Literature summary for 3.4.21.69 extracted from

Liang, H.P.; Kerschen, E.J.; Basu, S.; Hernandez, I.; Zogg, M.; Jia, S.; Hessner, M.J.; Toso, R.; Rezaie, A.R.; Fernandez, J.A.; Camire, R.M.; Ruf, W.; Griffin, J.H.; Weiler, H.
Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice (2015), Blood, 126, 2415-2423 .

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Protein Variants

Protein Variants	Comment	Organism
additional information	a signaling-selective 5A-aPC variant lacks deleterious effects upon early administration	Mus musculus
R506Q	site-directed mutagenesis, the Leiden mutation, abrogates the anti-inflammatory cofactor function of factor V for activated protein C	Mus musculus

Inhibitors

Inhibitors	Comment	Organism	Structure
coagulation factor V	fV, mediates inhibition of inflammatory tissue factor signaling by enzyme aPC	Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
pro-factor V + H2O	Mus musculus	cleavage at R506	factor V + ?	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	P33587	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
bone marrow	-	Mus musculus	-
bone marrow-derived dendritic cell	-	Mus musculus	-
monocyte	-	Mus musculus	-
RAW-264.7 cell	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
pro-factor V + H2O	cleavage at R506	Mus musculus	factor V + ?	-	?
pro-factor VIIa + H2O	recombinant substrate	Mus musculus	factor VIIa + ?	-	?

Synonyms

Synonyms	Comment	Organism
Activated protein C	-	Mus musculus
APC	-	Mus musculus

Cofactor

Cofactor	Comment	Organism	Structure
protein S	-	Mus musculus

General Information

General Information	Comment	Organism
malfunction	coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice. aPC resistance of factor (f)V due to the R506Q Leiden mutation protects against detrimental anticoagulant effects of aPC therapy but also abrogates the anti-inflammatory and mortality reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. aPC resistance of fV Leiden suppresses in vitro regulation of inflammatory gene expression by aPC, overview	Mus musculus
metabolism	activated protein C is the key effector molecule of the natural protein C pathway. Biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of factor V are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection, overview	Mus musculus
physiological function	coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. Using a mouse model of Staphylococcus aureus sepsis,marked disease stage-specific effects of the anticoagulant and cell signaling functions of aPC are demonstrated. Factor V and protein S are required for sepsis mortality reduction and suppression of inflammatory gene expression by activated protein C. Procofactor V (cleaved by aPC at R506) and protein S are necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The antiinflammatory cofactor function of fV involves the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities do not involve proteolysis of activated coagulation factors Va and VIIIa. Sepsis stage-related response to infusion of aPC variants, overview. Inhibition of tissue factor-EPCR-PAR2 signaling by enzyme aPC requires protein S and the factor V B domain. aPC inhibits PAR2 activation by the ternary tissue factor-factor VIIa-factor Xa complex	Mus musculus

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Release 2023.1 (January 2023)