EC Number   |
General Information |
Reference |
|---|
   3.4.21.61 | malfunction |
at t = 585 min, PCSK9-/- hepatocytes exhibit 90% less activity than wild-type |
707332 |
| 3.4.21.61 | malfunction |
cells with lower PCSK9 expression and secretion have a low density lipoprotein binding activity augmented by 200% |
707332 |
| 3.4.21.61 | malfunction |
D374Y is a naturally occurring gain-of-function mutation causing severe hypercholesterolaemia in humans due to a significantly decreased dissociation rate constant, whereas the mutation does not affect the association rate constant |
732857 |
| 3.4.21.61 | malfunction |
enzyme-knockout mice have more visceral adipose tissue. Enzyme-knockout mice carry more LDL receptor and less insulin in the pancreas, leading to hyperglycemia and glucose intolerance. beta-cell islets of enzyme-knockout mice inhibit signs of inflammation and apoptosis. This phenotype is modulated by gender and age |
731241 |
| 3.4.21.61 | malfunction |
gain-of-function mutations of the enzyme are associated with hypercholesterolemia and increased risk of cardiovascular events, while loss-of-function mutations cause low-plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. Mutations of the enzyme leading to reduced expression and or function are associated with a reduced rate of coronary heart disease, myocardial infarction and overall cardiovascular events, an effect being more pronounced in colored as compared to white subjects |
731241 |
| 3.4.21.61 | malfunction |
in addition to its effect on LDL-cholesterol, PCSK9 deficiency may protect against cardiovascular disease by reducing postprandial triglyceridemia: PCSK9-deficient mice show a dramatically decreased postprandial triglyceridemia compared with their wild-type littermates. Intestinal triglyceride output is not quantitatively modified by PCSK9 deletion. PCSK9-/- mice present with a significant reduction of lymphatic apoB secretion compared to PCSK9+/+ mice. PCSK9-/- mice secrete larger triglyceride-rich lipoprotein than wild-type littermates. PCSK9-deficient mice have an increased ability to clear chylomicrons compared to wild-type littermates. The dramatic reduction of postprandial lipemia in PCSK9-/- mice results from the combination of various effects, including the intestinal secretion of larger chylomicrons, and their higher hepatic clearance rate |
707305 |
| 3.4.21.61 | malfunction |
lack of PCSK6-dependent corin activation leads to hypertension. PCSK6-mediated processing of corin is reduced in the presence of corin variants T555I and Q568P previously associated to hypertension and to heart disease |
753290 |
| 3.4.21.61 | metabolism |
an interaction between the prodomain and C-terminal domain regulates the secretion of PCSK9 |
717860 |
| 3.4.21.61 | metabolism |
PCSK6 can activate NF-kappaB, STAT3 and ERK1/2 signaling pathways in vitro to enhance cell proliferation, migration, invasion and inflammation in rheumatoid arthritis synovial fibroblast (RASF) cells. Recombinant enzyme rhPCSK6 promotes the production of pro-inflammatory factors in RASFs. Pro?inflammatory cytokines serve promixadnent roles in rheumatoid arthritis. RASFs can secrete interleukin (IL)-1alpha, IL-1beta, IL-6, IL-17, and TNF-alpha |
754760 |
| 3.4.21.61 | more |
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 |
732152 |
