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Information on EC 3.4.21.B24 - proprotein convertase 4
for references in articles please use BRENDA:EC3.4.21.B24
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preliminary BRENDA-supplied EC number
EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.21 Serine endopeptidases
3.4.21.B24 proprotein convertase 4
The enzyme appears in viruses and cellular organisms
- 3.4.21.B24
- testicular
- sperm
-
acrosome
- medicine
- furin
-
sperm-egg
- pellucida
-
subtilases
-
endoproteinase
- zona
-
spermatogenic
- burgdorferi
-
borrelia
-
egg-binding
- subfertility
-
intramolecularly
- prodomain
-
pacap
showSynonyms
pcsk4, proprotein convertase subtilisin/kexin type 4, proprotein convertase 4, proprotein convertase pc4, proprotein convertase subtilisin/kexin-like 4, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PC4
PCSK4
proprotein convertase 4
proprotein convertase PC4/PCSK4
proprotein convertase subtilisin/kexin type 4
proprotein convertase subtilisin/kexin-like 4
previously known as proprotein convertase 4
additional information
additional information
the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms
additional information
the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cleaves hormones at pairs of basic amino acid residues
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
99676-46-7
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
A-disintegrin and metalloproteinase-like-1 + H2O
?
-
Substrates: -
Products: -
Products: -
?
A-disintegrin and metalloproteinase-like-2 + H2O
?
-
Substrates: -
Products: -
Products: -
?
A-disintegrin and metalloproteinase-like-3 + H2O
?
-
Substrates: -
Products: -
Products: -
?
A-disintegrin and metalloproteinase-like-5 + H2O
?
-
Substrates: -
Products: -
Products: -
?
acetyl-Arg-Lys-Lys-Arg-4-methylcoumarin-7-amide + H2O
?
-
Substrates: preferred substrate
Products: -
Products: -
?
acetyl-Arg-Ser-Lys-Arg-4-methylcoumarin-7-amide + H2O
?
-
Substrates: -
Products: -
Products: -
?
acetyl-KTKQLR-7-amido-4-methylcoumarin + H2O
acetyl-KTKQLR + 7-amino-4-methylcoumarin
-
Substrates: most efficiently and selectively cleaved
Products: -
Products: -
?
acetyl-PAKSARSVRA + H2O
acetyl-PAKSAR + SVRA
-
Substrates: sequence derived from pro-insulin growth factor
Products: -
Products: -
?
acetyl-PAKSERDVST + H2O
acetyl-PAKSER + DVST
-
Substrates: sequence derived from pro-insulin growth factor
Products: -
Products: -
?
Boc-RERR-7-amido-4-trifluoromethyl coumarin + H2O
Boc-RERR + 7-amino-4-trifluoromethyl coumarin
Substrates: -
Products: -
Products: -
?
Boc-RVRR-7-amido-4-methylcoumarin + H2O
Boc-RVRR + 7-amino-4-methylcoumarin
Q6KW60
Substrates: -
Products: -
Products: -
?
pERTKR-4-methyl coumaryl-7-amide + H2O
?
-
Substrates: exhibits a gradual increase in cleavage with the amount of PC4 used
Products: -
Products: -
?
pro-insulin growth factor-II + H2O
insulin growth factor-II
Substrates: 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)
Products: -
Products: -
?
pro-pituitary adenylate cyclase-activating polypeptide + H2O
?
-
Substrates: -
Products: -
Products: -
?
propituitary adenylate cyclase-activating peptide + H2O
PACAP38 + PACAP27
Substrates: -
Products: PACAP peptides are produced during spermiogenesis, their receptors are found in Leydig cells and spermatids
Products: PACAP peptides are produced during spermiogenesis, their receptors are found in Leydig cells and spermatids
?
RSKR-4-methylcoumarin-7-amide + H2O
RSKR + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
t-butyloxycarbonyl-RVRR-4-methyl coumaryl-7-amide + H2O
?
