3.4.24.87: ADAMTS13 endopeptidase
This is an abbreviated version!
For detailed information about ADAMTS13 endopeptidase, go to the full flat file.
Word Map on EC 3.4.24.87
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3.4.24.87
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thrombotic
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thrombocytopenic
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purpura
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ttp
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platelet
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multimers
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hemolytic
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anemia
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endothelial
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metalloproteinase
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autoantibody
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microangiopathic
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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
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coagulation
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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
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relapsing
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plasmapheresis
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ultra-large
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hemostat
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disintegrin-like
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microcirculation
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vwf:ag
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coombs
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plasmic
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microthrombi
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shiga
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hellp
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collagen-binding
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antiphospholipid
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microthrombosis
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d-dimers
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fviii
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prothrombotic
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apheresis
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hemolytic-uremic
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ristocetin
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eculizumab
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medicine
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oklahoma
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analysis
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drug development
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diagnostics
- 3.4.24.87
-
thrombotic
-
thrombocytopenic
- purpura
- ttp
- platelet
- multimers
-
hemolytic
- anemia
- endothelial
- metalloproteinase
- autoantibody
-
microangiopathic
- rituximab
-
remission
-
uremic
-
microvascular
-
relapse
-
life-threatening
-
shear
-
idiopathic
- coagulation
- autoimmune
-
thrombi
-
bleeding
-
hemostasis
-
schistocytes
-
intravascular
-
relapsing
-
plasmapheresis
-
ultra-large
-
hemostat
-
disintegrin-like
-
microcirculation
-
vwf:ag
-
coombs
- plasmic
-
microthrombi
-
shiga
-
hellp
-
collagen-binding
-
antiphospholipid
-
microthrombosis
-
d-dimers
- fviii
-
prothrombotic
-
apheresis
-
hemolytic-uremic
- ristocetin
- eculizumab
- medicine
-
oklahoma
- analysis
- drug development
- diagnostics
Reaction
The enzyme cleaves the von Willebrand factor at bond Tyr842-/-Met843 within the A2 domain =
Synonyms
a disintegrin and metalloprotease with thrombospondin motifs 13, a disintegrin and metalloprotease with thrombospondin type 1 repeats 13, a disintegrin and metalloprotease with thrombospondin-13, a disintegrin and metalloproteinase with a thrombonspondin type 1 motif member 13, a disintegrin and metalloproteinase with a thrombospondin motif repeats 13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, a disintegrin-like and metalloprotease with thrombospondin type I repeats – 13, a disintegrin-like and metalloprotease with thrombospondin type-1 motifs 13, a disintegrin-like and metalloproteinase domain with thrombospondin type I motifs 13, a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13, a disintegrin-like domain and metalloprotease with thrombospondin type I motif, a thrombospondin type 1 motif, member 13, ADAMTS 13, ADAMTS VWF cleaving metalloprotease, ADAMTS-13, ADAMTS13, ADAMTS13 metalloprotease, M12.241, metalloprotease ADAMTS-13, More, plasma metalloprotease ADAMTS13, plasma von Willebrand factor cleaving activity, Upshaw factor, van Willebrand factor processing activity, von Willebrand cleavage protease, von Willebrand cleavaging protease, von Willebrand factor cleaving protease, von Willebrand factor specific cleaving protease, von Willebrand factor-cleaving metalloprotease, von Willebrand factor-cleaving protease, von Willebrand factor-cleaving proteinase, von-Willebrand factor cleaving protease, von-Willebrand factor degrading protease, von-Willebrand-factor-cleaving protease, VWF cleaving metalloprotease, VWF cleaving protease, vWF protease, VWF-cleaving metalloprotease, vWF-cleaving protease, VWF-CP, vWF-degrading protease, VWFCP, xWF-CP
ECTree
3.4.24.87 ADAMTS13 endopeptidaseAdvanced search results
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results (Engineering
Engineering on EC 3.4.24.87 - ADAMTS13 endopeptidase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
568K/F592Y/R660K/Y661F/Y665F
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the mutant shows enhanced proteolytic activity compared to the wild type enzyme
A900V
C508Y
C977W
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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
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the ADAMTS13 VR2 single-point mutant is secreted as the wild type enzyme
D330A
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
D340A
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
D343A
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
D500E
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point mutation in the RGD cysteine-rich domain, unaltered activity compared to the wild-type enzyme
E184A
E184A/L185A/D187A/R190A
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the proteolytic function of the mutant is severely affected
E184A/L185A/D187A/R190A/Q191A/V192N/R193A
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the mutant has abolished activity against von Willebrand factor 115
E212A
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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
