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Information on EC 3.4.21.38 - coagulation factor XIIa and Organism(s) Homo sapiens and UniProt Accession P00748

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     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.38 coagulation factor XIIa
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This record set is specific for:
Homo sapiens
UNIPROT: P00748 not found.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
selective cleavage of Arg-/-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa
Synonyms
factor xii, hageman factor, fxiia, factor xiia, coagulation factor xii, activated factor xii, prekallikrein activator, beta-factor xiia, blood coagulation factor xii, coagulation factor xiia, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
beta-factor XIIa
-
beta-FXIIa
-
coagulation factor XII
-
coagulation factor XIIa
-
factor XII
-
Hageman factor
-
activated coagulation factor XII
-
-
activated factor XII
-
-
alpha-FXIIa
-
-
alphaFXIIa
-
-
beta-FXIIa
blood coagulation factor XII
-
-
blood-coagulation factor XII, activated beta
-
-
-
-
blood-coagulation factor XIIabeta
-
-
-
-
blood-coagulation factor XIIf
-
-
-
-
coagulation beta-factor XIIa
-
-
coagulation factor XII
-
-
factor XII Osaka
-
abnormal factor XII with partially defective prekallikrein cleavage activity
FXIIa
HAF
-
-
-
-
Hageman factor
Hageman factor beta-fragment
-
-
-
-
Hageman factor fragment HFf
-
-
-
-
Hagemann factor
-
-
-
-
kallikreinogen, activator
-
-
-
-
prealbumin activator
-
-
-
-
prekallikrein activator
-
-
-
-
single-chain FXII
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
75216-42-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
factor XI + H2O
factor XIa + ?
show the reaction diagram
prekallikrein + H2O
kallikrein + kallikrein prepeptide
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
factor VIIa
show the reaction diagram
-
-
-
?
factor XI + H2O
factor XIa + ?
show the reaction diagram
-
-
-
-
?
factor XII + H2O
factor XIIa + ?
show the reaction diagram
-
the enzyme undergoes autoactivation to alpha-fXIIa in the presence of polyphosphate
-
-
?
Nalpha-benzoyl-Ile-Glu(-OR)-Gly-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-Ile-Glu(-OR)-Gly-Arg + 4-nitroaniline
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
-
-
-
-
?
plasma prekallikrein + H2O
plasma kallikrein + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
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 + ?
show the reaction diagram
-
-
-
-
?
prekallikrein + H2O
kallikrein + kallikrein prepeptide
show the reaction diagram
Pro-Phe-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
S-2251 + H2O
?
show the reaction diagram
-
-
-
-
?
S-2302 + 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
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
factor XI + H2O
factor XIa + ?
show the reaction diagram
prekallikrein + H2O
kallikrein + kallikrein prepeptide
show the reaction diagram
-
-
-
?
factor XI + H2O
factor XIa + ?
show the reaction diagram
-
-
-
-
?
plasma prekallikrein + H2O
plasma kallikrein + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
prekallikrein + H2O
kallikrein + ?
show the reaction diagram
-
-
-
-
?
