Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.21.61 extracted from

  • Lipari, M.T.; Li, W.; Moran, P.; Kong-Beltran, M.; Sai, T.; Lai, J.; Lin, S.J.; Kolumam, G.; Zavala-Solorio, J.; Izrael-Tomasevic, A.; Arnott, D.; Wang, J.; Peterson, A.S.; Kirchhofer, D.
    Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels (2012), J. Biol. Chem., 287, 43482-43491.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.21.61

Protein Variants

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 [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

Localization Comment Organism GeneOntology No. Textmining
extracellular
-
 Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens Q8NBP7
-
-

Posttranslational Modification

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

Source Tissue Comment Organism Textmining
blood plasma
-
 Homo sapiens
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
PCSK9
-
 Homo sapiens
proprotein convertase subtilisin/kexin type 9
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
20
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Homo sapiens

General Information

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