Protein Variants | Comment | Organism |
---|---|---|
F216L | a naturally occurring gain-of-function mutation associated with hypercholesterolemia, the mutation impairs furin-mediated enzyme cleavage | Homo sapiens |
R215H | a naturally occurring gain-of-function mutation associated with hypercholesterolemia, the mutation impairs furin-mediated enzyme cleavage | Homo sapiens |
R218S | a naturally occurring gain-of-function mutation associated with hypercholesterolemia, the mutation impairs furin-mediated enzyme cleavage | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | binding affinities/association and dissociation constants of LDL receptor interaction with intact and cleaved enzyme, overview | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
extracellular | - |
Homo sapiens | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
low density lipoprotein receptor-related protein 1 + H2O | Homo sapiens | degradation | ? | - |
? | |
additional information | Homo sapiens | both furinand hepsin-cleaved enzymes are able to degrade LDL receptor on HepG2 cells resulting in elevated serum cholesterol levels | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8NBP7 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
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 | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
blood plasma | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
low density lipoprotein receptor-related protein 1 + H2O | degradation | Homo sapiens | ? | - |
? | |
additional information | both furinand hepsin-cleaved enzymes are able to degrade LDL receptor on HepG2 cells resulting in elevated serum cholesterol levels | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
PCSK9 | - |
Homo sapiens |
proprotein convertase subtilisin/kexin type 9 | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
20 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | proprotein convertase subtilisin/kexin 9 regulates plasma LDL cholesterol levels by regulating the degradation of LDL receptors, furin resistance is the underlying molecular mechanism for the gain of function phenotype | Homo sapiens |