prekallikrein + H2O
kallikrein + kallikrein prepeptide
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-((1-aminoisoquinolin-6-yl)phenyl)boronic acid
-
antithrombin
minor inhibitory activity
-
benzamidine
-
corn trypsin inhibitor
-
-
plasminogen activator inhibitor 1
minor inhibitory activity
serpin C1 esterase inhibitor
-
-
Ala-Phe-Arg-chloromethylketone
-
-
alpha2-Macroglobulin
-
-
-
antithrombin III
-
-
-
C1 esterase inhibitor
-
-
-
C1 inhibitor
-
-
-
C1INH
-
-
-
corn trypsin inhibitor
-
D-Pro-Phe-Arg-chloromethyl ketone
-
-
dansyl-Glu-Gly-Arg-chloromethylketone
-
-
histidine-rich glycoprotein
-
inhibitor of autoactivation, inhibitor of activation of factor XI
-
Ir-CPI
-
the recombinant Ixodes ricinus contact phase inhibitor, a Kunitz type protein expressed by the salivary glands of the tick Ixodes ricinus, specifically interacts with activated human contact phase factors FXIIa, FXIa, and kallikrein. Ir-CPI inhibits the activation of contact system factors, and it prolongs the activated partial thromboplastin time in vitro. Effects of Ir-CPI in vivo are determined using both venous and arterial thrombosis models, overview
-
Phe-Phe-Arg-chloromethylketone
-
-
Phe-Pro-Arg-chloromethylketone
-
-
Pro-Phe-Arg chloromethylketone
Pumpkin seed inhibitor
-
the inhibitor is isolated from Cucurbita maxima, minimum MW is 3268 Da
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
High molecular weight kininogen
-
-
long-chain polyphosphate
-
-
plasma prekallikrein
-
-
alpha-kallikrein
-
-
-
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
Kallikrein
-
mediates activation of the zymogen FXII
-
kaolin
-
-
-
plasma kallikrein
-
-
-
Polyphosphate
-
-
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
-
-
0.0008 - 0.0017
prekallikrein
-
0.054
Pro-Phe-Arg-4-methylcoumarin 7-amide
-
-
0.1 - 2.7
S-2302
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
-
-
14
benzyloxycarbonyl-Ala-Arg-SCH2CH(CH3)2
-
-
34.6
benzyloxycarbonyl-Ala-Phe-Arg-4-nitroanilide
-
-
22
benzyloxycarbonyl-Arg-SCH2CH(CH3)2
-
-
18 - 23
benzyloxycarbonyl-Asn-Gly-Arg-4-nitroanilide
23
benzyloxycarbonyl-Asn-Phe-Arg-4-nitroanilide
-
-
9.2
benzyloxycarbonyl-Glu-Arg-SCH2CH(CH3)2
-
-
43
benzyloxycarbonyl-Gly-Arg-SCH2CH(CH3)2
-
-
15
benzyloxycarbonyl-Lys-Arg-SCH2CH(CH3)2
-
-
25
benzyloxycarbonyl-Lys-Gly-Arg-4-nitroanilide
-
-
23
benzyloxycarbonyl-Lys-Phe-Arg-4-nitroanilide
-
-
2.5
benzyloxycarbonyl-Met-Arg-SCH2CH(CH3)2
-
-
8.3
benzyloxycarbonyl-Phe-Arg-SCH2CH(CH3)2
-
-
14
benzyloxycarbonyl-Phe-Gly-Arg-4-nitroanilide
-
-
8.3
benzyloxycarbonyl-Pro-Arg-SCH2CH(CH3)2
-
-
9.2
benzyloxycarbonyl-Pro-Gly-Arg-4-nitroanilide
-
-
13
benzyloxycarbonyl-Ser-Arg-SCH2CH(CH3)2
-
-
28
benzyloxycarbonyl-Ser-Phe-Arg-4-nitroanilide
-
-
11
benzyloxycarbonyl-Thr-Arg-SCH2CH(CH3)2
-
-
17
benzyloxycarbonyl-Val-Arg-SCH2CH(CH3)2
-
-
14 - 15
D-Pro-Phe-Arg-4-nitroanilide
23
Nalpha-benzoyl-Ile-Glu(-OR)-Gly-Arg-4-nitroanilide
-
-
0.000062 - 0.73
prekallikrein
-
1.9
Pro-Phe-Arg-4-methylcoumarin 7-amide
-
-
0.108 - 11.7
S-2302
2.9
tert-butyloxycarbonyl-Arg-SCH2C6H5
-
-
9.2
tert-butyloxycarbonyl-Arg-SCH2CH(CH3)2
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.077 - 4333
prekallikrein
-
0.4 - 116.7
S-2302
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
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
highly purified coagulation beta-FXIIa
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
FXII deficiency in Korean patients leads to prolonged activated partial thromboplastin time
physiological function
malfunction
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
FA12_HUMAN
615
0
67792
Swiss-Prot
Secretory Pathway (Reliability: 1)
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
