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Literature summary for 3.4.21.69 extracted from

  • Bae, J.S.; Yang, L.; Manithody, C.; Rezaie, A.R.
    Engineering a disulfide bond to stabilize the calcium-binding loop of activated protein C eliminates its anticoagulant but not its protective signaling properties (2007), J. Biol. Chem., 282, 9251-9259.
    View publication on PubMed

Application

Application Comment Organism
medicine the activated protein C exhibits anti-inflammatory and cytoprotective properties, which may contribute to the beneficial effect of APC in treating severe sepsis patients, a higher incidence of bleeding because of its anticoagulant function is a major drawback of APC as an effective anti-inflammatory drug Homo sapiens

Protein Variants

Protein Variants Comment Organism
R67C/R82C site-directed mutagenesis, construction of a protein C variant in which an engineered disulfide bond between two beta-sheets stabilizes the functionally critical Ca2+-binding 70-80 loop of the molecule. The 70-80 loop of this mutant no longer binds Ca2+, and the activation of the mutant by thrombin is enhanced 60-80fold independently of thrombomodulin, the anticoagulant activity of the activated protein C mutant is nearly eliminated. The endothelial protein C receptor- and protease activated receptor-1-dependent protective signaling properties of the mutant are minimally altered compared to the wild-type enzyme. The mutant loses its ability to interact with the procoagulant cofactors but not with the protective signaling molecules. The binding of EPCR is 2fold reduced compared to the wild-type enzyme Homo sapiens
S195A site-directed mutagenesis, inactive mutant Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular activated protein C Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ required, calcium enhances the amidolytic activity of APC by 2fold, the Ca2+ and Na+ metal ion-binding sites are linked energetically Homo sapiens
Na+ the amidolytic activity of APC is strictly dependent on Na+, the Ca2+ and Na+ metal ion-binding sites are linked energetically Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
active factor Va + H2O Homo sapiens proteolytic inactivation requires interactions with both EPCR and PAR-1 inactive factor V + domain B
-
?
additional information Homo sapiens in addition to an anticoagulant activity, activated protein C also exhibits anti-inflammatory and cytoprotective properties, but can cause bleeding because of its anticoagulant function, the cytoprotective activity of APC is mediated through inhibition of caspase-3 activity ?
-
?
protease activated receptor 1 + H2O Homo sapiens activation ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein different variants Homo sapiens
proteolytic modification the protein C zymogen is activate through cleavage by thrombin in a Ca2+-dependent manner, thrombin acts in complex with the required thrombomodulin, the reaction is is markedly stimulated by endothelial protein C receptor Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
plasma activated protein C Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
active factor Va + H2O proteolytic inactivation requires interactions with both EPCR and PAR-1 Homo sapiens inactive factor V + domain B
-
?
additional information in addition to an anticoagulant activity, activated protein C also exhibits anti-inflammatory and cytoprotective properties, but can cause bleeding because of its anticoagulant function, the cytoprotective activity of APC is mediated through inhibition of caspase-3 activity Homo sapiens ?
-
?
protease activated receptor 1 + H2O activation Homo sapiens ?
-
?
protease activated receptor 1 + H2O activation, cleavage at Arg41 Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
Activated protein C
-
Homo sapiens
APC
-
Homo sapiens