A disintegrin & metalloproteinase with thrombospondin type 1 motif 13; ADAMTS-13; ADAM-TS 13; ADAM-TS13; von Willebrand factor-cleaving protease; vWF-cleaving protease; vWF-CP (ADAMTS13, C9orf8, UNQ6102/PRO20085)
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Function
- Ca+2-binding protease cleaves the von Willebrand factor multimers (VWF) into fragments of 176 & 140 kD
- cleavage occurs between Tyr-842 & Met-843
- acts on vWF that has been unfolded by shear stress or other means
- Zn+2 & Ca+2 cooperatively modulate enzyme activity
- precursor is processed by a furin endopeptidase
- protease activity requires divalent a metal cation; activation by divalent metal cation increases in the order: Zn+2 = Cu+2 = Cd+2 = Ni+2 = Co+2 < Mn+2 < Mg+2 < Ca+2 < Sr+2 < Ba+2.
Structure
- pro-domain is not required for folding or secretion & does not perform common function of maintaining enzyme latency
- spacer domain is necessary to recognize & cleave vWF
- C-terminal TSP type-1 & CUB domains may modulate this interaction
- contains 2 CUB domains
- contains 1 disintegrin domain
- contains 1 peptidase M12B domain
- contains 8 TSP type-1 domains
Compartment
Expression
expressed primarily in liver
Pathology
- defects in ADAMTS13 are associated with congenital thrombotic thrombocytopenic purpura (TTP)
Polymorphism
influence plasmatic ADAMTS13 activity
Pharmacology
- Adzynma is a recombinant ADAMTS13 FDA-approved to treat adult & pediatric patientswith congenital thrombotic thrombocytopenic purpura
Laboratory
More general terms
More specific terms
References
- ↑ Furlan M et al von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998 Nov 26;339(22):1578-84. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9828245
- ↑ Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998 Nov 26;339(22):1585-94. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9828246
- ↑ Furlan M et al Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996 May 15;87(10):4223-34. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8639781
- ↑ UniProt http://www.uniprot.org/uniprot/Q76LX8.html
- ↑ Wikipedia; Note: ADAMTS13 entry http://en.wikipedia.org/wiki/ADAMTS13
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADAMTS13
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/adamts13/
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=11093
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:11093
- OMIM: https://mirror.omim.org/entry/235400
- OMIM: https://mirror.omim.org/entry/274150
- OMIM: https://mirror.omim.org/entry/604134
- UniProt: http://www.uniprot.org/uniprot/Q76LX8.html