Information on EC 3.4.21.B43 - kallikrein 12

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The expected taxonomic range for this enzyme is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.4.21.B43
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
kallikrein 12
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
proteolytic cleavage of polypeptides
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
342900-25-8
-
9001-01-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
PDGF-B is probably one of the molecules linking the interaction between enzyme-induced endothelial cells and fibroblasts. Expression of both KLK12 and PDGFB genes is regulated by hypoxia in the lung tumor microenvironment
physiological function
additional information
-
KLK12 is a trypsin-like kallikrein-related peptidase that is abundant in a variety of human tissues
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Abz-ISLMKYRPPGF-(3-NO2)-Tyr + H2O
?
show the reaction diagram
-
very low activity
-
-
?
Abz-SPFRSSR-(3-NO2)-Tyr + H2O
?
show the reaction diagram
-
low activity
-
-
?
alpha2-antiplasmin + H2O
?
show the reaction diagram
-
-
-
-
?
Antithrombin III + H2O
?
show the reaction diagram
-
-
-
-
?
Boc-VPR-7-amido-4-methylcoumarin + H2O
Boc-VPR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
C1 inhibitor + H2O
?
show the reaction diagram
-
-
-
-
?
CCN1 protein + H2O
?
show the reaction diagram
-
i.e. (cyr61,ctgf, nov), the main cleavage site is localized in the hinge region between the first and second half of the recombinant protein at Lys88-Gly89, Lys208-Arg209, Arg218-Ile219, Lys291-Lys292, and Lys345-Asn346
-
-
?
CCN2 protein + H2O
?
show the reaction diagram
-
-
-
-
?
CCN3 protein + H2O
?
show the reaction diagram
-
-
-
-
?
CCN4 protein + H2O
?
show the reaction diagram
-
-
-
-
?
CCN5 protein + H2O
?
show the reaction diagram
-
cleavage site is at Arg215-Val216
-
-
?
CCN6 protein + H2O
?
show the reaction diagram
-
-
-
-
?
D-Val-Leu-Lys-thiobenzyl ester + H2O
D-Val-Leu-Lys + thiobenzyl alcohol
show the reaction diagram
-
100% activity
-
-
?
high molecular weight kininogen + H2O
?
show the reaction diagram
-
proteolysis pattern, overview. Release of bradykinin, a fragment containing the C-terminal end of kinins. The kininogenase activity of the enzyme is poor due to the resistance of hydrolysis of the K-R bond on the N-terminal side of the bradykinin sequence in the kininogen
-
-
?
influenza hemagglutinin precursor + H2O
mature influenza hemagglutinin + ?
show the reaction diagram
platelet-derived growth factor B precursor + H2O
mature platelet-derived growth factor B + ?
show the reaction diagram
-
membrane bound zymogen
soluble mature paracrine factor, soluble mature protein
-
?
polypeptide + H2O
peptides
show the reaction diagram
protein C inhibitor + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-DPR-7-amido-4-methylcoumarin + H2O
tert-butyloxycarbonyl-DPR + 7-amino-4-methylcoumarin
show the reaction diagram
-
55% activity compared to D-Val-Leu-Lys-thiobenzyl ester
-
-
?
tert-butyloxycarbonyl-FSR-7-amido-4-methylcoumarin + H2O
tert-butyloxycarbonyl-FSR + 7-amino-4-methylcoumarin
show the reaction diagram
-
13% activity compared to D-Val-Leu-Lys-thiobenzyl ester
-
-
?
tert-butyloxycarbonyl-QAR-7-amido-4-methylcoumarin + H2O
tert-butyloxycarbonyl-QAR + 7-amino-4-methylcoumarin
show the reaction diagram
-
98% activity compared to D-Val-Leu-Lys-thiobenzyl ester
-
-
?
tert-butyloxycarbonyl-VPR-7-amido-4-methylcoumarin + H2O
tert-butyloxycarbonyl-VPR + 7-amino-4-methylcoumarin
show the reaction diagram
-
85% activity compared to D-Val-Leu-Lys-thiobenzyl ester
-
-
?
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
CCN1 protein + H2O
?
show the reaction diagram
-
i.e. (cyr61,ctgf, nov), the main cleavage site is localized in the hinge region between the first and second half of the recombinant protein at Lys88-Gly89, Lys208-Arg209, Arg218-Ile219, Lys291-Lys292, and Lys345-Asn346
-
-
?
CCN2 protein + H2O
?
show the reaction diagram
-
-
-
-
?
CCN3 protein + H2O
?
show the reaction diagram
-
-
-
-
?
CCN4 protein + H2O
?
show the reaction diagram
-
-
-
-
?
CCN5 protein + H2O
?
show the reaction diagram
-
cleavage site is at Arg215-Val216
-
-
?