-
Substrates: -
Products: -
Products: -
?
tert-butyloxycarbonyl-RVRR-7-amido-4-methylcoumarin + H2O
tert-butyloxycarbonyl-RVRR + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
YQTLRRRVKRSLVVPTD + H2O
YQTLRRRVKR + SLVVPTD
-
Substrates: preferred substrate
Products: -
Products: -
?
proform acrosin-binding protein + H2O
mature acrosin-binding protein + ?
Substrates: 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
Products: -
Products: -
?
proform acrosin-binding protein + H2O
mature acrosin-binding protein + ?
Substrates: recombinant His-tagged substrate protein, the enzyme activates the substrate by processing from a 58.5 kDa precursor to a 27.5 kDa mature form. Two potential PCSK4 cleavage sites in the ACRBP sequence are KRVR-/-120-123 and KMSR-/-500-503
Products: -
Products: -
?
additional information
?
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
Substrates: recombinant PCSK4 in vitro cleaves synthetic peptide substrates after an Arg in a basic sequence context, most often after paired basic residues, but it cleaves uniquely better after a single Arg preceded by a Lys at P4
Products: -
Products: -
?
additional information
?
-
-
Substrates: recombinant PCSK4 in vitro cleaves synthetic peptide substrates after an Arg in a basic sequence context, most often after paired basic residues, but it cleaves uniquely better after a single Arg preceded by a Lys at P4
Products: -
Products: -
?
additional information
?
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: cleaves fluorogenic peptide substrates at pairs of basic residues
Products: -
Products: -
?
additional information
?
-
-
Substrates: PC4 substrates are growth factors proIGF-1 and proIGF-2, hormonal polypeptides, proPACAP, and surface proteins of the ADAM family, e.g. ADAM1 or fertilin alpha, ADAM2 or fertilin beta, ADAM3 or cyritestin, and ADAM5
Products: -
Products: -
?
additional information
?
-
-
Substrates: PC4 cleaves peptide bonds in the sequence R/K/H-X-X/R/K/-R, with X being any amino acid except cysteine, a preferred motif is KXKR
Products: -
Products: -
?
additional information
?
-
-
Substrates: no substrate: amyloid-beta precursor protein
Products: -
Products: -
?
additional information
?
-
-
Substrates: digestion of intramolecularly quenched fluorogenic peptides by PC4
Products: -
Products: -
?
additional information
?
-
Substrates: PCSK4 appears to be a crucial enzyme for reproduction
Products: -
Products: -
?
additional information
?
-
-
Substrates: PCSK4 appears to be a crucial enzyme for reproduction
Products: -
Products: -
?
additional information
?
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
Substrates: recombinant PCSK4 in vitro cleaves synthetic peptide substrates after an Arg in a basic sequence context, most often after paired basic residues, but it cleaves uniquely better after a single Arg preceded by a Lys at P4
Products: -
Products: -
?
additional information
?
-
-
Substrates: recombinant PCSK4 in vitro cleaves synthetic peptide substrates after an Arg in a basic sequence context, most often after paired basic residues, but it cleaves uniquely better after a single Arg preceded by a Lys at P4
Products: -
Products: -
?
additional information
?
-
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: cleaves fluorogenic peptide substrates at pairs of basic residues
Products: -
Products: -
?
additional information
?
-
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
proform acrosin-binding protein + H2O
mature acrosin-binding protein + ?
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: PC4 substrates are growth factors proIGF-1 and proIGF-2, hormonal polypeptides, proPACAP, and surface proteins of the ADAM family, e.g. ADAM1 or fertilin alpha, ADAM2 or fertilin beta, ADAM3 or cyritestin, and ADAM5
Products: -
Products: -
?
additional information
?
-
Substrates: PCSK4 appears to be a crucial enzyme for reproduction
Products: -
Products: -
?
additional information
?
-
-
Substrates: PCSK4 appears to be a crucial enzyme for reproduction
Products: -
Products: -
?
additional information
?
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
-
Substrates: members of the ADAM family, in particular ADAM1 or fertilin alpha, ADAM2 or fertilin beta, and ADAM3 or cyritestin, are potential substrates for PCSK4. ADAMs are biosynthesized in male germ cells as type-1 transmembrane precursor proteins and undergo a cascade of testicular and post-testicular proteolytic cleavages to their acrosomebound forms
Products: -
Products: -
?
additional information
?
