Enhanced cleavage of VWF variant by ADAMTS13

Stable Identifier
R-HSA-9845619
Type
Pathway
Species
Homo sapiens
Compartment
extracellular region
ReviewStatus
5/5
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Enhanced cleavage of VWF variant by ADAMTS13
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Under normal physiological conditions, a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) downregulates von Willebrand factor (VWF) procoagulant activity by cleaving the peptide bond between Tyr1605 and Met1606 of VWF in a shear-dependent manner. This Reactome event describes von Willebrand disease (VWD)-associated missense mutations VWF Y1584C (Bowen DJ et al., 2005; Keeney S et al., 2007; Pruss CM et al., 2012), I1568N, G1579R, G1631D, and C1099P (Jacobi PM et al., 2012), which showed enhanced susceptibility to ADAMTS13-mediated proteolysis.
Literature References
PubMed ID Title Journal Year
21346256 Pathologic mechanisms of type 1 VWD mutations R1205H and Y1584C through in vitro and in vivo mouse models

Sponagle, K, Golder, M, Haberichter, S, Notley, C, Bryant, A, Dhala, A, Laverty, K, Burnett, E, Lillicrap, D, Hegadorn, CA, Pruss, CM

Blood 2011
22431572 Intersection of mechanisms of type 2A VWD through defects in VWF multimerization, secretion, ADAMTS-13 susceptibility, and regulated storage

Jacobi, PM, Gill, JC, Haberichter, SL, Flood, VH, Jakab, DA, Friedman, KD

Blood 2012
15755288 The prevalence of the cysteine1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype

Cumming, AM, Enayat, SM, Bowen, DJ, Keeney, S, Hill, FG, Grundy, P, Pasi, KJ, Wilde, JT, Khair, K, Tait, RC, UK Haemophilia Centre Doctors' Organization, -, Keeling, DM, Lester, W, Bolton-Maggs, PH, Collins, PW

Br J Haematol 2005
16322474 Impact of mutations in the von Willebrand factor A2 domain on ADAMTS13-dependent proteolysis

Budde, U, Obser, T, Hassenpflug, WA, Drewke, E, Angerhaus, D, Schneppenheim, S, Schneppenheim, R

Blood 2006
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Events
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Disease
Name Identifier Synonyms
blood platelet disease DOID:2218 platelet disorder, Thrombocytopathy
Authored
Shamovsky, V  (2023-01-07)
Reviewed
Gao, R  (2023-11-06)
Created
Shamovsky, V  (2023-10-06)
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