28000
-
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
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
52000
-
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
80000
-
proenzyme FXII, SDS-PAGE
additional information
SUBUNIT
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with benzamidine or 3-((1-aminoisoquinolin-6-yl)phenyl)boronic acid, vapor diffusion method, using 0.2 M ammonium iodide, 2.2 M ammonium sulfate
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C135X
naturally occuring mutation, Korean patient 2
G582S
mutation of c11744G>A plus insertion mutation c1093_1094insC, pK365QfsX69, naturally occuring mutation, Korean patient 3
S528T/G582S
naturally occuring mutation, Korean patient 1
A324P/G531E
-
naturally occuring mutation, reduced activity of prekallikrein cleavage
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
R334A/R343A/R353A
-
the mutant lacks the Arg334, Arg343, and Arg353 cleavage sites required for conversion to the enzyme form betaFXIIa and shows proteolytic activity that is about 3000fold weaker than that of the wild type enzyme
R334A/R344A/R353A
-
in the presence of polyphosphate, the mutant converts factor XII to its active form alpha-fXIIa, and also converts factor XI to its active form fXIa. The mutant does not undergo autocatalysis to alpha-fXIIa in the presence of polyphosphate, and is resistant to cleavage by alpha-kallikrein and factor XIIa
R353A
-
the mutant lacks the Arg353 cleavage site required for conversion to the activated enzyme form alphaFXIIa and shows proteolytic activity that is several orders of magnitude weaker than that of the wild type enzyme
S544A
-
active site mutant
S554A
-
inactive
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
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
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
plasma variations of different types of XIIa following thrombolytic treatment analyzed
drug development
-
a contact phase inhibitor of FXIIa is an effective and safe antithrombotic agent in vivo
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
McMullen, B.A.; Fujikawa, K.
Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor)
J. Biol. Chem.
260
5328-5341
1985
Homo sapiens
Manually annotated by BRENDA team
Silverberg, M.; Kaplan, A.P.
Enzymatic activities of activated and zymogen forms of human Hageman factor (factor XII)
Blood
60
64-70
1982
Homo sapiens
Manually annotated by BRENDA team
Hojima, Y.; Pierce, J.V.; Pisano, J.J.
Pumpkin seed inhibitor of human factor XIIa (activated Hageman factor) and bovine trypsin
Biochemistry
21
3741-3746
1982
Homo sapiens
Manually annotated by BRENDA team
Semba, U.; Yamamoto, T.; Kunisada, T.; Shibuya, Y.; Tanase, S.; Kambara, T.; Okabe, H.
Primary structure of guinea-pig Hageman factor: sequence around the cleavage site differs from the human molecule
Biochim. Biophys. Acta
1159
113-121
1992
Cavia porcellus, Homo sapiens
Manually annotated by BRENDA team
Ratnoff, O.D.; Saito, H.
Amidolytic properties of single-chain activated Hageman factor
Proc. Natl. Acad. Sci. USA
76
1461-1463
1979
Homo sapiens
Manually annotated by BRENDA team
Que, B.G.; Davie, E.W.
Characterization of a cDNA coding for human factor XII (Hageman Factor)
Biochemistry
25
1525-1528
1986
Homo sapiens
Manually annotated by BRENDA team
Cho, K.; Tanaka, T.; Cook, R.R.; Kisiel, W.; Fujikawa, K.; Kurachi, K.
Active-site mapping of bovine and human blood coagulation serine proteases using synthetic peptide 4-nitroanilide and thio ester substrates
Biochemistry
23
644-650
1984
Homo sapiens
Manually annotated by BRENDA team
Loiseau, C.; Randriamahazaka, H.N.; Nigretto, J.M.
Explicit constants for the dextran-sulfate-mediated activation and autoactivation of purified human factor XII (Hageman factor)
Eur. J. Biochem.
239
692-701
1996
Homo sapiens
Manually annotated by BRENDA team
Nuijens, J.H.; Huijbregts, C.C.M.; Eerenberg-Belmer, A.J.M.; Meijers, J.C.M.; Bouma, B.N.; Hack, C.E.
Activation of the contact system of coagulation by a monoclonal antibody directed against a neodeterminant in the heavy chain region of human coagulation factor XII (Hageman factor)
J. Biol. Chem.
264
12941-12949
1989
Homo sapiens
Manually annotated by BRENDA team
Real, K.J.; Masterson, B.F.
Availability in pooled normal blood plasma of activated Hageman factor and kallikrein for contact induced coagulation
Biochem. Soc. Trans.
26
S274
1998
Homo sapiens
Manually annotated by BRENDA team
Samuel, M.; Samuel, E.; Villanueva, G.B.
The low pH stability of human coagulation factor XII (Hageman factor) is due to reversible conformational transitions
Thromb. Res.
75
259-268
1994
Homo sapiens
Manually annotated by BRENDA team
Fujikawa, K.; Davie, E.W.
Human factor XII (Hageman factor)
Methods Enzymol.
80
198-211
1981
Homo sapiens
Manually annotated by BRENDA team
Silverberg, M.; Kaplan, A.P.
Human Hageman factor and its fragments
Methods Enzymol.
163
68-80
1988
Homo sapiens
Manually annotated by BRENDA team
Yamamoto, T.; Shibuya, Y.; Nishino, N.; Okabe, H.; Kambara, T.
Activation of human Hageman factor by Pseudomonas aeruginosa elastase in the presence or absence of negatively charged substance in vitro
Biochim. Biophys. Acta
1038
231-239
1990
Homo sapiens
Manually annotated by BRENDA team
Shan, J.; Baguinon, M.; Zheng, L.; Krishnamoorthi, R.
Expression, refolding, and activation of the catalytic domain of human blood coagulation factor XII
Protein Expr. Purif.
27
143-149
2003
Homo sapiens
Manually annotated by BRENDA team
Carmona, F.; Lazaro, I.; Reverter, J.C.; Tassies, D.; Font, J.; Cervera, R.; Balasch, J.
Impaired factor XIIa-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications
Am. J. Obstet. Gynecol.
194
457-465
2006
Homo sapiens
Manually annotated by BRENDA team
Lowe, G.D.; Rumley, A.; McMahon, A.D.; Ford, I.; OReilly, D.S.; Packard, C.J.; Packard, C.J.
Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease
Arterioscler. Thromb. Vasc. Biol.
24
1529-1534
2004
Homo sapiens
Manually annotated by BRENDA team
Johne, J.; Blume, C.; Benz, P.M.; Pozgajova, M.; Ullrich, M.; Schuh, K.; Nieswandt, B.; Walter, U.; Renne, T.
Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma
Biol. Chem.
387
173-178
2006
Homo sapiens
Manually annotated by BRENDA team
Latacha, M.P.; Schaiff, W.T.; Eisenberg, P.R.; Abendschein, D.R.
Factor XII-dependent increases in thrombin activity induce carboxypeptidase-mediated attenuation of pharmacological fibrinolysis
J. Thromb. Haemost.
2
128-134
2004
Homo sapiens
Manually annotated by BRENDA team
Schousboe, I.
Endothelial cells express a matrix protein which binds activated factor XII in a zinc-independent manner
Thromb. Haemost.
95
312-319
2006
Homo sapiens
Manually annotated by BRENDA team
Gallimore, M.J.; Harris, S.L.; Jones, D.W.; Winter, M.
Plasma levels of factor XII, prekallikrein and high molecular weight kininogen in normal blood donors and patients having suffered venous thrombosis
Thromb. Res.