-
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: proprotein convertase subtilisin/kexin type 4 is associated with glucose-regulated protein78/immunoglobulin heavy-chain binding protein. The prozymogen cannot efficiently self-activate in somatic cells
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Co2+
-
order of decreasing inhibitory effect: Cu2+, Hg2+, Zn2+, Ni2+, Co2+, 50% inhibition at 0.25 mM
CRES peptides
-
development of PC4 inhibitors based onthe CRES reactive site loop, miniserpin inhibitors, sequences, overview
-
Cu2+
-
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
-
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
-
PCSK4-Eda-1
peptidyl-(ene-diyne amino acid) derivative PAKSAR-(ene-diyne amino acid)-SVR
-
PCSK4-Eda-2
peptidyl-(ene-diyne amino acid) derivative PAKSER-(ene-diyne amino acid)-DVS
-
PCSK4-Eda-3
peptidyl-(ene-diyne amino acid) derivative RVKNKGRR-(ene-diyne amino acid)-IAY
-
PCSK4-Eda-4
peptidyl-(ene-diyne amino acid) derivative QRRVKR-(ene-diyne amino acid)-SVVVP
-
additional information
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
-
additional information
-
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
-
additional information
incorporation of enediyne functional moiety between P1 and P1' residues of a peptide substrate of a protease represents a novel and effective strategy for the design of small molecule peptidomimetic inhibitors of the cognate protease
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
prodomain rPC4101-116 peptide
-
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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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Hepatitis B
Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses.
Herpes Zoster
Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability.
Hypoglycemia
Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH: A Pilot Study.
Infertility
Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review.
Tetanus
Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.008
cystatin related epididymal spermatogenic dimer
Q6KW60
pH and temperature not specified in the publication
-
0.1
cystatin related epididymal spermatogenic monomer
Q6KW60
pH and temperature not specified in the publication
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
C57BL/6J, PCSK4 gene is transcribed into a major mRNA and several shorter isoforms resulting from alternate splicing
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
PC4 predominantely present during the first trimester, to a lesser extent during the third trimester
brenda
BLI-4 is expressed in external epithelia before and during cuticle assembly and is both intracellular and extracellular
brenda
PC4 predominantely present during the third trimester
brenda
PC4 predominantely present during the third trimester
brenda
additional information
during spermatogenesis PCSK4 transcripts first appear at the pachetene spermatocyte stage and later disappear at the elongated spermatid stage
brenda
during spermatogenesis PCSK4 transcripts first appear at the pachetene spermatocyte stage and later disappear at the elongated spermatid stage. Location on the cell surface of epididymal sperm
brenda
anti-PCSK4 antibodies bind with PCSK4 on the head of human spermatozoa
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
BLI4 appears both intracellular and extracellular
-
brenda
BLI4 appears both intracellular and extracellular
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
evolution
the enzyme belongs to the 9-member superfamily of mammalian subtilases collectively called proprotein convertases or proprotein convertase subtilisin/kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage
evolution
Q6KW60
the enzyme belongs to the 9-member superfamily of mammalian subtilases collectively called proprotein convertases or proprotein convertase subtilisin/kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage
evolution
proprotein convertase 4 is a member of a family of proprotein convertases that convert inactive precursor proteins into their mature and active forms
malfunction
inactivation of its gene in mouse does not alter spermatogenesis, but renders sperm incapable of fertilizing oocytes, resulting in part from sperm susceptibility to a premature acrosome reaction and from reduced ability to bind to the zona pellucida. In female mice, a lack of PCSK4 causes subfertility associated with impaired folliculogenesis
malfunction
PC4 knockout mice exhibit severely impaired male fertility due to premature sperm acrosome reaction
physiological function
the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms. PCSK4 appears to be a crucial enzyme for reproduction
physiological function
the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms. PCSK4 appears to be a crucial enzyme for reproduction. It stimulates the invasiveness of human placental trophoblasts in culture, suggesting that it may facilitate placentation in vivo
physiological function
-
PC4 activates everal protein precursors in the secretory pathway of mammalian reproduction system with a vital role in fertilization and sperm maturation
physiological function
the enzyme activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins
physiological function
Q6KW60
the enzyme activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins
physiological function
the enzyme is linked to mammalian fertilization and placenta growth
physiological function
cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Secretion depends on BLI-4/PCSK, in BLI-4 null mutants and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted but form large intracellular puncta. Their assembly into cuticle matrix is reduced but not entirely blocked. BLI-4 null mutants are embryonic lethal
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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). PCSK4_MOUSE
655
0
73214
Swiss-Prot
Mitochondrion (Reliability: 5)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
54000
72000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
PCSKs are biosynthesized in the endoplasmic reticulum as multidomain preproproteins consisting of an N-terminal signal peptide followed by a pro domain, a conserved catalytic domain, a P domain, and a variable C-terminal domain. After cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates. Domain structure, overview
additional information
-
PCSKs are biosynthesized in the endoplasmic reticulum as multidomain preproproteins consisting of an N-terminal signal peptide followed by a pro domain, a conserved catalytic domain, a P domain, and a variable C-terminal domain. After cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates. Domain structure, overview
additional information
PCSKs are biosynthesized in the endoplasmic reticulum as multidomain preproproteins consisting of an N-terminal signal peptide followed by a pro domain, a conserved catalytic domain, a P domain, and a variable C-terminal domain. After cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates
additional information
-
PCSKs are biosynthesized in the endoplasmic reticulum as multidomain preproproteins consisting of an N-terminal signal peptide followed by a pro domain, a conserved catalytic domain, a P domain, and a variable C-terminal domain. After cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
proteolytic modification
after cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates, mechanism
proteolytic modification
after cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates, mechanism, overview
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
PSK4 null mice of mixed 129Sv/C57BL/6J genetic background, generated by disruption of its genomic locus, are severely subfertile, phenotype, detailed overview
additional information
-
PSK4 null mice of mixed 129Sv/C57BL/6J genetic background, generated by disruption of its genomic locus, are severely subfertile, phenotype, detailed overview
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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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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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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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
medicine
-
manifold effects of proprotein convertases, influencing tumor cell proliferation, motility, adhesiveness, and invasiveness, should be exploited by further developing competitive or inhibitory therapeutic strategies that would be able to neutralize simultaneously the most salient cancer cell properties
medicine
abnormal processing of insulin growth factor-II by PC4 is involved in the pathophysiology of fetoplacental growth restriction
medicine
PCSK4 appears to be a crucial enzyme for reproduction. Alterations of PCSK4 expression or activity could be the underlying cause of some unexplained cases of human infertility. Conversely, inactivation of this protease represents a potential strategy for non-hormonal contraception
medicine
-
PC4 inhibitors may find potential therapeutic and clinical applications in male fertility
medicine
anti-PCSK4 antibodies can interfere with rat spermatozoa activity to penetrate the oocyte
additional information
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
additional information
-
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
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Seidah, N.G.; Chretien, M.
Pro-protein convertases of subtilisin/kexin family
Methods Enzymol.
244
175-188
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Mammalia, Rattus norvegicus
brenda
Basak, A.; Toure, B.B.; Lazure, C.; Mbikay, M.; Chretien, M.; Seidah, N.G.
Enzymic characterization in vitro of recombinant proprotein convertase PC4
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343
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Rattus norvegicus
brenda
De Strooper, B.; Creemers, J.W.; Moechars, D.; Huylebroeck, D.; Van De Ven, W.J.; Van Leuven, F.; Van den Berghe, H.
Amyloid precursor protein is not processed by furin, PACE 4, PC1/3, PC2, PC4 and PC5/6 of the furin family of proprotein processing enzymes
Biochim. Biophys. Acta
1246
185-188
1995
Mus musculus
brenda
Basak, S.; Chretien, M.; Mbikay, M.; Basak, A.
In vitro elucidation of substrate specificity and bioassay of proprotein convertase 4 using intramolecularly quenched fluorogenic peptides
Biochem. J.