CCN6 protein + H2O
?
show the reaction diagram
-
-
-
-
?
influenza hemagglutinin precursor + H2O
mature influenza hemagglutinin + ?
show the reaction diagram
-
the enzyme shows a preference for the H1 and H2 subtypes, the amino acids neighboring the arginine cleavage site affect cleavage efficiency
-
-
?
platelet-derived growth factor B precursor + H2O
mature platelet-derived growth factor B + ?
show the reaction diagram
-
membrane bound zymogen
soluble mature paracrine factor
-
?
polypeptide + H2O
peptides
show the reaction diagram
Q9UKR0
involved in posttranslational processing of polypeptide precursors
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3,4-dichloroisocoumarin
-
strong inhibitor at 0.25 mM
Alpha1-antitrypsin
-
less than 50% inhibition at 5fold molecular inhibitor excess
-
alpha2-antiplasmin
-
-
-
antithrombin-III
-
less than 50% inhibition at 5fold molecular inhibitor excess
-
Aprotinin
-
weak inhibition at 0.02 mM
benzamidine
-
strong inhibitor at 5 mM
C1 inhibitor
-
-
-
NaCl
-
activity is reduced by approximately 30% in the presence of 0.8 M NaCl
Protein C inhibitor
-
-
-
Zn2+
-
10 mM Zn2+ is sufficient to inhibit 50% of the KLK12 enzyme activity, more than 95% suppression can be achieved by 0.2 mM Zn2+
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
the activity of KLK12 can be tightly regulated by autodegradation, by interaction with zinc ions, and by covalent complex formation with alpha2-antiplasmin
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0294
D-Val-Leu-Lys-thiobenzyl ester
-
in 0.1 M Tris, 10 mM CaCl2, 0.15 M NaCl, pH 8.0, at 37C
0.35
tert-butyloxycarbonyl-DPR-7-amido-4-methylcoumarin
-
in 0.1 M Tris, 10 mM CaCl2, 0.15 M NaCl, pH 8.0, at 37C
0.565
tert-butyloxycarbonyl-FSR-7-amido-4-methylcoumarin
-
in 0.1 M Tris, 10 mM CaCl2, 0.15 M NaCl, pH 8.0, at 37C
0.0686
tert-butyloxycarbonyl-QAR-7-amido-4-methylcoumarin
-
in 0.1 M Tris, 10 mM CaCl2, 0.15 M NaCl, pH 8.0, at 37C
0.2
tert-butyloxycarbonyl-VPR-7-amido-4-methylcoumarin
-
in 0.1 M Tris, 10 mM CaCl2, 0.15 M NaCl, pH 8.0, at 37C
additional information
additional information
-
enzyme reaction kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
12.42
D-Val-Leu-Lys-thiobenzyl ester
Homo sapiens
-
in 0.1 M Tris, 10 mM CaCl2, 0.15 M NaCl, pH 8.0, at 37C
0.017 - 32.65
tert-butyloxycarbonyl-DPR-7-amido-4-methylcoumarin
0.052 - 10.06
tert-butyloxycarbonyl-FSR-7-amido-4-methylcoumarin
0.97 - 17.26
tert-butyloxycarbonyl-QAR-7-amido-4-methylcoumarin
8.1 - 25.81
tert-butyloxycarbonyl-VPR-7-amido-4-methylcoumarin
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
3,4-dichloroisocoumarin
Homo sapiens
-
-
0.28
benzamidine
Homo sapiens
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
-
-
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
low content
Manually annotated by BRENDA team
-
gene expression of the enzyme is down-regulated in breast cancer; low content
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
very low content
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the enzyme is secreted
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28000
-
SDS-PAGE, tagged enzyme
38000
-
SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 24500, calculated from amino acid sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
activation of the proform of the enzyme, pro-KLK12
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7
-
when the pH is decreased to less than 5.0, KLK12 enzyme activity becomes undetectable, KLK12 activity is very sensitive to pH changes in the range 6.5-7.0 (within this range, a decrease of 0.5 pH units results in a more than 60% reduction in activity)
678534
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Brij-35
-
adding 10-20% glycerol and 0.05% Brij-35 to the KLK12 autoactivation mixture can slow down activation
Glycerol
-
adding 10-20% glycerol and 0.05% Brij-35 to the KLK12 autoactivation mixture can slow down activation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
37C, 12.5 mM MES, 75 mM NaCl, after 16 h, 24 h, 48 h, and 72 h only 50%, 35%, 20%, and 10% of the initial activity is detected
-
37C, in the presence of 10-20% glycerol and 0.05% Brij-35, 72 h, 10% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity chromatography and gel filtration
-
Ni-NTA agarose column chromatography and reversed-phase high performance liquid chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli strain BL21(DE3)
-
expressed in NS0 myeloma cell line
-
gene KLK12, formerly KLK5, DNA sequence determination and analysis, chromosome mapping to 19q13.3-13.4, splice variants identification, genomic organization
-
the gene is located on chromosome 19q13.4, splice variants KLK12sv3 and KLK12sv1/KLK12sv2 in breast cancer cells by quantitative real-time PCR as well as semi-quantitative PCR expression analysis
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Expression of both KLK12 and PDGFB genes is regulated by hypoxia in the lung tumor microenvironment
-
KLK12 expression is increased in lung tumor
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
enzyme splice variant KLK12sv3 can be regarded as a marker of good prognosis in breast cancer