Information on EC 3.4.21.B24 - proprotein convertase 4

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.B24
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
proprotein convertase 4
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
cleaves hormones at pairs of basic amino acid residues
show the reaction diagram
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
99676-46-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
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
A-disintegrin and metalloproteinase-like-1 + H2O
?
show the reaction diagram
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-
-
-
?
A-disintegrin and metalloproteinase-like-2 + H2O
?
show the reaction diagram
-
-
-
-
?
A-disintegrin and metalloproteinase-like-3 + H2O
?
show the reaction diagram
-
-
-
-
?
A-disintegrin and metalloproteinase-like-5 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Arg-Lys-Lys-Arg-4-methylcoumarin-7-amide + H2O
?
show the reaction diagram
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preferred substrate
-
?
acetyl-Arg-Ser-Lys-Arg-4-methylcoumarin-7-amide + H2O
?
show the reaction diagram
-
-
-
?
acetyl-KTKQLR-7-amido-4-methylcoumarin + H2O
acetyl-KTKQLR + 7-amino-4-methylcoumarin
show the reaction diagram
-
most efficiently and selectively cleaved
-
-
?
acetyl-PAKSARSVRA + H2O
acetyl-PAKSAR + SVRA
show the reaction diagram
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sequence derived from pro-insulin growth factor
-
?
acetyl-PAKSERDVST + H2O
acetyl-PAKSER + DVST
show the reaction diagram
-
sequence derived from pro-insulin growth factor
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?
Boc-RVRR-7-amido-4-methylcoumarin + H2O
Boc-RVRR + 7-amino-4-methylcoumarin
show the reaction diagram
Q6KW60
-
-
-
?
pERTKR-4-methyl coumaryl-7-amide + H2O
?
show the reaction diagram
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exhibits a gradual increase in cleavage with the amount of PC4 used
-
-
?
pro-insulin growth factor + H2O
?
show the reaction diagram
-
-
-
?
pro-insulin growth factor-I + H2O
?
show the reaction diagram
-
-
-
-
?
pro-insulin growth factor-II + H2O
?
show the reaction diagram
-
-
-
-
?
pro-insulin growth factor-II + H2O
insulin growth factor-II
show the reaction diagram
PC4 cleaves pro-insulin growth factor-II to generate the intermediate processed form insulin growth factor-II (1-102) and, subsequently, mature insulin-growth factor-II (1-67)
-
-
?
pro-pituitary adenylate cyclase-activating polypeptide + H2O
?
show the reaction diagram
-
-
-
-
?
proform acrosin-binding protein + H2O
mature acrosin-binding protein + ?
show the reaction diagram
proform IGF-2 + H2O
mature IGF-2 + ?
show the reaction diagram
Q6KW60
-
-
-
?
propituitary adenylate cyclase-activating peptide + H2O
PACAP38 + PACAP27
show the reaction diagram
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PACAP peptides are produced during spermiogenesis, their receptors are found in Leydig cells and spermatids
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?
REKR-4-methylcoumarin-7-amide + H2O
?
show the reaction diagram
-
-
-
?
RSKR-4-methylcoumarin-7-amide + H2O
?
show the reaction diagram
-
-
-
?
RVRR-4-methylcoumarin-7-amide + H2O
?
show the reaction diagram
-
-
-
?
t-butyloxycarbonyl-RVRR-4-methyl coumaryl-7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-RVRR-7-amido-4-methylcoumarin + H2O
tert-butyloxycarbonyl-RVRR + 7-amino-4-methylcoumarin
show the reaction diagram
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-
-
-
?
YQTLRRRVKRSLVVPTD + H2O
YQTLRRRVKR + SLVVPTD
show the reaction diagram
-
preferred substrate
-
?