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site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
L351G
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
P475S
P618A
Q333A
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
Q448E
R190A
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the mutant shows 2fold reduced catalytic efficiency against von Willebrand factor 115 compared to the wild type enzyme
R193A
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the mutant shows 4fold reduced catalytic efficiency against von Willebrand factor 115 compared to the wild type enzyme
R257A
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the ADAMTS13 VR2 single-point mutant is secreted as the wild type enzyme
R268P
R349A
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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
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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
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site-directed mutagensis, mutant S119A has properties similar to natural mutant S119F
S119F
S119F/Q448E
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naturally occuring mutation in the ADAMTS13 metalloprotease domain. The mutant is expressed normally, but shows markedly impaired secretion
T260A
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the ADAMTS13 VR2 single-point mutant is secreted as the wild type enzyme
V352G
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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
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naturally occuring C2699T polymorphism in patients with coronary artery disease and preserved left ventricular function
C508Y
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naturally occuring mutant, no secretion of the enzyme to the plasma, possible defects in secretion pathway, or protein folding and stability
D187A
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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
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the mutant shows 10fold reduced catalytic efficiency against von Willebrand factor 115 compared to the wild type enzyme
E184A
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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
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme with substrate VWF73 peptide
E664A
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme with substrate VWF73 peptide
G1239V
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mutation leads to a secretion defect causing intracellular accumulation of the protease
G662A
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme with substrate VWF73 peptide
P475S
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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
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the common naturally occuring polymorphsim is not involved in ADAMTS13 inhibition in malaria patients
P618A
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naturally occuring C1852G polymorphism in patients with coronary artery disease and preserved left ventricular function
P618A
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naturally occuring mutation of ADAMTS13 involved in inherited thrombotic thrombocytopenic purpura
Q448E
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naturally occuring C1342G polymorphism in patients with coronary artery disease and preserved left ventricular function
Q448E
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naturally occuring mutation of ADAMTS13 involved in inherited thrombotic thrombocytopenic purpura
R268P
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naturally occuring mutant, no secretion of the enzyme to the plasma, possible defects in secretion pathway, or protein folding and stability
R659A
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site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme with substrate VWF73 peptide
R660A
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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
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mutation leads to a defect of secretion of the protease associated with a reduction of enzymatic activity
Y661A
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site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme with substrate VWF73 peptide
additional information
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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
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natural mutant is cleaved at peptide bond Tyr1605-Met1606
additional information
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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
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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
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deletion mutation C365DEL and a point mutation R1060W severely impair ADAMTS-13 synthesis and decrease of von Willebrand cleaving activity
additional information
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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
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analysis of ADAMTS13 mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura, wide spectrum of clinical phenotype in congenital thrombotic thrombocytopenic purpura, overview
additional information
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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
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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
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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
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construction of truncated DAMTS13 mutants MP-Dis and MP, which have a molecular weight of 30 kDa and 40 kDa, respectively
additional information
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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
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generation of structure-based mutants of ADAMTS13-MDTCS residues 75–685 fragment. The MDTCS domains are conserved among ADAMTS family proteins
additional information
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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
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replacement of signal sequence and prosequence with the mouse Nid1 signal sequence dramatically increases the secretion of ADAMTS13-DTCS into the medium
additional information
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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
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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
