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Literature summary for 3.4.21.61 extracted from

  • Du, F.; Hui, Y.; Zhang, M.; Linton, M.; Fazio, S.; Fan, D.
    A novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (2011), J. Biol. Chem., 286, 43054-43061.
    View publication on PubMedView publication on EuropePMC
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Application

Application Comment Organism
medicine a discrete C-terminal protein fragment competes with full-length PCSK9 for binding to LDLR in vitro and attenuates PCSK9-mediated hypercholesterolemia in mice Mus musculus

Cloned(Commentary)

Cloned (Comment) Organism
expression in HEK293T and HepG2 cells Mus musculus
expression in HEK293T and HepG2 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information deletion of prodomain residues 31-40, 41-50, or 51-60 does not affect the self-cleavage, secretion, or LDLR-degrading activity of PCSK9, whereas deletion of residues 61-70 abolishes all of these functions. Deletion of the entire C-terminal domain does not impair PCSK9 self-cleavage or secretion but completely abolishes LDLR-degrading activity. Deletion of any one or two of the C-terminal domain modules does not affect self-cleavage but influences secretion and LDLR-reducing activity. In cotransfection experiments, a secretion-defective prodomain deletion mutant is efficiently secreted in the presence of C-terminal domain deletion mutants due to the transfer of the prodomain from the cotransfected C-terminal domain mutant to the prodomain mutant Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
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Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
low density lipoprotein receptor + H2O a discrete C-terminal protein fragment competes with full-length PCSK9 for binding to LDLR in vitro and attenuates PCSK9-mediated hypercholesterolemia in mice Mus musculus ?
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low density lipoprotein receptor + H2O C-terminal domain of enzyme has a stronger affinity for substrate low density lipoprotein receptor than catalytic domain. A C-terminal deletion mutant does not mediate low density lipoprotein receptor degradation Homo sapiens ?
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 ?

General Information

General Information Comment Organism
metabolism an interaction between the prodomain and C-terminal domain regulates the secretion of PCSK9 Homo sapiens