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Information on EC 3.4.24.87 - ADAMTS13 endopeptidase
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3.4.24.87 ADAMTS13 endopeptidaseSpecify your search results
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- 3.4.24.87
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thrombotic
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thrombocytopenic
- purpura
- ttp
- platelet
- multimers
-
hemolytic
- anemia
- endothelial
- metalloproteinase
- autoantibody
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microangiopathic
- rituximab
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remission
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uremic
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microvascular
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relapse
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life-threatening
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shear
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idiopathic
- coagulation
- autoimmune
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thrombi
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bleeding
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hemostasis
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schistocytes
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intravascular
-
relapsing
-
plasmapheresis
-
ultra-large
-
hemostat
-
disintegrin-like
-
microcirculation
-
vwf:ag
-
coombs
- plasmic
-
microthrombi
-
shiga
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hellp
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collagen-binding
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antiphospholipid
-
microthrombosis
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d-dimers
- fviii
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prothrombotic
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apheresis
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hemolytic-uremic
- ristocetin
- eculizumab
- medicine
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oklahoma
- analysis
- drug development
- diagnostics
The enzyme appears in viruses and cellular organisms
Reaction Schemes
The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
Synonyms
adamts13, adamts-13, von willebrand factor-cleaving protease, vwf-cp, vwf-cleaving protease, adamts 13, von willebrand factor cleaving protease, vwf cleaving protease, metalloprotease adamts-13, vwf protease, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
a disintegrin and metalloprotease with thrombospondin motifs 13
a disintegrin and metalloprotease with thrombospondin type 1 repeats 13
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a disintegrin and metalloproteinase with a thrombonspondin type 1 motif member 13
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a disintegrin and metalloproteinase with a thrombospondin motif repeats 13
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a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
a disintegrin-like and metalloprotease with thrombospondin type I repeats 13
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a disintegrin-like and metalloproteinase domain with thrombospondin type I motifs 13
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a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13
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a disintegrin-like domain and metalloprotease with thrombospondin type I motif
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ADAMTS-13
ADAMTS13
M12.241
plasma metalloprotease ADAMTS13
von Willebrand cleavage protease
von Willebrand factor-cleaving protease
vWF-cleaving protease
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-
additional information
a disintegrin and metalloprotease with thrombospondin motifs 13
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a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
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a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
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ADAMTS-13
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ADAMTS-13
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i.e. a disintegrin and metalloprotease with a thrombospondin type 1 motifs 13
ADAMTS13
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650710, 652431, 653678, 668071, 669457, 669524, 670936, 677437, 678918, 678919, 678964, 678966, 679396, 680056, 680535, 680929, 682525, 682901, 682939, 710826, 710827, 711086, 711560, 711564, 711565, 711566, 711571, 711572, 711574, 711575, 711579, 712099, 712115, 712127, 712195, 712393, 712568, 712569, 712570, 712899, 713189, 713347, 713381, 713531, 713533, 713536, 713560, 713561, 713562, 719160, 719162, 719163, 719761, 719881, 720367, 720833, 753897, 754157, 754522, 755583, 755614
ADAMTS13
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ADAMTS13 belongs to the ADAMTS or a disintegrin-like and metalloproteinase with thrombospondin type-1 motif family
ADAMTS13
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ADAMTS13 is a member of the a disintegrin and metalloprotease with thrombospondin type 1 repeats, i.e. ADAMTS, family
ADAMTS13
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i.e. a disintegrin and metalloprotease with thrombospondin repeats
ADAMTS13
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i.e. a disintegrin-like and metalloprotease with trombospondin type-1 repeats 13
ADAMTS13
-
i.e. disintegrin-like domain and Metalloprotease with ThromboSpondin type I motif 13
ADAMTS13
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ADAMTS13
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i.e. a disintegrin-like and metalloprotease with trombospondin type-1 repeats 13
M12.241
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Merops-ID
von Willebrand factor-cleaving protease
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-
additional information
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a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13
additional information
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a disintegrin and metalloprotease with trombonspondin motif 13
additional information
-
ADAMTS13 belongs to the family of a disintegrin-like and metalloprotease domains with repeated thrombospondin domains
additional information
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ADAMTS13 is a member of a disintegrin and metalloprotease with thrombospondin type 1 repeats, ADAMTS, family
additional information
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ADAMTS13 is a member of the ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs, family of proteins
additional information
ADAMTS13 is a reprolysin-type metalloproteinase belonging to the ADAMTS, i.e. a disintegrin and metalloproteinase with thrombospondin type 1 motif, family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
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The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
active site sequence HEIGHSFGLEHE 150 amino acid residues from the N-terminus of the protein
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The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
active site sequence HEXXHXXGXXHD
The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
enzyme is a hemostatic factor
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The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
the cysteine-rich/spacer domains are essential for the proteolytic activity
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The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain
the spacer region is essential, while the C-terminal thrombospondin type 1 motif and the CUB domain are dispensable in vitro
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
334869-10-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
DREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRA + H2O
?
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i.e. VWF74 peptide, a pseudo-wild-type peptide von Willebrand factor 74, VWF74, encompassing the von Willebrand factor, VWF, A2 domain sequence 1596-1669
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-
?
fluorescence resonance energy transfer substrate-von Willebrand factor 73 + H2O
?
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?
fluorescent resonance energy transfer-von Willebrand factor 73 + H2O
?
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?
FRET-VWF115 peptide + H2O
?
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von Willebrand factor-derived peptide substrate comprising residues 1554-1668
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?
FRET-VWF73 + H2O
?
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fluorogenic von Willebrand factor-derived peptide substrate. The distal C-terminal domains of ADAMTS13 are not necessary for the cleavage of the VWF73-based peptide substrate
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?
FRETS-rVWF71 + H2O
?
substrate based on von Willebrand factor residues Gln1599-Arg1668, with an N-terminal Gly and with mutations N1610C and K1617R. The N-terminus is modified with IRDye QC-1 Nhydroxysuccinimide ester, and Cys1610 is modified with DyLight 633 maleimide
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?
FRETS-vWF73 + H2O
?
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a fluorogenic von Willebrand factor-derived peptide substrate
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-
?
FRETS-VWF73 peptide + H2O
?
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fluorogenic von Willebrand factor-derived peptide substrate
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?
FRETSVWF73 + H2O
?
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a von Willebrand factor-derived fluorescein-labeled peptide substrate
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?
FRETSVWF73 peptide + H2O
?
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a von Willebrand factor-derived fluorescein-labeled peptide substrate
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?
GST-von Willebrand factor 73 + H2O
?
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contains residues Asp1596-Arg1668 from von Willebrand factor domain A2
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-
?
HRPH-A2-B
?
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HRPH-A2-B is a derivative of von Willebrand factor 73, consisting of a HRP conjugate of a biotinylated von Willebrand factor 78 sequence
cleavage of Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
-
?
von Willebrand factor + H2O
2 peptides of 140 kD and 65 kD
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cleavage of peptide bond Tyr842-Met843
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?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
von Willebrand factor 115 + H2O
10000 Da fragment of von Willebrand factor 115 + 7000 Da fragment of von Willebrand factor 115
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von Willebrand factor is cleaved at the Tyr1605-Met1606 bond in the von Willebrand factor A2 domain
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?
von Willebrand factor 73 + H2O
?
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minimal substrate cleavable by ADAMTS-13
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?
VWF115 + H2O
10 kDa VWF115 fragment + 7 kDa VWF115 fragment
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VWFA2 domain fragment, spanning von Willebrand factor residues 1554-1668, generation of 2 cleavage products of 10 kDa and 7 kDa
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-
?
VWF115 D1614A mutant + H2O
10 kDa VWF115 fragment + 7 kDa VWF115 fragment
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Asp1614 VWFA2 domain fragment, spanning von Willebrand factor residues 1554-1668, generation of 2 cleavage products of 10 kDa and 7 kDa
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?
VWF73 region of von Willebrand factor + H2O
?
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with this minimal substrate urea is not required for cleavage, minimal substrate for ADAMTS-13
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?
VWFA2 peptide + H2O
?
substrate based on a 78-amino acid sequence corresponding to the sequence Leu1591-Arg1668 of the von Willebrand factor A2 domain
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?
VWFA2 peptide + H2O
VWFA2 peptide fragments
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A2 domain fragment of von Willebrand factor, cleavage of oxidized or nonoxidized VWFA2 peptide by ADAMTS13, cleavage of the Tyr1605-Met(O)1606 peptide bond by ADAMTS13, overview
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?
GST-VWF73 + H2O
?
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labeled von Willebrand factor-derived peptide substrate
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?
GST-VWF73 + H2O
?
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labeled von Willebrand factor-derived peptide substrate. The distal C-terminal domains of ADAMTS13 are not necessary for the cleavage of the VWF73-based peptide substrate
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?
proteins + H2O
peptides
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enzyme is involved in thrombotic thrombocytopenic purpura
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?
proteins + H2O
peptides
enzyme is involved in thrombotic thrombocytopenic purpura
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?
von Willebrand factor + H2O
2 peptides
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cleavage of peptide bond Tyr842-Met843
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?
von Willebrand factor + H2O
2 peptides
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cleavage site is located in the A2 domain of the substrate, cleavage of peptide bond Tyr842-Met843
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?
von Willebrand factor + H2O
2 peptides
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large multimeric complexes are reduced to smaller ones, cleavage of peptide bond Tyr842-Met843
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?
von Willebrand factor + H2O
2 peptides
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rapid physiological process that occurs on endothelial surfaces, reduced activity results in thrombotic thrombocytopenic pupura
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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ADAMTS13 cleaves von Willebrand factor at the Y1605/M1606 peptide bond in the A2 domain. Mutant substrates L1603Q, L1603R, Y1605D, L1603R/Y1605N, Y1605N/M1606T, Y1605R/M1606T are resistant to cleavage. Mutant substrates R1597W, M1606T and I1616N are less efficiently cleaved than wild-type
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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cleavage of the peptide bond Tyr842-Met843 within the A2 domain
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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cleavage of the peptide bond Tyr842-Met843 within the A2 domain
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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cleavage of the peptide bond Tyr842-Met843 within the A2 domain
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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specific cleavage of the peptide bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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cleavage of the peptide bond Tyr842-Met843 within the A2 domain, enzyme deficiency causes lethal thrombotic thrombocytopenic purpura
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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either congenital or acquired defects of the enzyme lead to thrombotic thromcytopenic purpura, cleavage of the peptide bond bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
-
?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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large multimeric substrate, cleavage of the peptide bond Tyr842-Met843 within the A2 domain
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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protein from plasma of patients suffering type I von Willebrand disease is more susceptible to proteolysis by the enzyme due to amino acid polymorphism heterozygous at position Tyr/Cys1584, phenotypic parameters, cleavage of the peptide bond Tyr842-Met843 within the A2 domain
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?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
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complete proteolysis is observed at 37°C in the presence of BaCl2 while about 25% von Willebrand factor still binds to collagen when BaCl2 supplementation is omitted. Proteolysis kinetics at 22°C and 4°C is slower but complete
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?
von Willebrand factor + H2O
2 peptides of 176 kD and 140 kD
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large multimeric complexes are reduced to smaller ones, cleavage of peptide bond Tyr842-Met843 in the vWFdomain A2
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?
von Willebrand factor + H2O
2 peptides of 176 kD and 140 kD
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large multimeric complexes are reduced to smaller ones, cleavage of peptide bond Tyr842-Met843 in the vWFdomain A2
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?
von Willebrand factor + H2O
2 peptides of 176 kD and 140 kD
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rapid physiological process that occurs on endothelial surfaces, activity is reduced by 87-100% in patients with thrombotic thrombocytopenic pupura
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?
von Willebrand factor + H2O
?
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669524, 677437, 678918, 678964, 679396, 680535, 680695, 681661, 681662, 681663, 682523, 682525, 682898, 682901, 682939, 710826, 710827, 711086, 711559, 711564, 711565, 711569, 711571, 711572, 711575, 711576, 711809, 712568, 713079, 713189, 713533, 713534, 713536, 719881, 720367, 720833, 753897, 754157, 754522, 755583
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?
von Willebrand factor + H2O
?
cleavage of peptide bond Tyr842-Met843, native and recombinant enzyme
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?
von Willebrand factor + H2O
?
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cleavage of peptide bond Tyr842-Met843, large hemostatically active multimers are cleaved to smaller less active forms, increased proteolytic degradation in patients suffering from von Willebrand disease typ 2A
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?
von Willebrand factor + H2O
?
cleavage of peptide bond Tyr842-Met843, rapid degradation of multimers to smaller fragments, decreased activity results in bone marrow transplant-associated thrombotic microangiopathy and thrombotic thrombocytopenic pupura
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?
von Willebrand factor + H2O
?
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decrease of the multimeric pattern of enzyme and decreased activity results in bone marrow transplant-associated thrombotid microangiopathy
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?
von Willebrand factor + H2O
?
