Structure of von Willebrand Factor-cleaving Protease (ADAMTS13), a Metalloprotease Involved in Thrombotic Thrombocytopenic Purpura*
By Xinglong Zheng, D. Chung, T. Takayama, Elaine M. Majerus, J. Sadler, K. Fujikawa. 2001
863 citations recorded by the source corpus.
Thrombotic thrombocytopenic purpura is associated with acquired or congenital deficiency of a plasma von Willebrand factor-cleaving protease (VWFCP). Based on partial amino acid sequence, VWFCP was identified recently as a new member of the ADAMTS family of metalloproteases and designated ADAMTS13. The 4.6-kilobase pair cDNA sequence for VWFCP has now been determined. By Northern blotting, full-length VWFCP mRNA was detected only in liver. VWFCP consists of 1427 amino acid residues and has a signal peptide, a short propeptide terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat, a Cys-rich domain, an ADAMTS spacer, seven additional thrombospondin-1 repeats, and two CUB domains. VWFCP apparently is made as a zymogen that requires proteolytic activation, possibly by furin intracellularly. Sites for Zn2+ and Ca2+ ions are conserved in the protease domain. The Cys-rich domain contains an RGDS sequence that could mediate integrin-dependent binding to platelets or other cells. Alternative splicing gives rise to at least seven potential variants that truncate the protein at different positions after the protease domain. Alternative splicing may have functional significance, producing proteins with distinct abilities to interact with cofactors, connective tissue, platelets, and von Willebrand factor.
Subfields: Hematology, Immunology
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Citations in the corpus
- Platelet-neutrophil-interactions: linking hemostasis and inflammation. (2007, background): “vWF secreted from endothelial cells is rich in ultra large (UL) multimers and is normally cleaved by a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) 13 into smaller and less active forms.(36,37) The disruption of the balance between vWF release and cleavage by ADAMTS 13 can lead”
- FRETS‐VWF73, a first fluorogenic substrate for ADAMTS13 assay (2005, background): “ADAMTS13 encodes a plasma metalloprotease of the ADAMTS family (Levy et al, 2001; Soejima et al, 2001; Zheng et al, 2001; Plaimauer et al, 2002; Banno et al, 2004).”
- Biochemistry and physiological functions of ADAMTS7 metalloprotease (2013, background): “ADAMTS7 acts as a negative regulator of endplate chondrocyte differentiation because it downregulates the expression of collagen type II, collagen type X, and Sox9 [44], which are early and late marker genes for chondrogenesis.”
- Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity (2006, background): “The MELD score was 10 [6-18] (median [range]) in the Child A group, 13 [7-23] in the Child B group, 18 [13-36] in the Child C group, and 28 [22-36] in the acute liver failure group.”