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decanonyl-RVKR-chloromethylketone
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decanoyl-Arg-Val-Lys-Arg-chloromethylketone
hexa-D-arginine
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L-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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nona-D-arginine
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PC5-specific antisense oligonucleotide-1
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inhibits PC activity and consequently av cleavage
PC5-specific antisense oligonucleotide-2
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inhibits PC activity and consequently av cleavage, most potent inhibitor
prosegment of human furin
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Rapamycin
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strongly inhibits
transforming growth factor beta-binding protein-2
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transforming growth factor beta-binding protein-3
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0031
2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A
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pH 7, 37°C
0.0021
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A
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pH 7, 37°C
0.0051
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A
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pH 7, 37°C
0.0042
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A
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pH 7, 37°C
0.0033
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A
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pH 7, 37°C
0.0031
2-aminobenzoyl-SKKRKRRFLG-(3-nitro)-Tyr-A
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pH 7, 37°C
0.0021
pGlu-Arg-Thr-Lys-Arg-methyl-7-amido-4-methylcoumarin
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.0025
L-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00045
L-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00043
L-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.000575
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00045
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
0.00015
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37°C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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PC5A dominates
Manually annotated by BRENDA team
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PC5A dominates
Manually annotated by BRENDA team
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recombinant enzyme
Manually annotated by BRENDA team
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decidualized and undecidualized cells
Manually annotated by BRENDA team
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in the small intestine PC5/6 is mainly expressed in enterocytes
Manually annotated by BRENDA team
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nasal
Manually annotated by BRENDA team
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PC5A dominates
Manually annotated by BRENDA team
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furture hippocampus, CA3 region
Manually annotated by BRENDA team
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richest source of PC5B
Manually annotated by BRENDA team
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PC5A dominates
Manually annotated by BRENDA team
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PC5A dominates
Manually annotated by BRENDA team
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PC5 is limited to the glia and the retina of the optic nerve head
Manually annotated by BRENDA team
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PC5A dominates
Manually annotated by BRENDA team
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pancreatic and adrenal primordium
Manually annotated by BRENDA team
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PC5 is limited to the glia and the retina of the optic nerve head
Manually annotated by BRENDA team
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PC5A dominates
Manually annotated by BRENDA team
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expressed in the telencephalon at embryonic day E15.5
Manually annotated by BRENDA team
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most highly expressing PC5 line
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
trans-Golgi network
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
69000
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SDS-PAGE, PC5 of a stable transfectant in AtT-20 cells
110000
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Western blot analysis, PC5A isoform
117000
126000
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Western blot analysis, proform in decidualized endometrial stromal cells
170000
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SDS-PAGE, PC5-B isoform
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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COOH-terminal cleavage of the membrane-bound PC5-B occurs along the secretory pathway, intracellular zymogen cleavage of pro-PC5-A
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Mono Q HR column chromatography, HIC 6FF column chromatography, and Superdex 200 gel filtration
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Ni2+-column chromatography, gel filtration
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partially purified, DEAE column
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 isoforms: PC5-A and PC5-B, expressed in AtT-20 cells
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expressed in AtT-20 cells
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expressed in CHO cells
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expressed in GH3-CART cells
expressed in HEK-293 cells
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expressed in Schneider 2 cells
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expressed in Y1 cells
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real-time RT-PCR enzyme expression analysis in wild-type and enzyme knockout HEC-1-A cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decanoyl-Arg-Val-Lys-Arg-chloromethylketone decreases enzyme activity and expression
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the enzyme is up-regulated in the human endometrium specifically at the time of epithelial receptivity
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine