Defective F8 cleavage by thrombin

Stable Identifier
R-HSA-9672391
Type
Pathway
Species
Homo sapiens
Compartment
extracellular region
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective F8 cleavage by thrombin
Click the image above or here to open this pathway in the Pathway Browser
In normal human plasma, thrombin cleaves factor VIII (FVIII) after arginine residues 391 (A1-A2 domain junction) and 759 (A2-B domain junction) to yield heavy chain fragments and at R1708 (a3-A3 junction) to yield the light chain fragment (Eaton D et al. 1986; Hill-Eubanks DC et al. 1989). Mutations affecting arginine residues located at the thrombin cleavage sites of factor VIII protein result in mild/moderate hemophilia A (HA) (Pattinson JK et al. 1990; Arai M et al. 1990; Schwaab R et al. 1991). The Reactome event describes failed thrombin-mediated activation of HA-associated FVIII variants (R391C, R391H, S392L, R1708C and R1708H) due to defects at or close to thrombin cleavage sites.
Literature References
PubMed ID Title Journal Year
8052958 Factor VIII S373L: mutation at P1' site confers thrombin cleavage resistance, causing mild haemophilia A

O'Brien, DP, Tuddenham, EG, Pemberton, S, Acquila, M, Mori, PG, Johnson, DJ

Thromb. Haemost. 1994
1973901 CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy chain thrombin cleavage site

Tuddenham, EG, Boon, M, McVey, JH, Pattinson, JK, Ajani, A

Br. J. Haematol. 1990
19240027 Cleavage at Arg-1689 influences heavy chain cleavages during thrombin-catalyzed activation of factor VIII

Newell, JL, Fay, PJ

J. Biol. Chem. 2009
2109644 Purification and characterization of factor VIII 372-Cys: a hypofunctional cofactor from a patient with moderately severe hemophilia A

Tuddenham, EG, O'Brien, DP, Pattinson, JK

Blood 1990
15705787 Thrombin-catalyzed activation of factor VIII with His substituted for Arg372 at the P1 site

Zhou, Q, Fay, PJ, Wakabayashi, H, Nogami, K

Blood 2005
2104766 Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A

Antonarakis, SE, Janco, RL, Kazazian, HH, Higuchi, M, Hoyer, LW, Arai, M, Phillips, JA

Blood 1990
1851341 Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain

Ludwig, M, McVey, JH, Oldenburg, J, Kochhan, L, Schwaab, R, Brackmann, HH, Egli, H, Olek, K

Thromb. Res. 1991
Participants
Events
Participates
as an event of
Disease
Name Identifier Synonyms
factor VIII deficiency DOID:12134 Congenital factor VIII disorder, Subhemophilia, Hemophilia A
Cross References
BioModels Database
Authored
Shamovsky, V  (2019-09-09)
Reviewed
D'Eustachio, P  (2020-01-09)
Zhang, B  (2020-04-02)
Created
Shamovsky, V  (2019-12-25)
Cite Us!