Information on EC 3.4.21.38 - coagulation factor XIIa

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.38
-
RECOMMENDED NAME
GeneOntology No.
coagulation factor XIIa
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
selective cleavage of Arg-/-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
endopeptidase
-
CAS REGISTRY NUMBER
COMMENTARY hide
75216-42-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
benzoyl arginine ethyl ester + H2O
benzoyl-Arg + ethanol
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ala-Arg-SCH2C6H5 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ala-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ala-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ala-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Asn-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Asn-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Glu-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Glu-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Gly-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Lys-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Lys-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Lys-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
best substrate
-
-
?
benzyloxycarbonyl-Met-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Phe-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Phe-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Pro-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Pro-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Pro-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ser-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ser-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Ser-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Thr-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Val-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
Biophen CS11-22 + H2O
?
show the reaction diagram
-
-
-
-
?
Boc-Gln-Gly-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
fluorogenic substrate
-
-
?
C1 esterase + H2O
activated C1 esterase
show the reaction diagram
-
-
-
-
?
D-Pro-Phe-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
factor VII + H2O
?
show the reaction diagram
-
enzyme is involved in the blood coagulation cascade
-
-
?
factor VII + H2O
factor VIIa
show the reaction diagram
factor XI + H2O
?
show the reaction diagram
-
enzyme is involved in the blood coagulation cascade
-
-
?
factor XI + H2O
factor XIa
show the reaction diagram
factor XI + H2O
factor XIa + ?
show the reaction diagram
N-benzoyl-L-Phe-L-Val-L-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-Ile-Glu-OCH-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-Ile-Glu-OH-Gly-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Pefachrome + H2O
?
show the reaction diagram
-
-
-
-
?
plasminogen proactivator + H2O
?
show the reaction diagram
-
-
-
-
?
prekallikrein + H2O
?
show the reaction diagram
prekallikrein + H2O
activated prekallikrein
show the reaction diagram
-
-
-
-
?
prekallikrein + H2O
activated prekallikrein + ?
show the reaction diagram
-
-
-
-
?
prekallikrein + H2O
kallikrein + kallikrein prepeptide
show the reaction diagram
prekallikrein + H2O
kallikrein + kallikrein propeptide
show the reaction diagram
-
-
-
-
?
Pro-Phe-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Arg-SCH2C6H5 + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Arg-SCH2CH(CH3)2 + H2O
?
show the reaction diagram
-
-
-
-
?
tosyl arginine methyl ester + H2O
tosyl-Arg + methanol
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
factor VII + H2O
?
show the reaction diagram
-
enzyme is involved in the blood coagulation cascade
-
-
?
factor XI + H2O
?
show the reaction diagram
-
enzyme is involved in the blood coagulation cascade
-
-
?
factor XI + H2O
factor XIa + ?
show the reaction diagram
prekallikrein + H2O
kallikrein + kallikrein prepeptide
show the reaction diagram
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Ala-Phe-Arg-chloromethylketone
-
-
alpha2-Macroglobulin
-
-
-
antithrombin III
-
C1 esterase inhibitor
-
C1 inhibitor
-
-
-
corn trypsin inhibitor
-
D-Pro-Phe-Arg-chloromethyl ketone
dansyl-Glu-Gly-Arg-chloromethylketone
-
-
diisopropyl phosphofluoridate
histidine-rich glycoprotein
-
inhibitor of autoactivation, inhibitor of activation of factor XI
-
Ir-CPI
-
Lima bean trypsin inhibitor
-
-
-
PCK
-
factor XIIa inhibitor, protects mice from ischemic brain injury
Phe-Phe-Arg-chloromethylketone
-
-
Phe-Pro-Arg-chloromethylketone
-
-
phenyl methylsulfonyl fluoride
-
-
Pro-Phe-Arg chloromethylketone
Pumpkin seed inhibitor