380
505-514
2004
Mus musculus, Rattus norvegicus
brenda
Bassi, D.E.; Fu, J.; Lopez de Cicco, R.; Klein-Szanto, A.J.
Proprotein convertases: "master switches" in the regulation of tumor growth and progression
Mol. Carcinog.
44
151-161
2005
Homo sapiens
brenda
Qiu, Q.; Basak, A.; Mbikay, M.; Tsang, B.K.; Gruslin, A.
Role of pro-IGF-II processing by proprotein convertase 4 in human placental development
Proc. Natl. Acad. Sci. USA
102
11047-11052
2005
Homo sapiens (Q6UW60), Homo sapiens
brenda
Gyamera-Acheampong, C.; Tantibhedhyangkul, J.; Weerachatyanukul, W.; Tadros, H.; Xu, H.; van de Loo, J.; Pelletier, R.; Tanphaichitr, N.; Mbikay, M.
Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability
Biol. Reprod.
74
666-673
2006
Mus musculus (P29121), Mus musculus
brenda
Freyer, C.; Kilpatrick, L.M.; Salamonsen, L.A.; Nie, G.
Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium
Reproduction
133
1189-1197
2007
Homo sapiens (Q6UW60)
brenda
Gyamera-Acheampong, C.; Mbikay, M.
Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review.
Hum. Reprod. Update
15
237-247
2009
Homo sapiens (Q6UW60), Homo sapiens, Mus musculus (P29121), Mus musculus
brenda
Basak, A.; Shervani, N.J.; Mbikay, M.; Kolajova, M.
Recombinant proprotein convertase 4 (PC4) from Leishmania tarentolae expression system: purification, biochemical study and inhibitor design
Protein Expr. Purif.
60
117-126
2008
Rattus norvegicus
brenda
Basak, A.; Shervani, N.; Kolajova, M.; Cherla, S.; Basak, S.
Novel reactive site loop derived mini-serpin inhibitors of recombinant proprotein convertase 4
Adv. Exp. Med. Biol.
611
105-106
2009
Mammalia
brenda
Gyamera-Acheampong, C.; Sirois, F.; Denis, N.J.; Mishra, P.; Figeys, D.; Basak, A.; Mbikay, M.
The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone
Mol. Cell. Biochem.
348
43-52
2011
Homo sapiens (Q6UW60), Homo sapiens, Mus musculus, Rattus norvegicus
brenda
Mishra, P.; Qiu, Q.; Gruslin, A.; Hidaka, Y.; Mbikay, M.; Basak, A.
In vitro regulatory effect of epididymal serpin CRES on protease activity of proprotein convertase PC4/PCSK4
Curr. Mol. Med.
12
1050-1067
2012
Homo sapiens (Q6KW60), Homo sapiens, Mus musculus (P29121)
brenda
Tardif, S.; Guyonnet, B.; Cormier, N.; Cornwall, G.A.
Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice
Mol. Hum. Reprod.
18
298-307
2012
Mus musculus (P29121)
brenda
Basak, A.; Goswami, M.; Rajkumar, A.; Mitra, T.; Majumdar, S.; OReilly, P.; Bdour, H.M.; Trudeau, V.L.; Basak, A.
Enediynyl peptides and iso-coumarinyl methyl sulfones as inhibitors of proprotein convertases PCSK8/SKI-1/S1P and PCSK4/PC4 Design, synthesis and biological evaluations
Bioorg. Med. Chem. Lett.
25
2225-2237
2015
Rattus norvegicus (Q78EH2)
brenda
Logue, J.; Melville, V.M.; Ardanuy, J.; Frieman, M.B.
2,3 cyclic-nucleotide 3-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly by blocking infection-induced mitochondria depolarization
bioRxiv
0000
FEHLT
2023
Caenorhabditis elegans (P51559)
brenda
Dahril, X.S.; Aulanniam, X.S.; Keumala, V.; Mustafa, A.
Human spermatozoa anti-proprotein convertase subtilisin/kexin type 4 synthesis using New Zealand rabbit for novel immunocontraception in males
Investig. Clin. Urol.
60
303-311
2019
Homo sapiens (Q6UW60)
brenda
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