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enzyme deficiency causes lethal thrombotic thrombocytopenic purpura, cleavage of peptide bond Tyr1605-Met1606 resulting in limited platelet accumulation in microvascular thrombi (Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275)
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?
von Willebrand factor + H2O
?
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the cleavage site is exposed to the enzyme by conformational changes due to shear stress in the plasma, decrease of the multimeric pattern of enzyme and decreased activity results in bone marrow transplant-associated thrombotic microangiopathy, cleavage of peptide bond Tyr842-Met843, large hemostatically active multimers are cleaved to smaller less active forms, increased proteolytic degradation in patients suffering von Willebrand disease typ 2A
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?
von Willebrand factor + H2O
?
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cleavage of Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
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?
von Willebrand factor + H2O
?
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important role for Asp1614 and surrounding charged residues in the binding and cleavage of the von Willebrand factor A2 domain
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?
von Willebrand factor + H2O
?
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VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13
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?
von Willebrand factor + H2O
?
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ADAMTS13 cleaves at the peptide bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
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?
von Willebrand factor + H2O
?
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ADAMTS13 cleaves the bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
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?
von Willebrand factor + H2O
?
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amino acid position C1584 is necessary for enhanced von Willebrand factor proteolysis by ADAMTS13
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?
von Willebrand factor + H2O
?
ADAMTS13 efficiently cleaves only the Tyr842-Met843 bond within the central A2 domain of multimeric von Willebrand factor (i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275)
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?
von Willebrand factor + H2O
?
ADAMTS13 efficiently cleaves only the Tyr842-Met843 bond within the central A2 domain of multimeric von Willebrand factor (i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275). This specificity depends in part on binding of the noncatalytic ADAMTS13 spacer domain to the C-terminal alpha-helix of von Willebrand factor domain A2. By kinetic analysis of recombinant ADAMTS13 constructs, it is shown that the first thrombospondin-1, Cys-rich, and spacer domains of ADAMTS13 interact with segments of von Willebrand factor domain A2 between Gln1624 and Arg1668 (in von Willebrand factor UniProt Id P04275), and together these exosite interactions increase the rate of substrate cleavage by at least approximately 300fold. Specific recognition of von Willebrand factor depends on cooperative, modular contacts between several ADAMTS13 domains and discrete segments of von Willebrand factor domain A2. Specification of the cleavage site depends on sequences flanking the scissile bond between positions P9 (Arg1597) and P18' (Ile1623)
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?
von Willebrand factor + H2O
?
all alterations examined in the Y1605-M1606 cleavage site greatly reduce the cleavability of von Willebrand factor by ADAMTS13. Greatest cleavage resistance is observed in Y1605A/M1606A. Y1605H and M1606L show a loss of cleavability in the recombinant full-length von Willebrand factor assay, suggesting that an aromatic ring at 1605 is critical for ADAMTS13 recognition. The G1643S polymorphism shows increased cleavage, suggesting a type 2A von Willebrand factor phenotype, while D1472H, Q1571H and P1601T show slightly decreased ADAMTS13 cleavage. A-domain changes in von Willebrand factor alter ADAMTS13-mediated proteolysis
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?
von Willebrand factor + H2O
?
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a catalysis-deficient ADAMTS13 P475S mutant does not show VWF-induced changes in conformation
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?
von Willebrand factor + H2O
?
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ADAMTS13 cleaves ultra-large von Willebrand factor multimers
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-
?
von Willebrand factor + H2O
?
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force-induced von Willebrand factor A2 domain unfolding of the substrate facilitates cleavage, using single VWF A1A2A3 tridomain polypeptides, structural destabilization of A1A2A3 was induced by 5- to 80-pN forces
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?
von Willebrand factor + H2O
?
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persistently elevated levels of von Willebrand factor in plasma during and after liver transplantation, while plasma levels of ADAMTS13 dropp during transplantation
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-
?
von Willebrand factor + H2O
?
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specific cleavage of ultra-large von Willebrand factor multimers
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-
?
von Willebrand factor + H2O
?
-
cleaving of ultra-large multimers between residues Tyr842 and Met843 in the central A2 domain, the TSP-1 domain of ADAMTS13 is required for interaction with the extracellular matrix and the substrate, as well as the CUB domains, that are also essential for intracellular trafficking
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-
?
von Willebrand factor + H2O
?
-
i.e. VWF, a large glycoprotein secreted by vascular endothelial cells as multimers
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?
von Willebrand factor + H2O
?
-
identification of ADAMTS13 peptide sequences binding to von Willebrand factor, overview
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-
?
von Willebrand factor + H2O
?
-
recombinant substrate stably expressed in HEK293 cells, the ADAMTS13 metalloprotease domain cleaves the von Willebrand factor A2 domain at the Y1605-M1606 scissile bond
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-
?
von Willebrand factor + H2O
?
-
the S119-W262 H-bond in the ADAMTS13 metalloprotease domain is crucial for maximal turnover
-
-
?
von Willebrand factor + H2O
?
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wild-type plasma-derived substrate of human origin, and substrate modified by alpha2-3,6,8,9-neuraminidase from Arthrobacter ureafaciens removing alpha2-3- and alpha2-6-linked sialic acid, and treatment with PNGase F to remove complex N-linked glycan structures. alpha2-6-linked sialic acid increases von Willebrand factor proteolysis by ADAMTS13 through a conformational mechanism, overview
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-
?
von Willebrand factor + H2O
?
-
ADAMTS-13 has thiol reductase activity limited towards von Willebrand factor
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?
von Willebrand factor + H2O
?
-
ADAMTS13 specifically cleaves von Willbrand factor A2 domain between Tyr1605 and Met1606
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-
?
von Willebrand factor + H2O
?
-
cleavage occurs at strand beta4 (Tyr1605-Met1606) in the structural core of the A2 domain. Ca2+ binding stabilizes the A2 domain and impedes its unfolding, and consequently protects it from cleavage by ADAMTS13
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-
?
von Willebrand factor + H2O
?
-
the disulfide-bond-reducing activity of ADAMTS-13 prevents covalent lateral association and increased platelet adherence of plasma-type von Willebrand factor multimers induced by high fluid shear stress
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-
?
von Willebrand factor + H2O
?
-
von Willebrand factor A2 domain unfolding is required for proteolysis by ADAMTS13, the ADAMTS13 cleavage site is at Tyr1605-Met1606
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-
?
von Willebrand factor + H2O
?
-
-
-
-
?
von Willebrand factor + H2O
?
-
specific cleavage of ultra-large von Willebrand factor multimers
-
-
?
von Willebrand factor + H2O
?
-
von Willebrand factor is also susceptible to cleavage by ADAMTS13 when incorporated in a thrombus
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. Very low activity with recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. The guinea pig ADAMTS13 shows no activity with the recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
-
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleavage of von Willebrand factor strings secreted from stimulated and unstimulated HUVECs occurs at the position 1605-6 of the von Willebrand factor A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleaves the Tyr1605-Met1606 bond in the VWF A2 domain, mechanisms of VWF recognition, cleavage analysis and kinetics under static and flow conditions, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleaves von Willebrand factor (VWF) exclusively at the Tyr1605-Met1606 peptide bond in the A2 domain
LC-MS product identification
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleavage of HUVEC-secreted von Willebrand factor strings at Y1605-6M sites of the von Willebrand factor A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleaves the Tyr1605-Met1606 bond in the VWF A2 domain, mechanisms of VWF recognition. One ADAMTS13 binding site of VWF is located in the region of VWF spanning residues 1874 to 2813, which includes the VWF D4 domain, interacts with the C-terminal domains of ADAMTS13, interaction occurs even when VWF is in static conditions, globular and with the VWF A2 domain hidden. The binding site may participate as the initial step of a multistep interaction ultimately leading to proteolysis of VWF byADAMTS13
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. Comparison of the activity with human recombinan substrate in vitro with enzymes from other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
binding of all the proximal noncatalytic domains of ADAMTS13 to von Willebrand factor is necessary to position the active site of ADAMTS13 to the scissile bond, Tyr1605-Met1606, on von Willebrand factor, resulting in productive cleavage. The metalloprotease domain of ADAMTS13 alone is ineffective in cleaving von Willebrand factor, linear relationship between the domains of ADAMTS13 and von Willebrand factor proteolysis. All the proximal noncatalytic domains of ADAMTS13 are required for productive engagement with von Willebrand factor-A2 domain at least under static/denaturing conditions
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. Activity with the recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. The wild-type mouse ADAMTS13 shows no activity with the recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. The rabbit ADAMTS13 shows activity similar to the human ADAMTS13 with the recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. The rat ADAMTS13 shows no activity with the recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain. Very low activity with recombinant human substrate in vitro, comparison to other mammal enzymes, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
-
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor to smaller less-active forms
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 specifically cleaves von Willebrand factor multimers at the site of the Tyr1605-Met1606 bond of the VWF-A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage at the Tyr1605-Met1606 bond within the van Willebrand factor A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage can also occur at the surface of endothelial cells. ADAMTS13 that is prebound to endothelial cells exhibits increased proteolysis of VWF as compared with ADAMTS13 present only in solution. Thus, cleavage of VWF occurs mainly at the endothelial cell surface
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage of ultra large von Willebrand multimers into smaller fragments
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
specific cleavage of the long strings of ultra-large von Willebrand factor multimers
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond. The ADAMTS13 spacer domain is required for cleavage of von Willebrand factor, role of the amino acid residues Arg659, Arg660, and Tyr661 of theADAMTS13 spacer domain in substrate recognition, sequence comparisons and kinetics, detailed overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage of the Tyr1605-Met(O)1606 peptide bond by ADAMTS13
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
specific cleavage of the long strings of ultra-large von Willebrand factor multimers. The specificity of ADAMTS13 for proteolysis of von Willebrand factor is facilitated by multiple cooperative contacts that bind ADAMTS13 to von Willebrand factor
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor to smaller less-active forms
-
-
?
VWF115 + H2O
?
-
a von Willebrand factor-derived peptide substrate, comprising amino acid residues 1554-1668 of von Willebrand factor
-
-
?
VWF115 + H2O
?
von Willebrand factor A2 domain fragment, residues 1554-1668
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
-
no activity with human fibrinogen, bovine serum albumin, and calf skin collagen
-
?
additional information
?
-
-
pro-von Willebrand factor is cleaved by pro-ADAMTS13 and by ADAMTS13
-
?
additional information
?
-
-
does not cleave GST-von Willebrand factor 64 which lacks 9 aa residues (E1660APDLVLQR1668)
-
-
?
additional information
?
-
-
PNGase-treated von Willebrand factor is more succeptible to proteolysis by ADAMTS13 and binds with increased affinity
-
-
?
additional information
?
-
-
ADAMTS13 binds to CD36, a transmembrane protein of endothelial cells and platelets, i.e. glycoprotein IV, not diminishing the proteolytic activity of ADAMTS13, but providing an anchor for ADAMTS13 on the surface of endothelial cells and platelets
-
-
?
additional information
?
-
-
ADAMTS13 contains eight thrombospondin type 1 repeats and binds to CD36, a transmembrane protein present on endothelial cells and platelets. CD36 also binds to thrombospondin-2 via three thrombospondin type 1 repeats in a manner competitive to ADAMTS13, overview
-
-
?
additional information
?
-
-
MDTCS domain modelling and substrate recognition mode analysis, overview
-
-
?
additional information
?
-
-
proteolysis can occur only once VWF has been unraveled from its globular conformation, either by high fluid shear stress in vivo or in the presence of denaturants in vitro, conditions that are able to promote the exposure of the VWF scissile bond
-
-
?
additional information
?
-
-
removal of newly released ultralarge-von Willebrand factor strings or bundles anchored on endothelial cells by ADAMTS13 occurs rapidly and efficiently in the presence and in the absence of fluid shear stress, suggesting that the cell-bound ultra large-von Willebrand factor polymers may be preferred substrates for ADAMTS13
-
-
?
additional information
?
-
thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays
-
-
?
additional information
?
-
-
thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays
-
-
?
additional information
?
-
-
ADAMTS 13 activity measurement using a collagen binding assay
-
-
?
additional information
?
-
-
binding specificities of wild-type ADAMTS13 and ADAMTS13-RYY to von Willebrand factor115, von Willebrand factor106, and full-length von Willebrand factor, overview
-
-
?
additional information
?
-
-
construction of substrate peptides VWF Asp1596-Ala1669, i.e. VWF74, VWF Asp1596-Ala1669 containing nitrotyrosine, i.e. VWF74-NT, or methionine sulfoxide, i.e. VWF74-MetSO, at position 1605 or 1606, respectively. VWF74 oxidized by peroxynitrite undergoes a severe impairment of its hydrolysis. Likewise, VWF74-MetSO is minimally hydrolyzed, whereas VWF74-NT is hydrolyzed only slightly more efficiently than VWF74, overview
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
-
molecular modeling of ADAMTS13 metalloprotease domain using its sequence homology to adamalysin II and the crystal structure
-
-
?
additional information
?