-
the inhibitor is isolated from Cucurbita maxima, minimum MW is 3268 Da
-
rHA-infestin-4
serine protease inhibitor isolated from Triatoma infestans
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Dextran
-
dextran-mediated activation and autoactivation
ellagic acid
-
activation of factor XII by negatively charged agents, e.g. ellagic acid, is not necessarily accompanied by molecular scission
High molecular weight kininogen
-
-
-
Kallikrein
-
mediates activation of the zymogen FXII
-
kaolin
-
long-chain polyphosphate
-
-
-
plasma kallikrein
-
plasma prekallikrein
-
-
-
streptokinase SK
-
enzyme activity in plasma increases 2fold over 60 min in patients treated with fibrinolytic agents, tissue plasminogen activator t-PA or with streptokinase SK
-
TGFbeta
-
treatment of human lung fibroblasts with TGF-beta1 results in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3
-
tissue plasminogen activator t-PA
-
enzyme activity in plasma increases 2fold over 60 min in patients treated with fibrinolytic agents, tissue plasminogen activator t-PA or with streptokinase SK
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012
benzyloxycarbonyl-Ala-Arg-SCH2C6H5
-
-
0.034
benzyloxycarbonyl-Ala-Arg-SCH2CH(CH3)2
-
-
3.9
benzyloxycarbonyl-Ala-Gly-Arg-4-nitroanilide
-
-
1.5
benzyloxycarbonyl-Ala-Phe-Arg-4-nitroanilide
-
-
0.103
benzyloxycarbonyl-Arg-SCH2CH(CH3)2
-
-
2.7
benzyloxycarbonyl-Asn-Gly-Arg-4-nitroanilide
-
-
0.66
benzyloxycarbonyl-Asn-Phe-Arg-4-nitroanilide
-
-
0.15
benzyloxycarbonyl-Glu-Arg-SCH2CH(CH3)2
-
-
0.036
benzyloxycarbonyl-Gly-Arg-SCH2CH(CH3)2
-
-
0.054
benzyloxycarbonyl-Lys-Arg-SCH2CH(CH3)2
-
-
0.7
benzyloxycarbonyl-Lys-Gly-Arg-4-nitroanilide
-
-
0.16
benzyloxycarbonyl-Lys-Phe-Arg-4-nitroanilide
-
-
0.019
benzyloxycarbonyl-Met-Arg-SCH2CH(CH3)2
-
-
0.006
benzyloxycarbonyl-Phe-Arg-SCH2CH(CH3)2
-
-
8.2
benzyloxycarbonyl-Phe-Gly-Arg-4-nitroanilide
-
-
0.036
benzyloxycarbonyl-Pro-Arg-SCH2CH(CH3)2
-
-
6.7
benzyloxycarbonyl-Pro-Gly-Arg-4-nitroanilide
-
-
0.056
benzyloxycarbonyl-Ser-Arg-SCH2CH(CH3)2
-
-
0.96
benzyloxycarbonyl-Ser-Phe-Arg-4-nitroanilide
-
-
0.054
benzyloxycarbonyl-Thr-Arg-SCH2CH(CH3)2
-
-
0.046
benzyloxycarbonyl-Val-Arg-SCH2CH(CH3)2
-
-
-
0.021 - 0.19
D-Pro-Phe-Arg-4-nitroanilide
0.018
Nalpha-benzoyl-Ile-Glu(-OR)-Gly-Arg-4-nitroanilide
-
-
0.054
Pro-Phe-Arg-4-methylcoumarin 7-amide
-
-
0.18
tert-butyloxycarbonyl-Arg-SCH2C6H5
-
-
-
0.095
tert-butyloxycarbonyl-Arg-SCH2CH(CH3)2
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
15
benzyloxycarbonyl-Ala-Arg-SCH2C6H5
Homo sapiens
-
-
14
benzyloxycarbonyl-Ala-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
34.6
benzyloxycarbonyl-Ala-Phe-Arg-4-nitroanilide
Homo sapiens
-
-
22
benzyloxycarbonyl-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
18 - 23
benzyloxycarbonyl-Asn-Gly-Arg-4-nitroanilide
23
benzyloxycarbonyl-Asn-Phe-Arg-4-nitroanilide
Homo sapiens
-
-
9.2
benzyloxycarbonyl-Glu-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
43
benzyloxycarbonyl-Gly-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
15
benzyloxycarbonyl-Lys-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
25
benzyloxycarbonyl-Lys-Gly-Arg-4-nitroanilide
Homo sapiens
-
-
23
benzyloxycarbonyl-Lys-Phe-Arg-4-nitroanilide
Homo sapiens
-
-
2.5
benzyloxycarbonyl-Met-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
8.3
benzyloxycarbonyl-Phe-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
14
benzyloxycarbonyl-Phe-Gly-Arg-4-nitroanilide
Homo sapiens
-
-
8.3
benzyloxycarbonyl-Pro-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
9.2
benzyloxycarbonyl-Pro-Gly-Arg-4-nitroanilide
Homo sapiens
-
-
13
benzyloxycarbonyl-Ser-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
28
benzyloxycarbonyl-Ser-Phe-Arg-4-nitroanilide
Homo sapiens
-
-
11
benzyloxycarbonyl-Thr-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
17
benzyloxycarbonyl-Val-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
-
14 - 15
D-Pro-Phe-Arg-4-nitroanilide
23
Nalpha-benzoyl-Ile-Glu(-OR)-Gly-Arg-4-nitroanilide
Homo sapiens
-
-
1.9
Pro-Phe-Arg-4-methylcoumarin 7-amide
Homo sapiens
-
-
2.9
tert-butyloxycarbonyl-Arg-SCH2C6H5
Homo sapiens
-
-
-
9.2
tert-butyloxycarbonyl-Arg-SCH2CH(CH3)2
Homo sapiens
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000115 - 0.000287
histidine-rich glycoprotein
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
temperature not specified in the publication
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
highly purified coagulation beta-FXIIa
Manually annotated by BRENDA team
-
cultured in serum-free medium
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
