Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.21.B24 extracted from

  • Gyamera-Acheampong, C.; Mbikay, M.
    Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review. (2009), Hum. Reprod. Update, 15, 237-247.
    View publication on PubMed

Application

Application Comment Organism
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 Mus musculus
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 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
PCSK4 is the product of a 9 kb, 15 exon gene located on chromosome 10 Mus musculus
PCSK4 is the product of a 9 kb, 15 exon gene located on chromosome 19 Homo sapiens

Protein Variants

Protein Variants Comment Organism
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 Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
plasma membrane overlying the acrosome of sperm Mus musculus 5886
-
plasma membrane the enzyme is overlying the sperm acrosome Mus musculus 5886
-
plasma membrane the enzyme is overlying the sperm acrosome Homo sapiens 5886
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
54000
-
x * 54000, SDS-APGE Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mus musculus PCSK4 appears to be a crucial enzyme for reproduction ?
-
?
additional information Mus musculus 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 ?
-
?
additional information Homo sapiens 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 ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q6UW60
-
-
Mus musculus P29121
-
-
Mus musculus P29121 C57BL/6J, PCSK4 gene is transcribed into a major mRNA and several shorter isoforms resulting from alternate splicing
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein the enzyme contains two putative N-glycosylation sites Homo sapiens
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 Homo sapiens
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 Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
germ cell predominantly expressed in male germ cells Mus musculus
-
ovary
-
Mus musculus
-
ovary
-
Homo sapiens
-
ovary macrophage-like cell Mus musculus
-
placenta
-
Mus musculus
-
placenta
-
Homo sapiens
-
sperm during spermatogenesis PCSK4 transcripts first appear at the pachetene spermatocyte stage and later disappear at the elongated spermatid stage Homo sapiens
-
sperm 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 Mus musculus
-
testis
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information PCSK4 appears to be a crucial enzyme for reproduction Mus musculus ?
-
?
additional information 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 Mus musculus ?
-
?
additional information 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 Homo sapiens ?
-
?
additional information 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 Mus musculus ?
-
?
additional information 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 Homo sapiens ?
-
?
propituitary adenylate cyclase-activating peptide + H2O
-
Mus musculus PACAP38 + PACAP27 PACAP peptides are produced during spermiogenesis, their receptors are found in Leydig cells and spermatids ?

Subunits

Subunits Comment Organism
? x * 54000, SDS-APGE Mus musculus
More 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 Mus musculus
More 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 Homo sapiens

Synonyms

Synonyms Comment Organism
More the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms Mus musculus
More the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms Homo sapiens
PC4
-
Mus musculus
PC4
-
Homo sapiens
PCSK4
-
Mus musculus
PCSK4
-
Homo sapiens
proprotein convertase subtilisin/kexin type 4
-
Mus musculus
proprotein convertase subtilisin/kexin type 4
-
Homo sapiens

General Information

General Information Comment Organism
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 Mus musculus
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 Mus musculus
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 Homo sapiens