-
-
proteolysis can occur only once VWF has been unraveled from its globular conformation, either by high fluid shear stress in vivo or in the presence of denaturants in vitro, conditions that are able to promote the exposure of the VWF scissile bond. The ADAMTS13 C-terminal distal domains (TSP5-CUB) bind to a novel binding site in the C-terminal region of VWF, spanning residues 1874-2813 and including the VWF D4 domain, which, critically, is constitutively exposed on the surface of VWF in solution without flow. C-terminal VWF fragments, as well as an antibody specifically directed toward the VWF D4 domain, inhibit VWF proteolysis by ADAMTS13 under shear conditions
-
-
?
additional information
?
-
-
role for ADAMTS13 disintegrin-like domains in substrate recognition and proteolysis, homology modeling, overview. Residues Arg349, Leu350, and Val352 are predicted to form a cluster on the surface of the ADAMTS13 disintegrin-like domain immediately adjacent to the active-site cleft
-
-
?
additional information
?
-
-
the positively charged Arg349 on ADAMTS13 appears to directly interact with the negatively charged Asp1614 on the von Willebrand factor-A2 domain. This seemingly weak interaction between the disintegrin and VWF-A2 appears to be essential for efficient catalysis of von Willebrand factor under static/denaturing conditions. Molecular modeling of the involvement of the disintegrin domain of ADAMTS13 in von Willebrand factor processing, overview
-
-
?
additional information
?
-
plasmin cleaves and ultimately inactivates the enzyme
-
-
?
additional information
?
-
-
plasmin cleaves and ultimately inactivates the enzyme
-
-
?
additional information
?
-
-
the enzyme cleaves a susceptible tyrosine-methionine bond located between amino acids 9 and 10 in a synthetic 77 amino acid substrate. Amino acid 3 is a glutamic acid residue to which the fluorescent 2-(N-methylamino)benzoyl group is covalently bonded. Amino acid 13 is a glycine residue to which the quenching agent 2,4 dinitrophenol is attached. Upon cleavage of the tyrosine-methionine bond, the quenching effect of the 2,4 dinitrophenol is reduced, and excitation of-(N-methylamino)benzoyl results in fluorescent emission measured at 440 nm
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
important role for ADAMTS13 in preventing excessive spontaneous Weibel-Palade body secretion, and in the regulation of leukocyte adhesion and extravasation during inflammation
-
-
?
additional information
?
-
-
assay on the fluorogenic substrate FRETS-vWF73
-
-
?
additional information
?
-
-
no activity in von Willebrand factor-deficient or ADAMTS13-deficient mice with the recombinant substrate of human origin. Differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
additional information
?
-
-
differences in susceptibility to cleavage of recombinant von Willebrand factor by different species need to be considered when interpreting the physiology of human recombinant von Willebrand factor from results of tests in animal models
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
von Willebrand factor + H2O
2 peptides
-
rapid physiological process that occurs on endothelial surfaces, reduced activity results in thrombotic thrombocytopenic pupura
-
?
von Willebrand factor + H2O
2 peptides of 140 kD and 65 kD
-
cleavage of peptide bond Tyr842-Met843
-
?
von Willebrand factor + H2O
2 peptides of 176 kD and 140 kD
-
rapid physiological process that occurs on endothelial surfaces, activity is reduced by 87-100% in patients with thrombotic thrombocytopenic pupura
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
von Willebrand factor 115 + H2O
10000 Da fragment of von Willebrand factor 115 + 7000 Da fragment of von Willebrand factor 115
-
von Willebrand factor is cleaved at the Tyr1605-Met1606 bond in the von Willebrand factor A2 domain
-
-
?
proteins + H2O
peptides
enzyme is involved in thrombotic thrombocytopenic purpura
-
?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
-
cleavage of the peptide bond Tyr842-Met843 within the A2 domain, enzyme deficiency causes lethal thrombotic thrombocytopenic purpura
-
?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
-
either congenital or acquired defects of the enzyme lead to thrombotic thromcytopenic purpura, cleavage of the peptide bond bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
-
?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
-
large multimeric substrate, cleavage of the peptide bond Tyr842-Met843 within the A2 domain
-
?
von Willebrand factor + H2O
2 peptides of 140 kDa and 176 kDa
-
protein from plasma of patients suffering type I von Willebrand disease is more susceptible to proteolysis by the enzyme due to amino acid polymorphism heterozygous at position Tyr/Cys1584, phenotypic parameters, cleavage of the peptide bond Tyr842-Met843 within the A2 domain
-
?
von Willebrand factor + H2O
?
-
-
669524, 678918, 678964, 679396, 680535, 680695, 681661, 681662, 681663, 682523, 682525, 682898, 682901, 682939, 710827, 711086, 711559, 711564, 711565, 711569, 711571, 711572, 711575, 711809, 712568, 713079, 713189, 713533, 713534, 713536, 719881, 720367, 720833, 753897, 754157, 754522, 755583
-
-
?
von Willebrand factor + H2O
?
-
cleavage of peptide bond Tyr842-Met843, large hemostatically active multimers are cleaved to smaller less active forms, increased proteolytic degradation in patients suffering from von Willebrand disease typ 2A
-
?
von Willebrand factor + H2O
?
cleavage of peptide bond Tyr842-Met843, rapid degradation of multimers to smaller fragments, decreased activity results in bone marrow transplant-associated thrombotic microangiopathy and thrombotic thrombocytopenic pupura
-
?
von Willebrand factor + H2O
?
-
decrease of the multimeric pattern of enzyme and decreased activity results in bone marrow transplant-associated thrombotid microangiopathy
-
?
von Willebrand factor + H2O
?
-
enzyme deficiency causes lethal thrombotic thrombocytopenic purpura, cleavage of peptide bond Tyr1605-Met1606 resulting in limited platelet accumulation in microvascular thrombi (Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275)
-
?
von Willebrand factor + H2O
?
-
the cleavage site is exposed to the enzyme by conformational changes due to shear stress in the plasma, decrease of the multimeric pattern of enzyme and decreased activity results in bone marrow transplant-associated thrombotic microangiopathy, cleavage of peptide bond Tyr842-Met843, large hemostatically active multimers are cleaved to smaller less active forms, increased proteolytic degradation in patients suffering von Willebrand disease typ 2A
-
?
von Willebrand factor + H2O
?
-
cleavage of Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
-
-
?
von Willebrand factor + H2O
?
-
ADAMTS13 cleaves at the peptide bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
-
-
?
von Willebrand factor + H2O
?
-
ADAMTS13 cleaves the bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275
-
-
?
von Willebrand factor + H2O
?
-
amino acid position C1584 is necessary for enhanced von Willebrand factor proteolysis by ADAMTS13
-
-
?
von Willebrand factor + H2O
?
ADAMTS13 efficiently cleaves only the Tyr842-Met843 bond within the central A2 domain of multimeric von Willebrand factor (i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275)
-
-
?
von Willebrand factor + H2O
?
-
a catalysis-deficient ADAMTS13 P475S mutant does not show VWF-induced changes in conformation
-
-
?
von Willebrand factor + H2O
?
-
ADAMTS13 cleaves ultra-large von Willebrand factor multimers
-
-
?
von Willebrand factor + H2O
?
-
force-induced von Willebrand factor A2 domain unfolding of the substrate facilitates cleavage, using single VWF A1A2A3 tridomain polypeptides, structural destabilization of A1A2A3 was induced by 5- to 80-pN forces
-
-
?
von Willebrand factor + H2O
?
-
persistently elevated levels of von Willebrand factor in plasma during and after liver transplantation, while plasma levels of ADAMTS13 dropp during transplantation
-
-
?
von Willebrand factor + H2O
?
-
specific cleavage of ultra-large von Willebrand factor multimers
-
-
?
von Willebrand factor + H2O
?
-
ADAMTS-13 has thiol reductase activity limited towards von Willebrand factor
-
-
?
von Willebrand factor + H2O
?
-
ADAMTS13 specifically cleaves von Willbrand factor A2 domain between Tyr1605 and Met1606
-
-
?
von Willebrand factor + H2O
?
-
cleavage occurs at strand beta4 (Tyr1605-Met1606) in the structural core of the A2 domain. Ca2+ binding stabilizes the A2 domain and impedes its unfolding, and consequently protects it from cleavage by ADAMTS13
-
-
?
von Willebrand factor + H2O
?
-
the disulfide-bond-reducing activity of ADAMTS-13 prevents covalent lateral association and increased platelet adherence of plasma-type von Willebrand factor multimers induced by high fluid shear stress
-
-
?
von Willebrand factor + H2O
?
-
von Willebrand factor A2 domain unfolding is required for proteolysis by ADAMTS13, the ADAMTS13 cleavage site is at Tyr1605-Met1606
-
-
?
von Willebrand factor + H2O
?
-
von Willebrand factor is also susceptible to cleavage by ADAMTS13 when incorporated in a thrombus
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
-
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleavage of von Willebrand factor strings secreted from stimulated and unstimulated HUVECs occurs at the position 1605-6 of the von Willebrand factor A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleaves the Tyr1605-Met1606 bond in the VWF A2 domain, mechanisms of VWF recognition, cleavage analysis and kinetics under static and flow conditions, overview
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS-13 cleaves von Willebrand factor (VWF) exclusively at the Tyr1605-Met1606 peptide bond in the A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor 140-kD fragment + von Willebrand factor 176-kD fragment
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor to smaller less-active forms
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 specifically cleaves von Willebrand factor multimers at the site of the Tyr1605-Met1606 bond of the VWF-A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage at the Tyr1605-Met1606 bond within the van Willebrand factor A2 domain
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage can also occur at the surface of endothelial cells. ADAMTS13 that is prebound to endothelial cells exhibits increased proteolysis of VWF as compared with ADAMTS13 present only in solution. Thus, cleavage of VWF occurs mainly at the endothelial cell surface
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
cleavage of ultra large von Willebrand multimers into smaller fragments
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
specific cleavage of the long strings of ultra-large von Willebrand factor multimers
-
-
?
von Willebrand factor + H2O
von Willebrand factor fragments
-
ADAMTS13 cleaves von Willebrand factor to smaller less-active forms
-
-
?
additional information
?
-
-
ADAMTS13 binds to CD36, a transmembrane protein of endothelial cells and platelets, i.e. glycoprotein IV, not diminishing the proteolytic activity of ADAMTS13, but providing an anchor for ADAMTS13 on the surface of endothelial cells and platelets
-
-
?
additional information
?
-
-
ADAMTS13 contains eight thrombospondin type 1 repeats and binds to CD36, a transmembrane protein present on endothelial cells and platelets. CD36 also binds to thrombospondin-2 via three thrombospondin type 1 repeats in a manner competitive to ADAMTS13, overview
-
-
?
additional information
?
-
-
MDTCS domain modelling and substrate recognition mode analysis, overview
-
-
?
additional information
?
-
-
proteolysis can occur only once VWF has been unraveled from its globular conformation, either by high fluid shear stress in vivo or in the presence of denaturants in vitro, conditions that are able to promote the exposure of the VWF scissile bond
-
-
?
additional information
?
-
-
removal of newly released ultralarge-von Willebrand factor strings or bundles anchored on endothelial cells by ADAMTS13 occurs rapidly and efficiently in the presence and in the absence of fluid shear stress, suggesting that the cell-bound ultra large-von Willebrand factor polymers may be preferred substrates for ADAMTS13
-
-
?
additional information
?
-
thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays
-
-
?
additional information
?
-
-
thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays
-
-
?
additional information
?
-
plasmin cleaves and ultimately inactivates the enzyme
-
-
?
additional information
?
-
-
plasmin cleaves and ultimately inactivates the enzyme
-
-
?
additional information
?