114
91-96
2004
Homo sapiens
Manually annotated by BRENDA team
Poenitz, V.; Pritchard, D.; Grundt, H.; Nilsen, D.W.
Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase
J. Thromb. Thrombolysis
22
199-203
2006
Homo sapiens (P00748), Homo sapiens
Manually annotated by BRENDA team
Kravtsov, D.V.; Matafonov, A.; Tucker, E.I.; Sun, M.F.; Walsh, P.N.; Gruber, A.; Gailani, D.
Factor XI contributes to thrombin generation in the absence of factor XII
Blood
114
452-458
2009
Homo sapiens
Manually annotated by BRENDA team
Matsubayashi, H.; Sugi, T.; Suzuki, T.; Uchida, N.; Atsumi, H.; Izumi, S.; Mikami, M.
Decreased factor XII activity is associated with recurrent IVF-ET failure
Am. J. Reprod. Immunol.
59
316-322
2008
Homo sapiens
Manually annotated by BRENDA team
Barbasz, A.; Kozik, A.
The assembly and activation of kinin-forming systems on the surface of human U-937 macrophage-like cells
Biol. Chem.
390
269-275
2009
Homo sapiens
Manually annotated by BRENDA team
Lombardi, A.M.; Bortoletto, E.; Scarparo, P.; Scapin, M.; Santarossa, L.; Girolami, A.
Genetic study in patients with factor XII deficiency: a report of three new mutations exon 13 (Q501STOP), exon 14 (P547L) and -13C>T promoter region in three compound heterozygotes
Blood Coagul. Fibrinolysis
19
639-643
2008
Homo sapiens
Manually annotated by BRENDA team
Okorie, U.M.; Denney, W.S.; Chatterjee, M.S.; Neeves, K.B.; Diamond, S.L.
Determination of surface tissue factor thresholds that trigger coagulation at venous and arterial shear rates: amplification of 100 fM circulating tissue factor requires flow
Blood
111
3507-3513
2008
Homo sapiens
Manually annotated by BRENDA team
Stoll, G.; Kleinschnitz, C.; Nieswandt, B.
Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment
Blood
112
3555-3562
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Schousboe, I.; Nystrom, B.T.; Hansen, G.H.
Differential binding of factor XII and activated factor XII to soluble and immobilized fibronectin--localization of the Hep-1/Fib-1 binding site for activated factor XII
FEBS J.
275
5161-5172
2008
Homo sapiens
Manually annotated by BRENDA team
Schmaier, A.H.
The elusive physiologic role of Factor XII
J. Clin. Invest.
118
3006-3009
2008
Homo sapiens
Manually annotated by BRENDA team
Davis, A.E.; Mejia, P.; Lu, F.
Biological activities of C1 inhibitor
Mol. Immunol.
45
4057-4063
2008
Homo sapiens
Manually annotated by BRENDA team
Reuner, K.H.; Jenetzky, E.; Aleu, A.; Litfin, F.; Mellado, P.; Kloss, M.; Juettler, E.; Grau, A.J.; Rickmann, H.; Patscheke, H.; Lichy, C.
Factor XII C46T gene polymorphism and the risk of cerebral venous thrombosis
Neurology
70
129-132
2008
Homo sapiens
Manually annotated by BRENDA team
Melo, F.R.; Mourao, P.A.
An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor XII and inhibition of the coagulation proteases
Thromb. Haemost.
99
531-538
2008
Homo sapiens
Manually annotated by BRENDA team
Fink, H.; Faxaelv, L.; Molnar, G.F.; Drotz, K.; Risberg, B.; Lindahl, T.L.; Sellborn, A.
Real-time measurements of coagulation on bacterial cellulose and conventional vascular graft materials
Acta Biomater.
6
1125-1130
2010
Homo sapiens
Manually annotated by BRENDA team
Vogler, E.A.; Siedlecki, C.A.
