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 (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 | 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 | 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 Maximum [Da] | Comment | Organism |
---|---|---|---|
54000 | - |
x * 54000, SDS-APGE | Mus musculus |
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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |