EC Number   |
Posttranslational Modification |
Reference |
|---|
   3.4.21.61 | glycoprotein |
mutation of N-glycosylation site N146 results in the decreased zymogen activation of proPC1/3 and virtually inhibits its secretion. Mutation of glycosylation site N618A mutation does not significantly affect zymogen activation. The presence, but not the exact structure, of N-glycans is crucial for proPC1/3 zymogen processing |
717642 |
| 3.4.21.61 | proteolytic modification |
autocatalytic processing of the single-chain enzyme precursor in the endoplasmic reticulum is required for enzyme activation. Ca2+-dependent enzyme-processing activities of hepsin and furin. Proprotein convertase furin cleaves the enzyme at Arg218-Gln219 in the surface-exposed 218 loop, furin cleavage sequence is 215RFHRQ219. The serine protease hepsin cleaves PCSK9 at the furin cleavage site. The furin-cleaved form circulates in blood along with the intact form, albeit at lower concentrations, and is no longer able to degrade LDL receptor attributed to the loss of the N-segment, as well as the prodomain from PCSK9. neutralizing anti-hepsin antibody Ab25 completely inhibits enzyme cleavage. Enzyme domains and protease cleavage sites, overview |
732078 |
| 3.4.21.61 | 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 |
732152 |
| 3.4.21.61 | proteolytic modification |
the pro-form of the enzyme is synthesized in the endoplasmic reticulum. The binding of pro-PCSK9 to the low-density lipoprotein receptor in the endoplasmic reticulum supports the transport of the low-density lipoprotein receptor towards the Golgi complex. Trafficking of the pro-enzyme to the Golgi apparatus depends on the presence of the protein Sec24A. Within the Golgi, the pro-domain of the pro-enzyme is autocatalytically cleaved off, but remains non-covalently bound to the mature enzyme assisting the folding of the enzyme, and blocking its catalytic activity. Binding of pro-enzyme to the precursor form of the low-density lipoprotein receptor promotes PCSK9 autocatalytic cleavage |
731241 |