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
pro-insulin growth factor + H2O
?
show the reaction diagram
-
-
-
?
proform acrosin-binding protein + H2O
mature acrosin-binding protein + ?
show the reaction diagram
-
a sperm fertilization molecule located in the acrosomal matrix, the enzyme activates the substrate by processing from a 58.5 kDa precursor to a 27.5 kDa mature form
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-
?
proform IGF-2 + H2O
mature IGF-2 + ?
show the reaction diagram
Q6KW60
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-
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-chloromercuribenzoate
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strong inhibition
CDTA
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complete inhibition at 1-10 mM
Co2+
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order of decreasing inhibitory effect: Cu2+, Hg2+, Zn2+, Ni2+, Co2+, 50% inhibition at 0.25 mM
CRES peptides
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development of PC4 inhibitors based onthe CRES reactive site loop, miniserpin inhibitors, sequences, overview
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Cu2+
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order of decreasing inhibitory effect: Cu2+, Hg2+, Zn2+, Ni2+, Co2+, 50% inhibition at 0.012 mM
cystatin related epididymal spermatogenic dimer
Q6KW60
i.e. CRES, an epididymal serpin, the recombinant protein inhibits the enzyme activity in vitro in a differential manner depending on its oligomeric state, overview
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cystatin related epididymal spermatogenic monomer
Q6KW60
i.e. CRES, an epididymal serpin, the recombinant protein inhibits the enzyme activity in vitro in a differential manner depending on its oligomeric state, overview
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decanoyl-RVRK-chloromethyl ketone
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decanoyl-RVRR-chloromethyl ketone
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EDTA
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complete inhibition at 1-10 mM
EGTA
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complete inhibition at 1-10 mM
Hg2+
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order of decreasing inhibitory effect: Cu2+, Hg2+, Zn2+, Ni2+, Co2+
Ni2+
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order of decreasing inhibitory effect: Cu2+, Hg2+, Zn2+, Ni2+, Co2+
prodomain rPC4101-116 peptide
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strong competitive inhibition
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Zn2+
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order of decreasing inhibitory effect: Cu2+, Hg2+, Zn2+, Ni2+, Co2+
additional information
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inhibition of PC4 by a PC4-specific inhibitor, developed from its own prodomain sequence near the primary activation site, blocks pro-insulin growth factor-II processing and reduces trophoblast cell migration, which can be partly restored by addition of mature insulin growth factor-II
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithiothreitol
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2.5fold activation at 1 mM
prodomain rPC4101-116 peptide
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at concentrations below 0.001 mM, it enhances PC4-activity depending on concentration (by as much as about 2fold). This activation effect is less significant for a higher substrate concentration and is not noticeable at concentrations above 0.02 mM
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15
acetyl-Arg-Lys-Lys-Arg-4-methylcoumarin-7-amide
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pH 7
6.6
acetyl-Arg-Ser-Lys-Arg-4-methylcoumarin-7-amide
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pH 7
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008
cystatin related epididymal spermatogenic dimer
Q6KW60
pH and temperature not specified in the publication
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0.1
cystatin related epididymal spermatogenic monomer
Q6KW60
pH and temperature not specified in the publication
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0.0038
prodomain rPC4101-116 peptide
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000122
decanoyl-RVRK-chloromethyl ketone
Rattus norvegicus
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0.0000166
decanoyl-RVRR-chloromethyl ketone
Rattus norvegicus
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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PC4 predominantely present during the first trimester, to a lesser extent during the third trimester
Manually annotated by BRENDA team
Q6KW60
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Manually annotated by BRENDA team
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ovarian
Manually annotated by BRENDA team
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PC4 predominantely present during the third trimester
Manually annotated by BRENDA team
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PC4 predominantely present during the third trimester
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293 cells
full length and C-terminal truncated rPC4 are expressed using Leishmania tarentolae expression system
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PCSK4 is the product of a 9 kb, 15 exon gene located on chromosome 10
PCSK4 is the product of a 9 kb, 15 exon gene located on chromosome 19
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recombinant expression using the Leishmania tarentolae expression system
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stable transfection of Hi5 cells with a rat PCAA vector, infection of BSC-40 cells with a recombinant vaccinia virus carrying the rat PC4A cDNA
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information
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therapeutic targeting of PCSK4 for contraceptive purposes in man may not be associated with the endocrinological pitfalls of hormonal contraception. And PCSK4-based assays for sperm fertilizing ability is possible