-
important role for ADAMTS13 in preventing excessive spontaneous Weibel-Palade body secretion, and in the regulation of leukocyte adhesion and extravasation during inflammation
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ba2+
Ca2+
Mg2+
Zn2+
additional information
Ba2+
-
complete proteolysis is observed at 37°C in the presence of BaCl2 while about 25% von Willebrand factor still binds to collagen when BaCl2 supplementation is omitted
Ba2+
-
barium ions stimulate ADAMTS13 activity in citrated plasma but not in citrate-free plasma, cleavage of von Willebrand factor by recombinant ADAMTS13 is activated up to 200fold by barium ions
Ca2+
-
Ca2+ binding site with coordinates Asp173, Cys281, Asp284, and Met249, activating
Ca2+
metalloprotease, conserved binding site using Glu83, ASp173, Cys281, Asp284
Ca2+
-
in citrate-anticoagulated plasma activity is enhanced about 3fold by calcium ions (up to 5 mM), cleavage of von Willebrand factor by recombinant ADAMTS13 is activated up to 200fold by calcium ions
Ca2+
-
highly dependent on, Ca2+ induces a conformational change in ADAMTS13, but only under low-ionic-strength conditions, which is abolished in mutants E83A and D173A. The Ca2+-binding site in proximity to the ADAMTS13 active site comprises Glu184, Asp187, and Glu212, identified by homology modelling. Mutagenesis of these residues within this site to alanine dramatically attenuates the KD(app) for Ca2+ of ADAMTS13, and for D187A and E212A also reduces the Vmax to approximately 25% of wild-type. The major influence of Ca2+ on ADAMTS13 function is mediated through binding to a high affinity site adjacent to its active site cleft. The short sequence spanning residues 162 to 168 of the metalloprotease domain is not a Ca2+ binding site
Ca2+
-
ADAMTS13 activity in the reaction buffer containing 0.9 mM Ca2+ without incubation is enhanced 2.7times compared to the value determined in the absence of Ca2+. The activity of ADAMTS13 in the presence of 10 mM Ca2+ is enhanced 3-5fold
Ca2+
-
the catalytic domain of the enzyme possesses up to three putative Ca2+ binding sites
Zn2+
-
in citrate-anticoagulated plasma activity is enhanced about 2fold by zinc ions (1 mM), cleavage of von Willebrand factor by recombinant ADAMTS13 is activated up to 200fold by zinc ions
Zn2+
-
required, three active sites His and catalytic residues Glu coordinate a catalytic Zn2+ ion
Zn2+
-
the catalytic domain of the enzyme possesses one Zn2+ binding site. Zn2+ is required to stabilize enzyme structure at physiologic temperature
additional information
-
enzyme is a member of the ADAMTS metalloprotease family, disintegrin and metalloproteinase with thrombospondin type I motif
additional information
-
metalloprotease, contains an essential Zn2+ binding site, no activtion by Zn2+ and Mn2+
additional information
-
Ca2+ is the most potent activating divalent cation out of Ca2+, Ba2+, Mg2+, Mn2+, Ni2+, and Cu2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ca2+
enzyme catalytic activity in blood plasma is tuned by varying buffer calcium, with lower divalent ion concentrations enhancing cleavage
Cl-
-
Chloride ions inhibit von Willebrand factor hydrolysis by ADAMTS-13 of the A1-A2-A3 and A1-A2 domains in the presence of either urea or high shear stress, whereas this effect is either absent or negligible when using A2 and A2-A3 domains
H2O2
treatment with 25 nM myeloperoxidase plus 50 microM H2O2 reduces ADAMTS13 activity by >85%. Residues Met249, Met331, and Met496 in important functional domains of ADAMTS13 are oxidized to methionine sulfoxide in an HOCl concentration-dependent manner
heparin
-
inhibits ADAMTS13 activity through inhibition of enzyme binding to endothelial cell surfaces, overview
HOCl
-
HOCl can oxidize methionine to methionine sulfoxide and tyrosine to chlorotyrosine, oxidation of VWF A2 peptide, at Met1606 and Tyr1605, markedly impairs ADAMTS13 cleavage. Oxidative modification by myeloperoxidase/H2O2 is similar to that produced by HOCl
peroxynitrite
-
formation of methionine sulfoxide by peroxynitrite at position 1606 of von Willebrand factor inhibits its cleavage by ADAMTS-13 a prothrombotic mechanism in diseases associated with oxidative stress, overview. Oxidation by peroxynitrite of purified VWF multimers inhibits ADAMTS-13 hydrolysis, but does not alter their electrophoretic pattern nor their ability to induce platelet agglutination by ristocetin. In vitro treatment of ADAMTS-13 with peroxynitrite over a concentration ranging from 0.050 to 0.250 mM causes a complete inhibition of the protease activity of the enzyme
Trypsin
-
inhibits ADAMTS13 activity through inhibition of enzyme binding to endothelial cell surfaces, overview
-
VWFA2 domain
-
a C-terminal 32 kDa fragment of VWF, soluble VWFA2 domain effectively inhibits the binding of ADAMTS13 to immobilized VWFA2, and completely inhibits the interaction between ADAMTS13 and immobilized 64 kDa VWFA1A2A3 fragment
-
W688X6-1
-
the monoclonal antibody W688X6-1 shows dose-dependent inhibitory activity toward ADAMTS13-mediated hydrolysis
-
WH2-22-1A
-
the monoclonal antibody WH2-22-1A shows dose-dependent inhibitory activity toward ADAMTS13-mediated hydrolysis
-
Zn2+
-
ADAMTS13 activity is undetectable at concentrations of zinc ions above 3 mM Zn2+
additional information
-
no inhibition by iodoacetamide, leupeptin, and serine protease inhibitors DFP, PMSF, aprotinin
-
additional information
enzyme is inhibited by plasma from an individuum with acquired thrombotic thrombocytopenic pupura
-
additional information
-
enzyme is inhibited by plasma from an individuum with acquired thrombotic thrombocytopenic pupura
-
additional information
-
inhibitory autoantibodies from plasma of 3 patients with acquired thrombotic thrombocytopenic purpura, epitope mapping
-
additional information
-
inhibition by autoantibodies from patients with acquired thrombotic thrombocytopenic purpura
-
additional information
-
no inhibition by iodoacetamide, leupeptin, and serine protease inhibitorsDFP, PMSF, aprotinin
-
additional information
-
inhibition of the enzyme by IgG from a patient with idiopathic thrombotic thrombocytopenic pupura
-
additional information
-
increasing concentrations of BaCl2 (up to 5 mM) have little effect on the activity of ADAMTS13 at pH 7.4, Mg(SO4) and Cu(SO4) have little effect on the activity of ADAMTS13 at pH 7.4
-
additional information
-
proteolysis of ADAMTS-13 by thrombin leads to a 8fold reduction in affinity for von Willebrand factor
-
additional information
-
malaria patients possess high ADAMTS13 autoantibodies levels as well as endogenous ADAMTS13 inhibitors compared to healthy controls
-
additional information
-
construction and screening of an epitope peptide library, e.g. of epitope-A, i.e. a C-terminus of spacer domain from Arg670 to Gln684, and epitope-B, i.e. Pro618 to Glu641 in the middle of spacer domain. Synthetic epitope-B peptide inhibits the cleavage of VWF by ADAMTS13, while the synthetic epitope-A peptide does inhibit not as efficiently as epitope-B. Elimination of four amino acids from either sides of epitope-B terminus markedly reduces the inhibitory effect
-
additional information
-
inhibitory anti-ADAMTS 13 antibodies, measurement and clinical application, overview
-
additional information
-
C-terminal VWF fragments, as well as an antibody specifically directed toward the VWF D4 domain, inhibit VWF proteolysis by ADAMTS13 under shear conditions
-
additional information
-
specific blockade of von Willebrand factor string cleavage by antibody to ADAMTS-13, overview
-
additional information
-
substrate modified by treatment with PNGase F to remove complex N-linked glycan structures results in increased ADAMTS13 activity
-
additional information
-
auto-antibodies against ADAMTS13 lead to ADAMTS13 deficiency, which causes e.g. thrombotic thrombocytopenic purpurea, overview
-
additional information
-
influenza A infection is sufficient to trigger thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor, overview
-
additional information
-
an endogenous ADAMTS13 inhibitor can cause enzyme deficiency
-
additional information
-
infection with Plasmodium falciparum inhibits ADAMTS13. ADAMTS13 activity in normal plasma is reduced by approximately 60% after pooled normal plasma is incubated in a 3:1 mix with malarial plasma for 30 min
-
additional information
-
protease activity of ADAMTS13 is controlled not by natural inhibitors but by conformational changes in its substrate, which are induced when von Willebrand factor is subject to elevated rheologic shear forces
-
additional information
-
monoclonal antibody SZ34 inhibits proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions (IC50 0.05 mg/ml). Thrombospondin-1 decreases the rate of von Willebrand factor proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of von Willebrand factor
-
additional information
exposure of ADAMTS13 to activated human neutrophils results in oxidation of residues Met249, Met331, and Met496 in important functional domains of ADAMTS13. ADAMTS13 treated with either neutrophil elastase or plasmin is inhibited to a lesser extent, especially in the presence of plasma.
-
additional information
-
exposure of ADAMTS13 to activated human neutrophils results in oxidation of residues Met249, Met331, and Met496 in important functional domains of ADAMTS13. ADAMTS13 treated with either neutrophil elastase or plasmin is inhibited to a lesser extent, especially in the presence of plasma.
-
additional information
-
ADAMTS-13 activity is evaluated in a model of sepsis induced by cecum ligature and puncture in wild-type and Vwf-/- mice. In wild-type mice, cecum ligature and puncture-induced sepsis elicits a significant ADAMTS-13 decrease, and a strong negative correlation exists between von Willebrand factor, VWF, and ADAMTS-13. In Vwf-/- mice, cecum ligature and puncture also induces severe sepsis, but ADAMTS-13 is not significantly diminished
-
additional information
-
CCl4 at concentration of 6.5 mM does not directly inhibit the activity of ADAMTS-13
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
plasmin
truncation of the enzyme by plasmin enhances its activity in blood plasma
-
Rituximab
-
a monoclonal anti-CD 20 antibody, Rituximab leads to a prompt reduction in IgG antibody levels, followed by an increase in ADAMTS 13 activity increases. However, in patients receiving Rituximab electively, normalisation of ADAMTS 13 enzyme activity may be delayed for up to 3 months
-
von Willebrand factor
binding to substrate von Willebrand factor D4 allosterically activates ADAMTS13, increasing its catalytic activity. Binding also positions ADAMTS13 on the substrate where it can act rapidly when shear stress exposes the scissile bond in the adjacent A2 domain
-
von Willebrand factor
-
the enzyme is conformationally activated by von Willebrand factor which engages the TSP8-CUB2 domains, inducing the conformational change that disrupts the CUB1-spacer domain interaction and thereby activates the enzyme
-
additional information
-
low salt concentrations activate the proteolytic activity
-
additional information
-
cleavage of von Willebrand factor A2 requires the force-induced A2 unfolding
-
additional information
-
inhibition of ADAMTS13 by auto-antibodies is reversed by rituximab, overview
-
additional information
-
mild denaturation of fluid shear stress increase the hydrolysis of von Willebrand factor
-
additional information
-
substrate modified by alpha2-3,6,8,9-neuraminidase from Arthrobacter ureafaciens removing alpha2-3- and alpha2-6-linked sialic acid results in reduced ADAMTS13 activity
-
additional information
-
coagulation factor VIII, platelet glycoprotein 1balpha, and heparin sulfate accelerate the cleavage of von Willebrand factor
-
additional information
-
in the absence of factor VIII, lyophilized platelets increase the formation of cleavage product by 2-3fold under fluid shear stresses. However, in the presence of physiological concentration of factor VIII (1 nM), the formation of von Willebrand factor cleavage product increases dramatically as a function of increasing platelets (150000 per microliter) with the maximal rate enhancement of about 8fold
-
additional information
antibodies that recognize domains T67, T8, and CUB domains have additive effects. Binding activates ADAMTS13 up to 4.2fold at pH 7.4, but antibodies have markedly decreased effects on ADAMTS13 activity at pH 6
-
additional information
removal of the C-terminal domain of the enzyme by activated coagulation factor XI or alpha-thrombin causes an increase in enzyme activity
-
additional information
-
CCl4 at concentration of 6.5 mM does not directly enhance the activity of ADAMTS-13
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00662
DREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRA
-
pH 7.5, 25°C, recombinant enzyme
0.00065
von Willebrand factor 115
-
wild type enzyme, in 20 mM Tris-HCl (pH 7.8), 150 mM NaCl, 5 mM CaCl2, at 37°C
-
0.00086
VWF115
mutant R568K/F592Y/R660K/Y661F/Y665F, pH not specified in the publication, temperature not specified in the publication
-
0.00154
VWF115
wild-type, pH not specified in the publication, temperature not specified in the publication
-
0.022
VWF73 peptide
-
pH 6.0, 37°C, recombinant ADAMTS13 6-amino-acid-deletion mutant
-
additional information
additional information
-
Km: 0.0032 mM for FRETS-VWF73, a fluorescent synthetic peptide, corresponding to residues Asp1596-Arg1668 of von Willebrand factor domain A2 and containing the Tyr1605-Met1606 bond cleaved by ADAMTS13
-
additional information
additional information
-
Ca2+ binding kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
-
kinetic analysis of ADAMTS13 disintegrin-like domain mutants
-
additional information
additional information
-
kinetics of ADAMTS13 disintegrin domain mutants with substrate VWF115, overview
-
additional information
additional information
-
Michaelis-Menten ADAMTS-13/A1A2A3 binding kinetics, overview
-
additional information
additional information
-
Michaelis-Menten steady-state kinetics, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.72
DREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRA
-
pH 7.5, 25°C, recombinant enzyme
additional information
additional information
-
kcat: 0.83 per min for FRETS-VWF73, a fluorescent synthetic peptide, corresponding to residues Asp1596-Arg1668 of von Willebrand factor domain A2 and containing the Tyr1605-Met1606 bond cleaved by ADAMTS13
-
0.52
von Willebrand factor 115
-
wild type enzyme, in 20 mM Tris-HCl (pH 7.8), 150 mM NaCl, 5 mM CaCl2, at 37°C
-
0.62
VWF115
mutant R568K/F592Y/R660K/Y661F/Y665F, pH not specified in the publication, temperature not specified in the publication