Contact activation of blood-plasma coagulation
Biomaterials
30
1857-1869
2009
Bos taurus, Gallus gallus, Equus caballus, Homo sapiens
Manually annotated by BRENDA team
Chatterjee, K.; Thornton, J.L.; Bauer, J.W.; Vogler, E.A.; Siedlecki, C.A.
Moderation of prekallkrein-factor XII interactions in surface activation of coagulation by protein-adsorption competition
Biomaterials
30
4915-4920
2009
Homo sapiens
Manually annotated by BRENDA team
Bork, K.; Kleist, R.; Hardt, J.; Witzke, G.
Kallikrein-kinin system and fibrinolysis in hereditary angioedema due to factor XII gene mutation Thr309Lys
Blood Coagul. Fibrinolysis
20
325-332
2009
Homo sapiens
Manually annotated by BRENDA team
Kwon, M.J.; Kim, H.J.; Lee, K.O.; Jung, C.W.; Kim, S.H.
Molecular genetic analysis of Korean patients with coagulation factor XII deficiency
Blood Coagul. Fibrinolysis
21
308-312
2010
Homo sapiens (P00748), Homo sapiens
Manually annotated by BRENDA team
Papageorgiou, P.C.; Simos, D.; Boomsma, F.; Rojkjaer, R.; Osmond, D.H.
Angiotensin converting enzyme-regulated, noncholinergic sympathoadrenal catecholamine release mediates the cardiovascular actions of human new pressor protein related to coagulation beta-factor XIIa
Can. J. Cardiol.
25
e100-e108
2009
Homo sapiens
Manually annotated by BRENDA team
Wang, R.; Zhang, T.; Ma, Z.; Wang, Y.; Cheng, Z.; Xu, H.; Li, W.; Wang, X.
The interaction of coagulation factor XII and monocyte/macrophages mediating peritoneal metastasis of epithelial ovarian cancer
Gynecol. Oncol.
117
460-466
2010
Homo sapiens
Manually annotated by BRENDA team
Jablonska, E.; Markart, P.; Zakrzewicz, D.; Preissner, K.T.; Wygrecka, M.
Transforming growth factor-beta1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts
J. Biol. Chem.
285
11638-11651
2010
Homo sapiens
Manually annotated by BRENDA team
Chatterjee, K.; Guo, Z.; Vogler, E.; Siedlecki, C.
Contributions of contact activation pathways of coagulation factor XII in plasma
J. Biomed. Mater. Res. A
90
27-34
2009
Homo sapiens
Manually annotated by BRENDA team
Decrem, Y.; Rath, G.; Blasioli, V.; Cauchie, P.; Robert, S.; Beaufays, J.; Frere, J.M.; Feron, O.; Dogne, J.M.; Dessy, C.; Vanhamme, L.; Godfroid, E.
Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis
J. Exp. Med.
206
2381-2395
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Suzuki, K.; Murai, K.; Suwabe, A.; Ishida, Y.
Factor XII Ofunato: Lys346Asn mutation associated with blood coagulation factor XII deficiency causes impaired secretion through a proteasome-mediated degradation
Thromb. Res.
125
438-443
2010
Homo sapiens
Manually annotated by BRENDA team
Bck, J.; Sanchez, J.; Elgue, G.; Ekdahl, K.; Nilsson, B.
Activated human platelets induce factor XIIa-mediated contact activation
Biochem. Biophys. Res. Commun.
391
11-17
2010
Homo sapiens
Manually annotated by BRENDA team
MacQuarrie, J.L.; Stafford, A.R.; Yau, J.W.; Leslie, B.A.; Vu, T.T.; Fredenburgh, J.C.; Weitz, J.I.
Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation
Blood
117
4134-4141
2011
Homo sapiens
Manually annotated by BRENDA team
Iijima, K.; Arakawa, Y.; Sugahara, Y.; Matsushita, M.; Moriguchi, Y.; Shimohiro, H.; Nakagawa, M.
Factor XII Osaka: Abnormal factor XII with partially defective prekallikrein cleavage activity
Thromb. Haemost.
105
473-478
2011
Homo sapiens
Manually annotated by BRENDA team
Kuijpers, M.J.; van der Meijden, P.E.; Feijge, M.A.; Mattheij, N.J.; May, F.; Govers-Riemslag, J.; Meijers, J.C.; Heemskerk, J.W.; Renne, T.; Cosemans, J.M.
Factor XII regulates the pathological process of thrombus formation on ruptured plaques
Arterioscler. Thromb. Vasc. Biol.
34
1674-1680
2014
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Van Der Meijden, P.E.; Van Schilfgaarde, M.; Van Oerle, R.; Renne, T.; ten Cate, H.; Spronk, H.M.
Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa
J. Thromb. Haemost.
10
1355-1362
2012
Homo sapiens
Manually annotated by BRENDA team
Puy, C.; Tucker, E.I.; Wong, Z.C.; Gailani, D.; Smith, S.A.; Choi, S.H.; Morrissey, J.H.; Gruber, A.; McCarty, O.J.
Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates
J. Thromb. Haemost.
11
1341-1352
2013
Homo sapiens (P00748)
Manually annotated by BRENDA team
Sylman, J.; Daalkhaijav, U.; Zhang, Y.; Gray, E.; Farhang, P.; Chu, T.; Zilberman-Rudenko, J.; Puy, C.; Tucker, E.; Smith, S.; Morrissey, J.; Walker, T.; Nan, X.; Gruber, A.; McCarty, O.
Differential roles for the coagulation factors XI and XII in regulating the physical biology of fibrin
Ann. Biomed. Eng.
45
1328-1340
2017
Homo sapiens
Manually annotated by BRENDA team
Ivanov, I.; Matafonov, A.; Sun, M.F.; Cheng, Q.; Dickeson, S.K.; Verhamme, I.M.; Emsley, J.; Gailani, D.
Proteolytic properties of single-chain factor XII a mechanism for triggering contact activation
Blood
129
1527-1537
2017
Homo sapiens
Manually annotated by BRENDA team
Dementiev, A.; Silva, A.; Yee, C.; Li, Z.; Flavin, M.T.; Sham, H.; Partridge, J.R.
Structures of human plasma beta-factor XIIa cocrystallized with potent inhibitors
Blood Adv.
2
549-558
2018
Homo sapiens (P00748), Homo sapiens
Manually annotated by BRENDA team
Ivanov, I.; Matafonov, A.; Gailani, D.
Single-chain factor XII a new form of activated factor XII
Curr. Opin. Hematol.
24
411-418
2017
Homo sapiens
Manually annotated by BRENDA team
Wujak, L.; Didiasova, M.; Zakrzewicz, D.; Frey, H.; Schaefer, L.; Wygrecka, M.
Heparan sulfate proteoglycans mediate factor XIIa binding to the cell surface
J. Biol. Chem.
290
7027-7039
2015
Homo sapiens
Manually annotated by BRENDA team
Hess, R.; Wujak, L.; Hesse, C.; Sewald, K.; Jonigk, D.; Warnecke, G.; Fieguth, H.G.; de Maat, S.; Maas, C.; Bonella, F.; Preissner, K.T.; Weiss, B.; Schaefer, L.; Kuebler, W.M.; Markart, P.; Wygrecka, M.
Coagulation factor XII regulates inflammatory responses in human lungs
Thromb. Haemost.
117
1896-1907
2017
Homo sapiens
Manually annotated by BRENDA team
Konings, J.; Hoving, L.R.; Ariens, R.S.; Hethershaw, E.L.; Ninivaggi, M.; Hardy, L.J.; de Laat, B.; Ten Cate, H.; Philippou, H.; Govers-Riemslag, J.W.
The role of activated coagulation factor XII in overall clot stability and fibrinolysis
Thromb. Res.
136
474-480
2015
Homo sapiens
Manually annotated by BRENDA team