FXII binds tightly to U-937 cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
FXIIa, but not FXII, binds to the extracellular matrix
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10000
-
the human enzyme is a mixture of two forms, one form is composed of two chains, x * 28000 + x * 52000, a second enzyme form, x * 10000 + x * 28000 + x * 40000
30000
-
x * 30000, SDS-PAGE
31000
-
1 * 31000 + 1 * 52000, SDS-PAGE
40000
-
the human enzyme is a mixture of two forms, one form is composed of two chains, x * 28000 + x * 52000, a second enzyme form, x * 10000 + x * 28000 + x * 40000
46000
-
1 * 28000 + 1 * 46000, heavy chain and light chain held together by disulfide bonds
74000
-
sedimentation equilibrium centrifugation
80000
-
proenzyme FXII, SDS-PAGE
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
sulfatides enhance the binding of factor XII to a matrix protein expressed during growth of the endothelial cells. Binding is independent of Zn2+ and specific for alpha-XIIa with a dissociation constant of 12.8 nM
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
side-chain modification
-
the heavy chain contains one Asn-linked and six probable O-linked carbohydrate chains, carbohydrate attachment sites at positions 280, 286, 289, 309, 310, and 318
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, stable for at least several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the cDNA of the zymogen domain of FXII is cloned into the pET-28a(+) vector and the plasmid is transformed into Escherichia coli strain BL21 (DE3) and overexpressed. The multi-disulfide, recombinant zymogen domain His(6)-beta-FXII is expressed as an inclusion body and purified by Ni2+-charged resin
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
FXII gene sequence determination, genotyping
-
genotyping, determination and analysis of mutant K346N gene sequence, transient expression of wild-type and K346N mutant FXII in CHO-K1 cells. Quantitative RT-PCR FXII mRNA expression analysis
-
the cDNA of the zymogen domain of FXII is cloned into the pET-28a(+) vector and the plasmid is transformed into Escherichia coli strain BL21 (DE3) and overexpressed
-
the FXII promoter contains the -299/+1 region, that is sufficient for TGF-beta1 to induce FXII expression
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
monocyte-derived microparticles increase FXIIa activity, but to a lesser extent than platelet- and erythrocyte-derived microparticles
-
transforming growth factor-beta1, TGF-beta1, a multifunctional cytokine, induces FXII expression, which is specifically repressed by the JNK inhibitor, and by JNK and Smad3 antisense oligonucleotides, but not by MEK, p38, or phosphoinositide 3-kinase blockers, overview. Treatment of human lung fibroblasts with TGF-beta1 results in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. The FXII promoter contains the -299/+1 region, that is sufficient for TGF-beta1 to induce FXII expression, but the activation of FXII expression also requires Smad binding to TGF-beta1 at the a potential Smad binding element at position -272/-269 (SBE-(-272/-269)) of the TGF-beta1 promoter. JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A324P/G531E
-
naturally occuring mutation, reduced activity of prekallikrein cleavage
C135X
-
naturally occuring mutation, Korean patient 2
G582S
-
mutation of c11744G>A plus insertion mutation c1093_1094insC, pK365QfsX69, naturally occuring mutation, Korean patient 3
K346N
-
the mutation, a G to C point mutation at nucleotide 9845, causes a replacement in the catalytic domain, and congenital FXII deficiency as a rare coagulation disease and an autosomal recessive trait, designated as factor XII Ofunato. The mutant shows a lower level of accumulation in the cells and reduced secretion in culture medium.compared to the wild-type. The mutant shows unaltered FXII mRNA levels but increased degenration of the mutant mRNA in the pre-Golgi compartment of transfected CHO-K1 cells involving the proteasome, overview
P547L
-
the mutation is associated with factor XII deficiency
Q501T
-
the mutation is associated with factor XII deficiency
S528T/G582S
-
naturally occuring mutation, Korean patient 1
T309K
-
naturally occuring mutation of factor XII, isolated from hereditary angioedema patients. The mutation does not affect FXII surface activation or kallikrein-like activity, and does not lead to a gain-of-function of FXIIa, overview
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
synthesis
-
the enzyme is used for preparation of factor Xia and plasma kallikrein