Contents

Search

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)

Function: 1) Ca+2-binding protease cleaves the von Willebrand factor multimers (VWF) into fragments of 176 & 140 kD 2) cleavage occurs between Tyr-842 & Met-843 3) acts on vWF that has been unfolded by shear stress or other means 4) Zn+2 & Ca+2 cooperatively modulate enzyme activity 5) precursor is processed by a furin endopeptidase 6) 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. Cofactor: 1) binds 1 Zn+2 per subunit 2) binds 4 Ca+2 per subunit 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: secreted, plasma Expression: expressed primarily in liver Polymorphism: influence plasmatic ADAMTS13 activity Pathology: 1) defects in ADAMTS13 are associated with congenital thrombotic thrombocytopenic purpura (TTP) Pharmacology: - Adzynma is a recombinant ADAMTS13 FDA-approved to treat adult & pediatric patientswith congenital thrombotic thrombocytopenic purpura Laboratory: - von Willebrand factor-cleaving protease in plasma - vWF cleaving protease inhibitor in plasma

Related

von Willebrand factor (vWF)-cleaving protease (ADAMTS-13) in plasma

Specific

recombinant ADAMTS13-krhn

General

A disintegrin & metalloproteinase with thrombospondin type 1 motif (ADAMTS) Ca+2 binding protein

Properties

SIZE: entity length = 1427 aa MW = 154 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-29} Peptidase M12B {80-286} MOTIF: Ca+2-binding site SITE: 83-83 N-glycosylation site {N142} N-glycosylation site {N146} Ca+2-binding site SITE: 173-173 cysteine residue {C202} MODIFICATION: cysteine residue {C281} Zn+2-binding site SITE: 224-224 glutamate residue {E225} Zn+2-binding site SITE: 228-228 Zn+2-binding site SITE: 234-234 cysteine residue {C242} MODIFICATION: cysteine residue {C265} cysteine residue {C265} MODIFICATION: cysteine residue {C242} Ca+2-binding site SITE: 281-281 cysteine residue {C281} MODIFICATION: cysteine residue {C202} Ca+2-binding site SITE: 284-284 disintegrin domain {287-383} MOTIF: Cysteine-rich {300-374} TSP1 module {384-439} MOTIF: cysteine residue {C396} MODIFICATION: cysteine residue {C433} cysteine residue {C400} MODIFICATION: cysteine residue {C438} cysteine residue {C411} MODIFICATION: cysteine residue {C423} cysteine residue {C423} MODIFICATION: cysteine residue {C411} cysteine residue {C433} MODIFICATION: cysteine residue {C396} cysteine residue {C438} MODIFICATION: cysteine residue {C400} Cell attachment site {498-500} N-glycosylation site {N552} Spacer {556-685} MOTIF: N-glycosylation site {N579} N-glycosylation site {N614} N-glycosylation site {N667} TSP1 module {682-730} MOTIF: N-glycosylation site {N707} TSP1 module {742-805} TSP1 module {808-859} MOTIF: N-glycosylation site {N828} TSP1 module {896-950} TSP1 module {951-1011} TSP1 module {1012-1068} TSP1 module {1072-1131} CUB domain {1192-1298} MOTIF: N-glycosylation site {N1235} CUB domain {1299-1427} MOTIF: N-glycosylation site {N1354}

Database Correlations

OMIM correlations MORBIDMAP 604134 UniProt Q76LX8 PFAM correlations Entrez Gene 11093 Kegg hsa:11093

References

  1. 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: 9828245
  2. 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: 9828246
  3. 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: 8639781
  4. UniProt :accession Q76LX8
  5. Wikipedia; Note: ADAMTS13 entry http://en.wikipedia.org/wiki/ADAMTS13
  6. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADAMTS13
  7. SeattleSNPs http://pga.gs.washington.edu/data/adamts13/