Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a target for to drug development for inhibiting the PCSK9 processing pathway and ultimately disrupt the interaction with the LDL receptor, strategy for intracellular enzyme inhibition | Homo sapiens |
medicine | biologic-based strategies to inhibit proprotein convertase subtilisin/kexin type 9 show promise as anti-hypercholesterolemic and, therefore, anti-atherosclerotic therapies | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant His-tagged enzyme catalytic domain expression in HEK-293T cells and secretion to the medium | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | a secretion-defective PCSK9 mutant can transfer its prodomain to a prodomain-deficient (and also secretion-defective) enzyme, rescuing the secretion of the latter enzyme species | Homo sapiens |
Q152H | a dominant negative mutation that restricts enzyme proteolysis and secretion independently | Homo sapiens |
Q152I | te mutation completely abrogates proteolysis in both intra- and intermolecular systems but has only a limited impact on secretion | Homo sapiens |
Q152R | the mutation completely abolished both proteolysis and secretion | Homo sapiens |
Q152X | four phenotypes of Q152X mutants, overview | Homo sapiens |
S386A | inactive mutant | Homo sapiens |
V149A | the mutant shows intolerance for intermolecular cleavage of the enzyme, residue Val149 is critical for secretion | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
extracellular | the enzyme's prodomain inhibits intermolecular proteolysis in trans and requires the C-terminus for full inhibition and proper secretion, residue Val149 is critical for secretion | Homo sapiens | - |
- |
additional information | residues of the prodomain C-terminus regulate proteolysis and secretion independently | Homo sapiens | - |
- |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8NBP7 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | conversion of wild-type proPCSK9 to mature PCSK9 occurs in an intramolecular fashion, but the prodomain and catalytic domain can be assembled in trans (i.e. as two separate polypeptides), which effectively bypasses the need for proteolysis and does not require intrinsic proteolytic activity | Homo sapiens |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged enzyme from HEK-293T cell medium by nickel affinity chromatography | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | the enzyme catalytic domain is capable of proteolysis in trans (i.e. as two separate polypeptides), and can perform intermolecular proteolysis | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
PCSK9 | - |
Homo sapiens |
proprotein convertase subtilisin/kexin type 9 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
additional information | differential structural requirements of the proteolytic site and requirements for secretion in trans in a system that effectively bypasses the need for proteolysis, overview. The enzyme's prodomain inhibits intermolecular proteolysis in trans and requires the C-terminus for full inhibition and proper secretion. the enzyme's active site and its adjacent residues serve as an allosteric modulator of protein secretion independent of its role in proteolysis, specific residues in the protease recognition sequence can differentially modulate the effects on proteolysis and secretion | Homo sapiens |
physiological function | residues of the prodomain C-terminus regulate proteolysis and secretion independently. The prodomain C-terminus regulates protein secretion but is not required for catalytic domain binding | Homo sapiens |