-
0.71
VWF115
wild-type, pH not specified in the publication, temperature not specified in the publication
-
1.56
VWF73 peptide
-
pH 6.0, 37°C, recombinant ADAMTS13 6-amino-acid-deletion mutant
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
821
von Willebrand factor 115
-
wild type enzyme, in 20 mM Tris-HCl (pH 7.8), 150 mM NaCl, 5 mM CaCl2, at 37°C
-
410
VWF115
wild-type, pH not specified in the publication, temperature not specified in the publication
-
830
VWF115
mutant R568K/F592Y/R660K/Y661F/Y665F, pH not specified in the publication, temperature not specified in the publication
-
74
VWF73 peptide
-
pH 6.0, 37°C, recombinant ADAMTS13 6-amino-acid-deletion mutant
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
C-terminal fragments competitive inhibition binding, kinetics, overview
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
intracellular and secreted forms of ADAMTS13 show comparable proteolytic activity
additional information
-
more ADAMTS-13-mediated cleavage of the relatively few von Willebrand factor strings secreted at a slow rate from unstimulated HUVECs, and less ADAMTS-13 cleavage of the many von Willebrand factor strings secreted rapidly in response to cell stimulation
additional information
-
unpurified blood plasma ADAMTS13 has a specific activity of 0.01 units/mg, purified blood plasma ADAMTS13 has a specific activity of 300 units/mg (25057fold purification)
additional information
-
determination of ADAMTS13 antigen and proteolytic activity in murine plasma, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5 - 8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
-
assay at
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
652431, 652481, 653678, 667102, 667122, 668071, 668076, 668352, 669457, 669524, 670053, 670893, 670933, 670936, 670946, 670948, 677437, 678918, 678919, 678964, 678966, 679396, 680056, 680535, 680695, 680929, 681661, 681662, 681663, 682523, 682525, 682898, 682901, 682939
-
-
brenda
-
710826, 710827, 711086, 711559, 711560, 711563, 711564, 711565, 711566, 711567, 711569, 711570, 711571, 711572, 711574, 711575, 711576, 711809, 712070, 712099, 712115, 712127, 712195, 712203, 712393, 712568, 712569, 712570, 712899, 712900, 713079
-
-
brenda
-
713189, 713347, 713381, 713400, 713531, 713533, 713534, 713535, 713560, 713561, 713562, 719160, 719162, 719163, 719761, 719881, 720345, 720346, 720367, 720833
-
-
brenda
-
SwissProt
brenda
enzyme is a member of the ADAMTS metalloprotease family, disintegrin and metalloproteinase with thrombospondin type I motif
-
-
brenda
genetic analysis of a woman with a family history of chronic recurrent thrombotic thrombocytopenic purpurea and undetectable plasma levels of ADAMTS13 reveals two missense mutations in the heterozygous state: Val88Met substitution in the metalloprotease domain and Gly1239Val substitution in the first CUB domain of ADAMTS13
-
-
brenda
paroxysmal and chronic atrial fibrillation patients and healthy controls
-
-
brenda
wild-type strain C57BL/6J mice, the isogenic von Willebrand factor-deficient strain 129x1/SvJ, and the ADAMTS13-deficient gene knock-out strain CAST/EiJ
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
in cerebral corpora amylacea, that occur in aging brains and in patients with neurodegenerative conditions
brenda
in astrocytes of aging brains and patients with neurodegenerative conditions. Corporae amylaceae include glycosylated material, ubiquitin, and an assortment of proteins derived from neuronal cytoplasm. Many of these proteins are not specifically localized to neurons or astrocytes, some components of corpora amylacea, such as complement proteins, are most abundantly expressed outside the central nervous system. Corporae amylaceae can result from a conglomeration of interacting proteins from degenerating neurons and from extravasated blood elements released after transient breakdown of the blood-brain barrier
brenda
-
primary renal cortical cell cultures, real-time PCR and immunohistochemic analysis, overview
brenda
thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays
brenda
-
in both proximal and distal in healthy persons and in patients with renal disorders, e.g. tubulopathy
brenda
additional information
-
cord blood. Neonates and children have a percentage ADANTS-13 activity similar to adults. 28/38 newborns have percentage activity within the normal range of healthy adults, 10 have significantly lower percentage activity that normalizes by day 2-3
brenda
-
-
650714, 669524, 670946, 677437, 678918, 678919, 678964, 678966, 679396, 680535, 680695, 680929, 681662, 681663, 682523, 682901, 682939, 719761, 719881, 720345, 720367, 754522, 755614
brenda
-
ADAMTS-13 activity in type 1, 2A, and 2B von Willebrand disease is higher than in healthy controls, but lower than in type 3 von Willebrand disease
brenda
-
ADAMTS13 activity decreases in a time-dependent manner during systemic inflammation
brenda
-
no severe ADAMTS13 deficiency is detected in patients with sickle cell disease
brenda
-
of normal non-pregnant woman, pregnant and post-delivery women. Between the non-pregant state and the 6-11 week period of pregnancy, there is no statistical difference in the levels of ADAMTS13 activity. Starting from the 12-16 week, group differences become significant. the late postpartum shows the highest level of protease activity, including in the non-pregant state. In non-pregnant women, protease activity is significantly lower in nulliparous compared to parous women. In pregant and psot-delivery women, mean ADAMTS13 actrivity is slightly lower in primigravidae than in multigravidae
brenda
-
von Willebrand factor-cleaving protease activity remains at the intermediate level in thrombotic thrombocytopenic purpura
brenda
levels of ADAMTS13 are lower and levels of von Willebrand Factor are higher in young patients with cardiovascular disease compared to healthy individuals
brenda
-
ADAMTS13 associates to the platelet surface via binding of membrane-integrated CD36
brenda
-
ADAMTS13 associates to the cell surface via binding of membrane-integrated CD36
brenda
-
obtained from collagenase-digested human umbilical veins, ADAMTS-13 is released directly from the Golgi to the cell exterior without an organelle storage site, e.g. a cytoplasmic granule
brenda
-
ADAMTS13 is secreted by almost all tissues but primarily by hepatic stellate cells
brenda
-
retinoid enriched, i.e. lipocyte, secretes the enzyme
brenda
-
the dramatically increased ADAMTS-13 protein and proteolytic activity in the activated hepatic stellate cells in vitro and in vivo may be important part of functions of activated hepatic stellate cells, perhaps by modulating the processes of liver regeneration or formation of liver fibrosis after various insults
brenda
-
secretes the enzyme, ADAMTS13 activity in hepatic carcinoma, liver cirrhosis due to viral infection, primary biliary cirrhosis, cholestasis, and biliary atresia, overview
brenda
-
-
650102, 650710, 650712, 650717, 650725, 651439, 652431, 652481, 653678, 710827, 711560, 711563, 711564, 711565, 711567, 711569, 711570, 711571, 711574, 711575, 711576, 711579, 711809, 712070, 712099, 712115, 712127, 712195, 712203, 712393, 712568, 712569, 712899, 712900, 713079, 713347, 713381, 713400, 713531, 713533, 713534, 713536, 713560, 713561
brenda
-
from paroxysmal and chronic atrial fibrillation patients and healthy controls, ADAMTS13 contents and activities, overview
brenda
-
persistently elevated levels of von Willebrand factor in plasma during and after liver transplantation, while plasma levels of ADAMTS13 dropp during transplantation
brenda
additional information
-
ADAMTS-13 levels in healthy controls and patients with disseminated intravascular coagulation
brenda
additional information
-
activity is undetectable in heart, brain, kidney and testis
brenda
additional information
-
activity is undetectable in heart, brain, kidney and testis
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
homogeneous distribution of wild-type ADAMTS13 in cis-Golgi and endoplasmic reticulum compartments. Reduction of ADAMTS13(Val88Met) in both compartments. ADAMTS13(Gly1239Val) fails to reach the cis-Golgi compartment and remains in the endoplasmic reticulum
brenda
-
homogeneous distribution of wild-type ADAMTS13 in cis-Golgi and endoplasmic reticulum compartments. Reduction of ADAMTS13(Val88Met) in both compartments. ADAMTS13(Gly1239Val) fails to reach the cis-Golgi compartment and remains in the endoplasmic reticulum
brenda
-
ADAMTS13 binds to endothelial cells in a specific, reversible, and time-dependent manner with a Kd of 58 nM. Binding requires the COOH-terminal thrombospondin type 1 repeats of the protease. Binding is inhibited in the presence of heparin and by trypsin treatment of the cells
brenda
-
-
-
710826, 710827, 711560, 711563, 711564, 711565, 711567, 711569, 711571, 711574, 711575, 711576, 711579, 711809, 712070, 712115, 712127, 712195, 712203, 712393, 712568, 712569, 712899, 712900, 713079, 713347, 713381, 713400, 713531, 713532, 713534, 713536, 713560, 713561
brenda
-
plasma
-
brenda
-
ADAMTS-13 is released directly from the Golgi to the cell exterior without an organelle storage site, e.g. a cytoplasmic granule
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
malfunction
-
a severe functional deficiency of ADAMTS13 (activity lower than 10%) is associated with thrombotic thrombocytopenic purpura
malfunction
-
ADAMTS13 deficiency is associated with thrombotic thrombocytopenia purpura with microangiopathic hemolytic anemia and thrombocytopenia
malfunction
-
lack of blood plasma ADAMTS13 activity results in thrombotic thrombocytopenic purpura
malfunction
functional deficiency of the enzyme causally assists in the pathology of thrombotic thrombocytopenic purpura
malfunction
reduced enzyme activity is associated with arterial thrombosis
physiological function
-
ADAMTS 13 is required for the cleavage of ultra large von Willebrand multimers into smaller fragments, as they are released from endothelial cells. A deficiency of ADAMTS 13 or inhibition of its action by antibodies, identified in many cases of acquired thrombotic thrombocytopenic purpura, TTP, results in adhesion and aggregation of platelets to ultra large von Willebrand multimers, small vessel thrombosis, primarily capillaries and arterioles and associated microvascular symptoms. Relationship of ADAMTS 13 activity and IgG antibody to ADAMTS 13 and cardiac presentation, phenotypes, overview. The higher troponin T levels in patients with elevated IgG antibody levels to ADAMTS 13, is associated with an increased acute mortality and morbidity
physiological function
-
ADAMTS-13 deficiency is the cause for thrombotic thrombocytopenic purpura is an acute life threatening disorder, characterised by thrombocytopenia, microangiopathic haemolytic anaemia and multi organ microvascular thrombi that results in variable clinical symptoms
physiological function
-
ADAMTS-13 deficiency is the cause for thrombotic thrombocytopenic purpura, CD36 is involved, phenotype and clinical treatmemnts, detailed overview
physiological function
-
ADAMTS-13 regulates hemostasis by cleaving the folded A2 domain of von Willebrand factor. The cleavage is regulated by forces as it occurs in flowing blood. Mechanical regulation of VWF cleavage by ADAMTS-13 at the level of single A1A2A3 tridomain, overview
physiological function
-
ADAMTS13 activity inhibition causes thrombotic thrombocytopenic purpura, TTP. Microthrombi are prominent in the heart, kidneys, pancreas, and adrenal glands
physiological function
-
ADAMTS13 deficiency is responsible for idiopathic, i.e. primary or sporadic, thrombotic thrombocytopenia purpura, TTP, characterized by thrombocytopenia, a microangiopathic hemolytic anemia, but not for thrombotic thrombocytopenia purpura/hemolytic uremic syndrome, TTP/HUS, or disseminated intravascular coagulation, depending on the degree of the coagulopathy, caused by quinine, overview
physiological function
-
ADAMTS13 deficiency plays a central role in the pathogenesis of hereditary or acquired idiopathic thrombotic thrombocytopenic purpura
physiological function
-
ADAMTS13 deficiency, along with an inhibitory antibody found in most patients, is involved in thrombotic thrombocytopenic purpura. Patients with human immunodeficiency virus infection can have a thrombotic thrombocytopenic purpura-like illness, phenotypes, detailed overview
physiological function
-
ADAMTS13 deficiency, due to different reasons, causes thrombotic thrombocytopenic purpurea, which contributes to the prothrombotic coagulation abnormalities preceding organ dysfunction systemic inflammatory response syndrome, overview
physiological function
-
ADAMTS13 is a metalloprotease that limits admission and persistence of unusually large VWF multimers in the circulation, where they form abnormally large thrombi in the microvasculature. Thrombotic thrombocytopenic purpura is caused by congenital ADAMTS13 deficiency, and ADAMTS13 deficiency is an important cause of thrombocytopenia during pregnancy. Thrombotic thrombocytopenic purpura is a rare but life-threatening disease characterized by microangiopathic hemolytic anemia and consumptive thrombocytopenia leading to disseminated microvascular thrombosis
physiological function
-
ADAMTS13 is a multidomain protease that limits platelet thrombogenesis through the cleavage of von Willebrand factor and contributes to inhibition of platelet aggregation. Accelerated thrombus growth occurs in truncated mutant Adamts13S/S mice compared with wild-type full-length Adamts13L/L mice, indicating that the distal C-terminally truncated form of mouse ADAMTS13 has significantly reduced activity in vivo
physiological function
-
ADAMTS13 is a plasma metalloprotease that cleaves ultra-large von Willebrand factor multimers to generate less thrombogenic fragments
physiological function
-
ADAMTS13 is a plasma metalloprotease that regulates the size of the von Willebrand factor multimers. Genetic or acquired deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura, TTP
physiological function
-
ADAMTS13 is a protease that cleaves the von Willebrand factor, VWF, within intact blood vessels under shear stress. ADAMTS13 is implicated in thrombotic thrombocytopenic purpura pathogenesis, overview
physiological function
-
ADAMTS13 is involved in thrombotic thrombocytopenic purpura
physiological function
-
ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion, limiting platelet-dependent thrombus growth. ADAMTS13 may ameliorate ischemic brain damage in acute stroke
physiological function
-
ADAMTS13 metalloprotease regulates the multimeric size of von Willebrand factor
physiological function
-
ADAMTS13 might regulate, after release by tubuli, the homeostasis in the local microenvironment in renal tubular epithelial cells
physiological function
-
ADAMTS13 mutations and polymorphisms are involved in congenital thrombotic thrombocytopenic purpura
physiological function
-
ADAMTS13 negatively regulates both thrombosis and inflammation. ADAMTS13 deficiency results in larger infarctions after focal cerebral ischemia in mice, but only in mice that have von Willebrand factor
physiological function
-
ADAMTS13 negatively regulates both thrombosis and inflammation. ADAMTS13 deficiency results in larger infarctions after focal cerebral ischemia in mice, but only in mice that have von Willebrand factor
physiological function
-
ADAMTS13 plays a significant role in vascular biology and thrombotic thrombocytopenic purpura
physiological function
-
ADAMTS13 regulates normal plasma van Willebrand factor multimer composition and thereby activity, through cleavage at the Tyr1605-Met1606 bond within the van Willebrand factor A2 domain
physiological function
ADAMTS13 regulates physiological von Willebrand factor size
physiological function
-
ADAMTS13 regulates the multimeric size of von Willebrand factor
physiological function
ADAMTS13 specifically cleaves plasma von Willebrand factor and regulates platelet adhesion and aggregation
physiological function
-
ADAMTS13 specifically cleaves plasma von Willebrand factor and thereby controls von Willebrand factor-mediated platelet thrombus formation. Severe deficiencies in ADAMTS13 can cause life-threatening thrombotic thrombocytopenic purpura
physiological function
-
an unusually large multimer of Von Willebrand factor and ADAMTS13 may play an important role in the onset of thrombotic microangiopathy during liver transplantation. A significant reduction of ADAMTS13 and an increase of von Willebrand factor are observed in the patients with thrombotic microangiopathy-like syndrome, overview
physiological function
-
antithrombotic properties of ADAMTS-13, complete ADAMTS-13 deficiency promotes thrombus formation and embolization in activated murine microvenule endothelium
physiological function
-
clinical relevance of ADAMTS13 activity is demonstrated by its reduction in thrombocytopenic purpura, metastasizing malignancies, liver disease, and the post-surgical state. Changes in plasma von Willebrand factor and ADAMTS13 levels are associated with left atrial remodeling in atrial fibrillation, phenotypes, overview
physiological function
-
deletion mutation in the TSP1-6 repeat domain of inherited ADAMTS13 deficiency, which is usually associated with severe forms of thrombotic thrombocytopenic purpura
physiological function
-
importance of ADAMTS13 metalloprotease in von Willebrand factor regulation and association between severe deficiency of ADAMTS13 and thrombotic thrombocytopenic purpura. However, ADAMTS13 activity levels do not always correlate with the clinical course of TTP, suggesting that other proteases, e.g. elastase or proteinase 3 expressed on leukocyte surfaces, might be important in regulating von Willebrand factor
physiological function
-
mutations in ADAMTS13 cause hereditary thrombotic thrombocytopenic purpura resulting in defective processing of von Willebrand factor that causes intravascular platelet aggregation culminating in thrombocytopenia with shistocytic anemia
physiological function
-
reactive oxygen species released by activated neutrophils have a prothrombotic effect, mediated in part by inhibition of VWF cleavage by ADAMTS13
physiological function
-
the proteolytic cleavage of von Willebrand factor by ADAMTS13 appears to be necessary to eliminate ultralarge von Willebrand factor multimers in circulation, thereby preventing the formation of platelet-rich thrombi in small arterioles and capillaries
physiological function
-
von Willebrand factor, VWF, reactivity is regulated by a VWF-cleaving protease, ADAMTS13. A temporary ADAMTS13 deficiency during liver transplantation might contribute to postoperative thrombotic complications
physiological function
-
ADAMTS-13 cleaves von Willebrand factor into smaller fragments via cleavage in the VWF A2-domain, making VWF less reactive towards platelets. ADAMTS-13 is the regulator of von Willebrand factor activity
physiological function
-
ADAMTS13 modulates von Willebrand factor platelet-tethering function by proteolysis
physiological function
-
multimeric von Willebrand factor is the mediator of both platelet adhesion to the sub-endothelium and platelet aggregation within the microvessels at high shear rates of blood flow. ADAMTS13 regulates von Willebrand factor adhesive capacity by reducing the size of von Willebrand factor multimers
physiological function
carboxyl-terminal fragments of ADAMTS13 directly inhibit platelet adhesion/aggregation on a collagen surface under arterial shear. The carboxyl-terminal fragment of ADAMTS13 is capable of inhibiting the formation and elongation of platelet-decorated ultra-large von Willebrand factor strings and the adhesion of platelets/leukocytes on endothelium in mesenteric venules after oxidative injury. The inhibitory activity on platelet aggregation and ultra-large von Willebrand factor string formation are dependent on the presence of their surface free thiols
physiological function
in Adamts13-/- mice, the transfection with homozygous mutant D187H leads to reduced ADAMTS13 secretion and activity and contributes to thrombotic thrombocytopenic purpura when these mice are triggered with recombinant human von Willebrand factor
physiological function
the distal T8-CUB2 domains markedly inhibit substrate cleavage, and binding of von Willebrand factor or monoclonal antibodies to distal ADAMTS13 domains relieves this autoinhibition. Distal T-CUB domains interact with proximal MDTCS domains. ADAMTS13 is regulated by substrate-induced allosteric activation, which may optimize von Willebrand factor cleavage under fluid shear stress in vivo
physiological function
wild-type ADAMTS13 shows 2.5fold reduced activity compared with ADAMTS13 lacking its C-terminal tail or its CUB1-2 domains. Wild-type ADAMTS13 activity is enhanced about 2.5fold by preincubation with either an anti-CUB monoclonal antibody or von Willebrand factor D4CK, the natural binding partner for the CUB domains. The isolated CUB1-2 domains bind ADAMTS13 C-terminal tails, and also inhibit activity by up to 2.5fold
physiological function
removal of the C-terminal domain of the enzyme by activated coagulation factor XI or alpha-thrombin blocks the ability of the enzyme to cleave von Willebrand factor on the endothelial cell surface, resulting in persistence of von Willebrand factor strands and causing an increase in platelet adhesion under flow conditions
additional information
-
a lower level of initial plasma ADAMTS13 activity is associated with higher risk of relapse in patients with thrombotic thrombocytopenic purpura. Also, patients with a low plasma ADAMTS13 activity and high titer inhibitor appear to have lower survival rate, overview
additional information
-
acquired deficiencies of ADAMTS13 activity, detailed overview
additional information
-
ADAMTS-13 activity gradually decreases based on the disseminated intravascular coagulation score and D-dimer levels and is correlated with the antithrombin level, representing the consumption of ADAMTS-13 during the ongoing coagulation process. No correlation between ADAMTS-13 activity and neutrophil CD64 expression
additional information
-
ADAMTS-13 activity is evaluated in a model of sepsis induced by cecum ligature and puncture in wild-type and Vwf-/- mice. In wild-type mice, cecum ligature and puncture-induced sepsis elicits a significant ADAMTS-13 decrease, and a strong negative correlation exists between von Willebrand factor, VWF, and ADAMTS-13. In Vwf-/- mice, cecum ligature and puncture also induces severe sepsis, but ADAMTS-13 is not significantly diminished
additional information
-
ADAMTS13 deficiency causes progressive decline of postischemic rCBF, with a resultant exacerbation of ischemic brain injury, role of ADAMTS13 in a transient middle cerebral arterial occlusion model of ischemia-reperfusion injury in the mouse brain using Adamts-/- mice, and comparison of effect of Adamts13 gene deletion on brain ischemia in male Adamts13-/- and wild-type mice, overview
additional information
-
ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura. Correction of ADAMTS13 deficiency by in mice in utero gene transfer of lentiviral vector encoding human ADAMTS13 genes
additional information
-
ADAMTS13 deficiency results in more and larger circulating platelet aggregates of von Willebrand factor mutants mVWF/R1306Q and mVWF/V1316M, whereas the full multimer range remains present in the mutant mice. The gain-of-function mutations of the von Willebrand factor leads to the Von Willebrand disease-type 2B, VWD-type 2B, resulting in enhanced platelet binding. Clinical manifestations include increased bleeding tendency, loss of large multimers, thrombocytopenia, and circulating platelet aggregates. The VWD-type 2B phenotype depends on the mutations and ADAMTS13, establishment of a mouse model, overview
additional information
-
ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor caused by Plasmodium falciparum and Plasmodium vivax malaria, overview
additional information
-
ADAMTS13 deficiency, due to existence of auto-antibodies against ADAMTS13, is involved in the severe disease thrombotic thrombocytopenic purpurea, TTP, characterized by thrombocytopenia, microangiopathic hemolytic anemia, and neurological and renal involvement, phenotypes, overview. Inhibition of ADAMTS13 by auto-antibodies is reversed by rituximab, overview
additional information
-
antibody formation against ADAMTS13, as ADAMTS13 inhibitor, in the course of a severe acute Dengue virus infection results in thrombotic microangiopathy. Anti-ADAMTS13 inhibitor disappears after remission of thrombotic microangiopathy and dengue resolution. No recurrence of thrombotic microangiopathy symptoms after 2-year follow-up. Thrombotic microangiopathy is a severe occlusive microvascular thrombotic syndrome characterized by profound thrombocytopenia, microangiopathic hemolytic anemia, and symptoms of organ ischemia. Thrombotic microangiopathy includes primarily two syndromes, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome
additional information
-
association between ADAMTS13 genotypes and cardiovascular events
additional information
-
association between reduced plasma ADAMTS13 antigen levels and diabetic nephropathy, with a significant positive and negative correlation between ADAMTS13 antigen and the estimated glomerular filtration rate, and von Willebrand factor/ADAMTS13 ratio, respectively, imunohistochemic analysis, overview
additional information
-
auto-antibodies, directed toward the spacer domain of ADAMTS13 involving region Y658-Y665 , cause ADAMTS13 deficiency and, as a result, acquired thrombotic thrombocytopenic purpura
additional information
-
binding of ADAMTS13 to CD36 on cell surfaces might be involved in ADAMTS13 regulation and regulation of von Willebrand cleavage
additional information
-
decreased ADAMTS13 levels in patients after living donor liver transplantation, overview
additional information
-
development of a severe von Willebrand factor/ADAMTS13 dysbalance during orthotopic liver transplantation, overview
additional information
-
genetic or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura, TTP
additional information
-
Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor, overview
additional information
-
infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Recombinant ADAMTS13 does not enhance bleeding in a hemorrhagic stroke model
additional information
-
infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Recombinant ADAMTS13 does not enhance bleeding in a hemorrhagic stroke model
additional information
-
thrombotic thrombocytopenic purpura is a potentially fatal illness caused primarily by the absence of plasma ADAMTS13 proteolytic activity, as a result of ADAMTS13 mutations or acquired autoantibodies against ADAMTS13 enzyme
additional information
-
under denaturing and fluid shear stress conditions multiple leukocyte proteases cleave von Willebrand factor predominantly in the central A2 domain. Activated neutrophils, but not normal neutrophils, retain von Willebrand factor-cleaving activity in the presence of plasma inhibitors, suggesting that leukocyte proteases may regulate von Willebrand factor function under physiologic conditions, kinetics and reaction products, overview
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ATS13_HUMAN
1427
1
153604
Swiss-Prot
Secretory Pathway (Reliability: 2)
ATS13_MOUSE
1426
1
155357
Swiss-Prot
Secretory Pathway (Reliability: 3)
A0A6J8C7I2_MYTCO
1546
0
171067
TrEMBL
Secretory Pathway (Reliability: 3)
A0A6J8ECQ0_MYTCO
616
0
69443
TrEMBL
Mitochondrion (Reliability: 5)
A0A8B6BYS9_MYTGA
562
0
63142
TrEMBL
other Location (Reliability: 1)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
150000
170000
190000
45000
x * 45000, recombinant His-tagged ADAMTS13 ancillary domains, ADAMTS13-DTCS, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
x * 45000, recombinant His-tagged ADAMTS13 ancillary domains, ADAMTS13-DTCS, SDS-PAGE
monomer
-
ADAMTS13 is a multidomain glycoprotein. It consists of numerous domains including a metalloprotease domain, a disintegrin domain, first thrombospondin type 1 repeat, i.e. TSP1, a cysteine-rich domain, and a spacer domain, schematic domain structure model of ADAMTS13, overview
additional information
ADAMTS13 is a multi-domain enzyme. In addition to the N-terminal metalloproteinase domain, the ancillary domains, including a disintegrin-like domain, a thrombospondin-1 type 1 repeat, a Cys-rich domain and a spacer domain, are required for von Willebrand factor recognition and cleavage
additional information
-
ADAMTS13 is a multi-domain enzyme. In addition to the N-terminal metalloproteinase domain, the ancillary domains, including a disintegrin-like domain, a thrombospondin-1 type 1 repeat, a Cys-rich domain and a spacer domain, are required for von Willebrand factor recognition and cleavage
additional information
-
ADAMTS13 protease consists of a signal peptide, a short propeptide, the metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat, a Cys-rich domain, a spacer domain, seven additional thrombospondin-1 repeats, and two CUB domains
additional information
-
ADAMTS13-DTCS, residues 287-685, an exosite-containing ADAMTS13 fragment, structures reveal folding similarities between the disintegrin-like domain and the N-terminal portion of the cysteine-rich domain. The spacer domain forms a globular functional unit with a 10-stranded-sandwich fold that has multiple interaction sites with the cysteine-rich domain. The MDTCS domains are conserved among ADAMTS family proteins
additional information
-
epitope mapping of anti-ADAMTS13 immunoglobulin G from patients with thrombotic thrombocytopenic purpura and sequence alignment of the ADAMTS13 spacer domains of human, mouse, and zebrafish
additional information
-
the metalloprotease domain is required for activity but not sufficient, the spacer domain is indispensable for activity, and the Cys-rich domain is also involved in activity. Also an intracellular disulfide bond is essential for catalytic activity. ADAMTS13 multidomain structure, overview
additional information
-
the multidomain ADAMTS13 contains the metalloprotease, the disintegrin, the TSP1-1, the cysteine-rich, the spacer, the TSP1-2, TSP1-3, TSP1-5, TSP1-6, TSP1-7, TSP1-8, CUB-1, and CUB-2 domains
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
binding site for alpha-mannosyl residue, 10 potential N-glycosylation sites, Asn-Xaa-Thr/Ser
glycoprotein
N-glycosylation is necessary for efficient secretion of ADAMTS13, while conversion of the N-glycans from oligomannose to complex type in the Golgi complex enhances the proteolytic activity of the protease toward von Willebrand factor multimers. After its secretion, ADAMTS13 does not require N-glycans for its von Willebrand factor cleaving activity
glycoprotein
the ADAMTS13 ancillary domains, ADAMTS13-DTCS, contain four potential N-glycosylation sites
proteolytic modification
made as a zymogen, requires proteolytic activation, possibly intracellularly by furin, cleavage of residues 1-74
proteolytic modification
-
propeptide is very short and poorly conserved, dispensable for protein folding, is cleaved off by furin after export from the endoplasmic reticulum, the pro-enzyme form is fully active
proteolytic modification
-
the pro-peptide is removed during self-activation, which is not required for full enzyme activity
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in electron microscopy, wild-type ADAMTS13 adopts a closed conformation, gain-of-function mutant R568K/F592Y/R660K/Y661F/Y665F shows a more open conformation
purified recombinant detagged ADAMTS13-DTCS, residues 287-685, an non-catalytic von Willebrand factor-exosite-containing ADAMTS13 fragment, sitting drop vapor diffusion method, mixing of 500 nl of protein solution and 500 nl reservoir solution containing 26% w/v PEG1500, 100 mM MES, pH 6.0, supplemented with 200 nl of 40% w/w pentaerythritol ethoxylate, equilibration for several days at 20°C. Os-derivative crystals by soaking native crystals in reservoir solution supplemented with 1 mM OsCl3 and 20% glycerol for several hours, X-ray diffraction structure determination and analysis at 2.6 A and 2.8 A resolution resulting in two crystal structures
-
recombinant His-tagged ADAMTS13 ancillary domains, residues 287-685, sitting-drop vapour-diffusion method, mixing of 100 nl protein solution, containing about 20 mg/ml protein, with an equal amount of reservoir solution, containing 26% w/v PEG 1500, 100 mM MES, pH 6.0, equilibration against 0.1 ml of reservoir solution, at 20°C, for 24 h, crystals are soaked in a solution containing 20% glycerol, 26% PEG 1500, 100 mM MES, pH 6.0, for cryoprotection, X-ray diffraction structure determination and analysis at 2.6-2.8 A resolution, labeling with heavy-atom derivatives
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
568K/F592Y/R660K/Y661F/Y665F
-
the mutant shows enhanced proteolytic activity compared to the wild type enzyme
A900V
C508Y
C977W
-
deletion of 6 nucleotides GTGCCC at position 2930-2935, i.e. c.2930_2935del GTGCCC, in exon 23, leading to the replacement of Cys977 residue by a Trp
D187A
D187H
mutation identified in a patient with pregnancy-onset thrombotic thrombocytopenic purpura. Mutation is located in the high affinity Ca2+-binding site in the metalloprotease domain of ADAMTS13. The homozygous mutation down-regulates ADAMTS13 activity in vitro. Impaired proteolytic activity is linked to unstable Ca2+ binding. In addition, the D187H mutation affects protein secretion in vitro
D252N
-
the ADAMTS13 VR2 single-point mutant is secreted as the wild type enzyme
D330A
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
D340A
-
site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
D343A
-
site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
D500E
-
point mutation in the RGD cysteine-rich domain, unaltered activity compared to the wild-type enzyme
E184A
E184A/L185A/D187A/R190A
-
the proteolytic function of the mutant is severely affected
E184A/L185A/D187A/R190A/Q191A/V192N/R193A
-
the mutant has abolished activity against von Willebrand factor 115
E212A
-
site-directed mutagenesis of a Ca2+ binding site residue, the kinetic dissociation constant of ADAMTS13 for Ca2+ is dramatically reduced compared to the wild-type enzyme, Vmax of the mutant is also reduced by 75% compared to the wild-type
E663A
E664A
G1239V
G662A
L350G
-
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
L351G
-
site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
P475S
P618A
Q333A
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
Q448E
R190A
-
the mutant shows 2fold reduced catalytic efficiency against von Willebrand factor 115 compared to the wild type enzyme
R193A
-
the mutant shows 4fold reduced catalytic efficiency against von Willebrand factor 115 compared to the wild type enzyme
R257A
-
the ADAMTS13 VR2 single-point mutant is secreted as the wild type enzyme
R268P
R349A
-
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme, the mutant enzyme shows increased activity with the mutant D1614A von Willebrand factor115 substrate compared to the wild-type enzyme
R568K/F592Y/R660K/Y661F/Y665F
gain-of-function ADAMTS13 spacer domain variant, about 2.5fold more active than wild-type ADAMTS13, but cannot be further activated by anti-CUB monoclonal antibody or von Willebrand factor D4CK and is unable to bind or to be inhibited by the CUB1-2 domains
R659A
R660A
R660A/Y661A/Y665A
-
site-directed mutagenesis, the ADAMTS13 variant, i.e. ADAMTS13-RYY, shows a 12fold reduced catalytic efficiency arising from over 25fold reduced substrate binding
R7W
S119A
-
site-directed mutagensis, mutant S119A has properties similar to natural mutant S119F
S119F
S119F/Q448E
-
naturally occuring mutation in the ADAMTS13 metalloprotease domain. The mutant is expressed normally, but shows markedly impaired secretion
T260A
-
the ADAMTS13 VR2 single-point mutant is secreted as the wild type enzyme
V352G
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
V88M
W390A
the mutant has impaired binding affinity to its substrate von Willebrand factor. The mutation retards the enzyme's secretion, leading to its deposition in endoplasmic reticulum. Compared with the wild type enzyme, the mutant also has a decreased cleavage activity for multimeric von Willebrand factor under both static and shear stress conditions
Y661A
additional information
A900V
-
naturally occuring C2699T polymorphism in patients with coronary artery disease and preserved left ventricular function
C508Y
-
naturally occuring mutant, no secretion of the enzyme to the plasma, possible defects in secretion pathway, or protein folding and stability
D187A
-
site-directed mutagenesis of a Ca2+ binding site residue, the kinetic dissociation constant of ADAMTS13 for Ca2+ is dramatically reduced compared to the wild-type enzyme, Vmax of the mutant is also reduced by 75%, and Kcat/Km 13fold, compared to the wild-type
D187A
-
the mutant shows 10fold reduced catalytic efficiency against von Willebrand factor 115 compared to the wild type enzyme
E184A
-
site-directed mutagenesis of a Ca2+ binding site residue, the kinetic dissociation constant of ADAMTS13 for Ca2+ is dramatically reduced compared to the wild-type enzyme
E663A
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme with substrate VWF73 peptide
E664A
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme with substrate VWF73 peptide
G1239V
-
mutation leads to a secretion defect causing intracellular accumulation of the protease
G662A
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme with substrate VWF73 peptide
P475S
-
the ADAMTS13 mutant shows similar expression but reduced activity compared to the wild-type enzyme, and minimal von Willebrand factor-induced changes in conformation
P475S
-
the common naturally occuring polymorphsim is not involved in ADAMTS13 inhibition in malaria patients
P618A
-
naturally occuring C1852G polymorphism in patients with coronary artery disease and preserved left ventricular function
P618A
-
naturally occuring mutation of ADAMTS13 involved in inherited thrombotic thrombocytopenic purpura
Q448E
-
naturally occuring C1342G polymorphism in patients with coronary artery disease and preserved left ventricular function
Q448E
-
naturally occuring mutation of ADAMTS13 involved in inherited thrombotic thrombocytopenic purpura
R268P
-
naturally occuring mutant, no secretion of the enzyme to the plasma, possible defects in secretion pathway, or protein folding and stability
R659A
-
site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme with substrate VWF73 peptide
R660A
-
site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme with substrate VWF73 peptide
R7W
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naturally occuring mutation of ADAMTS13 involved in inherited thrombotic thrombocytopenic purpura
S119F
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a naturally occuring mutation in the ADAMTS13 metalloprotease domain that leads to distorted kinetics and to the loss of the H-bond with conserved residue W262, the mutation is involved in development of hereditary thrombotic thrombocytopenic purpura due to reduced ADAMTS13 activity, overview. Secreted S119F is active toward multimeric von Willebrand factor and FRETSVWF73 but with abnormal kinetics. The mutant is expressed normally, but shows markedly impaired secretion
V88M
-
mutation leads to a defect of secretion of the protease associated with a reduction of enzymatic activity
Y661A
-
site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme with substrate VWF73 peptide
additional information
-
construction of 13 sequential C-terminal truncated mutants, mutants lacking the the cysteine-rich and spacer domain show dramatically reduced or no activity, the other mutants retain their activity, overview
additional information
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construction of an enzyme truncated after the metalloprotease domain, which is inactive, addition of the spacer region can restore activity, overview
additional information
-
natural mutant is cleaved at peptide bond Tyr1605-Met1606
additional information
-
Q449stop mutant is efficiently secreted, has a MW of 54 kDa, and shows no activity, detection of naturally occuring mutations in a Japanese family with thrombotic thrombocytopenic pupura, overview
additional information
-
introduction of polymorphisms R7W, Q448E, and A732V have no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V/P618A combination strongly reduce ADAMTS13-specific activity and antigen levels. R7W and Q448E are positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither can rescue the severely reduced specific activity conferred by P618A. In the context of R133W, polymorphisms R7W and Q448E enhance the detrimental effect of the missense mutation and lead to undetectable enzyme activity
additional information
-
deletion mutation C365DEL and a point mutation R1060W severely impair ADAMTS-13 synthesis and decrease of von Willebrand cleaving activity
additional information
-
ability of systemically administered adenovirus encoding human ADAMTS13 to restore the deficient protein in the circulation of Adamts13-/- mice, derived from B/129 wild-type mice. Injection of the adenovirus efficiently transduces the liver, kidney, lung, heart and spleen, resulting in the secretion of ADAMTS13 into plasma, especially from lung and liver, not from brain, overview
additional information
-
analysis of ADAMTS13 mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura, wide spectrum of clinical phenotype in congenital thrombotic thrombocytopenic purpura, overview
additional information
-
construction of a self-inactivating lentiviral vector encoding human full-length ADAMTS13 and a variant truncated after the spacer domain, MDTCS. In utero gene transfer of lentiviral vector encoding ADAMTS13 genes by injection at embryonic days 8 and 14 resulting in detectable plasma proteolytic activity. The mice expressing ADAMTS13 and MDTCS exhibit reduced sizes of von Willebrand factor compared to the Adamts13-/- mice, they show increased survival rates and functional enzyme activity in plasma, overview. The expressed human ADAMTS13 and MDTCS offer systemic protection against arterial thrombosis
additional information
-
construction of ADAMTS13 truncated mutants, MDTCS and del(TSP5-CUB), and analysis of their binding with different C-terminal domain VWF fragments, overview
additional information
-
construction of disintegrin domain mutants by site-directed mutagenesis, that exhibit dramatically reduced activity toward the von Willebrand factor fragment VWF115, comprising amino acid residues 1554-1668 of von Willebrand factor. The isolated metalloprotease domain of ADAMTS13 alone is ineffective in cleaving, but if the various noncatalytic domains are incrementally added back, proteolytic activity is gradually restored
additional information
-
construction of truncated DAMTS13 mutants MP-Dis and MP, which have a molecular weight of 30 kDa and 40 kDa, respectively
additional information
-
deletion of amino acid residues Arg659-Glu664 from the ADAMTS13 spacer domain by site-directed mutagenesis results in dramatically reduced proteolytic activity toward von Willebrand factor73 peptides, guanidine-HCl denatured von Willebrand factor, and native von Willebrand factor under fluid shear stress, as well as ultralarge von Willebrand factor on endothelial cells
additional information
-
generation of structure-based mutants of ADAMTS13-MDTCS residues 75685 fragment. The MDTCS domains are conserved among ADAMTS family proteins
additional information
-
identification of a deletion of two amino acids Ala978 and Arg979, i.e. p.C977W+p.A978_R979del, in the TSP1-6 repeat domain of ADAMTS13 in a family with inherited thrombotic thrombocytopenic purpura. Three common ADAMTS13 intragenic SNPs p.R7W, p.Q448E and p.P618A are also identified in heterozygous state in paternal alleles (I:2) and also in II:5 and II:8.
additional information
replacement of signal sequence and prosequence with the mouse Nid1 signal sequence dramatically increases the secretion of ADAMTS13-DTCS into the medium
additional information
-
replacement of signal sequence and prosequence with the mouse Nid1 signal sequence dramatically increases the secretion of ADAMTS13-DTCS into the medium
additional information
-
generation of a congenic mouse model expressing the C-terminally truncated form of ADAMTS13 on 129/Sv genetic background, presence of IAP insertion in the Adamts13 gene of the congenic Adamts13S/S mice by PCR, and detection an IAP chimeric transcript by Northern blotting of RNA from liver, overview. The distal C-terminally truncated form of mouseADAMTS13 does not completely lose the activity. In vivo thrombus growth is accelerated in Adamts13S/S mice, overview
additional information
-
plasma ADAMTS13 proteolytic activity on average can be restored in Adamts13-/- mice to approximately 25% of wild-type level by autologous transplantation of hematopoietic progenitor cells transduced ex vivo with a self-inactivating lentiviral vector encoding a full-length murine Adamts13 and an enhanced GFP reporter gene
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.1 - 8.8
-
the activity of purified pADAMTS13 is stable and relatively constant at pH ranges between pH 6.1 and 8.8 for 18 h storage at 4°C. However, ADAMTS13 activity is almost totally lost below pH 3.1
719761
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 37
-
the enzyme is stable at room temperature for up to 24 h irrespective of the presence of citrate (0.38% (w/v)). However, at 37°C, citrate causes a time-dependent activity decrease
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
no enzyme activity decrease is seen in heparinized plasma, but the addition of citrate causes enzyme instability at 37°C
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
A10-agarose column chromatography, HiTrap DEAE column chromatography, and Superdex 200 gel filtration
-
recombinant ADAMTS-13 from HEK293 cells by Zn2+-agarose affinity and anion exchange chromatography to homogeneity
-
recombinant His-tagged ADAMTS13 ancillary domains, ADAMTS13-DTCS, consisting of residues 287-685, from CHO Lec cells by nickel affinity and cation exchange chromatography
recombinant His-tagged ADAMTS13 from HEK-293 cells by anion exchange chromatography, Ni affinity chromatography, and gel filtration
-
recombinant structure-based mutants of ADAMTS13-MDTCS residues 75-685 fragment with a C-terminal tobacco etch virus proteinase cleavage site followed by tandem His-tag sequences from CHO Lec 3.2.8.1 cells by nickel affinity chromatography and gel filtration
-
recombinant wild-type ADAMTS13 with a C-terminal Myc/His tag from HEK293 cells, and recombinant His-tagged truncated DAMTS13 mutants MP-Dis and MP by nickel affinity chromatography and gel filtration
-
recombinant wild-type and mutant ADAMTS13 from HEK-293 cells by nickel affinity chromatography
-
recombinant wild-type and mutant ADAMTS13s with a C-terminal Myc/His tag expressed from HEK-293 cells by nickel affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
ADAMTS13 DNA and amino acid sequence determination and analysis of wild-type and mutant enzymes, genotyping and expression analysis in HEK-293 cells, overview
-
DNA sequence determination and analysis, transient expression of wild-type and mutants as FLAG-tagged enzymes in HeLa cells
-
DNA sequence determination of natural genetic variants, heterozygous polymorphism at Tyr/Cys1584 and other, overview
-
expression in HEK-293 cell
expression of a series of partial deletions in the A2 domain flanked with N- and C-terminal tags in Escherichia coli
-
expression of FLAG-tagged ADAMTS13 in HEK-293 cells, co-expression with thrombospondin1
expression of structure-based mutants of ADAMTS13-MDTCS residues 75-685 fragment with a C-terminal tobacco etch virus proteinase cleavage site followed by tandem His-tag sequences in CHO Lec 3.2.8.1 cells. Transient expression of His-tagged mutant ADAMTS13-MDTCS domains using a cytomegalovirus promoter-driven expression vector in HeLa cells
-
expression of wild-type ADAMTS13 with a C-terminal Myc/His tag in HEK293 cells, transient expression of His-tagged truncated DAMTS13 mutants MP-Dis and MP and point mutants in HEK-293T cells
-
expression of wild-type and mutant ADAMTS13s with a C-terminal Myc/His tag expressed in HEK-293 cells
-
expression of wild-type and mutant enzyme forms in HEK-293 cells and CHO cells
-
gene Adamts13, DNA and amino acid sequence determination and analysis, expression of truncated ADAMTS13 in 129/Sv transgenic mice
-
gene Adamts13, DNA and amino acid sequence determination, construction of self-inactivated lentiviral vector, and expression of functional His-tagged ADAMTS13 cDNA in COS-7 cells
-
gene ADMTS13 and mutant variant truncated after the spacer domain, MDTCS, expression in transgenic mice
-
stable expression of His-tagged ADAMTS13 ancillary domains, ADAMTS13-DTCS, consisting of residues 287-685, in CHO Lec cells
transient expression in HeLa cells, in HepG2 cells, in RFL6 cells, and in COS-1 cells, highest expression level is obtained in HeLa cells
-
transient expression of C-terminally tagged enzyme in COS-7 cells or expression in a Sf9 cells/baculovirus expression system, tagged with His6 or V5 epitopes
-
transient expression of wild-type and mutants in HeLa cells as FLAG-tagged proteins
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme activity is significantly higher in men with acute human immunodeficiency virus infection than in uninfected controls and in both acute and chronic untreated HIV infection relative to chronic treated infection
-
plasma enzyme activity in aneurysmal subarachnoid haemorrhage patients is significantly lower than that in healthy subjects
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a 77-amino acid flow cytometry substrate to measure ADAMTS13 activity. Substrate is suitable for microsphere-cytometer based assays in the milieu of human blood plasma. It contains the partial A2-domain of von Willebrand factor (VWF amino acids 1594-1670) that is mutated to include a single primary amine at the N-terminus and free cysteines at the C-terminus. Substrate is bound to streptavidin-bearing microspheres with varyable polyethylene glycol spacer lengths. Recombinant ADAMTS13 activity can be quantified using substrates with all varyable polyethylene glycol repeat-lengths, but only a construct with the longer 77 PEG-unit can quantify proteolysis in blood plasma. Plasma ADAMTS13 down to 5% of normal levels can be detected within 30 min. Enzyme catalytic activity is tuned by varying buffer calcium, with lower divalent ion concentrations enhancing cleavage
diagnostics
drug development
-
inhibitory anti-ADAMTS 13 antibodies, measurement and clinical application, overview
medicine
diagnostics
-
ADAMTS-13 may serve as a diagnostic and prognostic marker of disseminated intravascular coagulation. Patients with a low activity of ADAMTS-13 have a poor survival rate compared to patients with a high activity of ADAMTS-13
diagnostics
-
Potential role of ADAMTS13 as a diagnostic and prognostic marker of disseminated intravascular coagulopathy. ADAMTS13 and the activity of von Willebrand factor are also a marker for development of multiple organ dysfucntion in infectious and non-infectious systemic inflammatory response syndrome
diagnostics
-
role for clinical testing of plasma ADAMTS13 activity and inhibitors in care of thrombotic thrombocytopenic purpura patients, overview
diagnostics
-
role of ADAMTS 13 assays in diagnosis and prognosis of thrombotic thrombocytopenic purpura, TTP, overview
diagnostics
-
value of ADAMTS13 activity and inhibitor in the postmortem diagnosis of thrombotic thrombocytopenic purpura, overview
medicine
-
analysis of vWF protease and vWF multimeric distribution are valuable tools in making the distinction between bone marrow transplant-associated thrombotid microangiopathy and thrombotic thrombocytopenic pupura
medicine
-
ADAMTS-13 is deficient in congenital thrombotic thrombocytopenic purpura and inhibited in aquired thrombotic thrombocytopenic purpura. The availability of recombinant ADAMTS-13 raises the prospect of developing a recombinant substitution therapy to improve thrombotic thrombocytopenic purpura treatment and allows present diagnostic assays to be simplified
medicine
-
assay using recombinant or synthetic substrates (high-throughput methods) will contribute significantly to the accurate diagnosis of microangiopathies, ultimately leading to improved treatment of these diseases. These assays may also help clarify the role of ADAMTS13 in thrombotic disorders including disseminated intravascular coagulation, stroke, and myocardial infarction
medicine
-
description of a simple procedure to analyse the kinetics of von Willebrand factor proteolysis that is suitable for routine diagnostic use
medicine
in order to develop new strategies for improving the diagnosis and treatment of thrombotic thrombocytopenic purpura, this study systemically analyzed a series of ADAMTS13 mutant proteins to identify variant forms that are proteolytically active and yet resistant to suppression by inhibitory antibodies. A deficiency ofADAMTS13, due to mutations in the ADAMTS13 gene or the presence of antibodies that inhibit the activity of the protease,causes thrombotic thrombocytopenic purpura. Plasma therapy, the conventional therapy for TTP, may cause serious adverse reactions and is ineffective in some patients
medicine
-
VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13. VWF73 could be a powerful tool to establish clinical enzymatic assays. It may contribute to improve the prognosis and prevention of thrombotic thrombocytopenic purpurea
medicine
-
ADAMTS13 deficiency and the resultant increase in von Willebrand factor adhesion activity may be clinically significant for association with the severity of thrombocytopenia and clinical prognosis in sepsis, sickle cell disease, and and increased risk for stroke
medicine
levels of ADAMTS13 are lower and levels of Von Willebrand Factor are higher in young patients with cardiovascular disease compared to healthy individuals. Individuals with low levels of ADAMTS13 had five times more risk on cardiovascular disease than subjects with normal levels of ADAMTS13. The relationship is strongest in the subgroup of patients with coronary heart disease. This may be of importance for identifying individuals who are prone to have a cardiovascular event
medicine
-
correction of ADAMTS13 deficiency by in utero gene transfer of lentiviral vector encoding ADAMTS13 genes
medicine
-
infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Thus, recombinant ADAMTS13 can be considered as a therapeutic agent for prevention and/or treatment of stroke. Recombinant ADAMTS13 does not enhance bleeding in a hemorrhagic stroke model
medicine
ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura. Cyclosporin A, an inhibitor of cyclophilin B, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. Cyclophilin B and ADAMTS13 show a direct, functional interaction
medicine
ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura. Cyclosporin A, an inhibitor of cyclophilin B, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. Cyclophilin B and ADAMTS13 show a direct, functional interaction
medicine
exposure of ADAMTS13 to activated human neutrophils results in oxidation of residues Met249, Met331, and Met496 in important functional domains ofADAMTS13. ADAMTS13 treated with either neutrophil elastase or plasmin is inhibited to a lesser extent, especially in the presence of plasma.
medicine
increased plasma enzyme activity after 1 year entecavir treatment is associated with a higher seroconversion, and can be used surrogate of hepatitis B virus e antigen seroconversion in chronic hepatitis B patients during 5-year entecavir treatment
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Release 2023.1 (January 2023)
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