3.4.21.109: matriptase
This is an abbreviated version!
For detailed information about matriptase, go to the full flat file.
Word Map on EC 3.4.21.109
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3.4.21.109
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hepatocyte
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hepcidin
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hai-1
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anemia
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metastasis
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prostate
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hepsin
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zymogen
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transferrin
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prostasin
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overload
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trypsin-like
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irida
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plasminogen
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hemojuvelin
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iron-refractory
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kunitz-type
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inhibitor-1
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kunitz
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ttsps
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hemochromatosis
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erythropoiesis
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microcytic
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membrane-anchored
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urokinase-type
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ferroportin
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iron-deficiency
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pro-hgf
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pericellular
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upa
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autoactivation
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two-chain
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hypochromic
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medicine
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protease-activated
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tmprss4
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spint2
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corpuscular
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erythroferrone
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profilaggrin
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camostat
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corin
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epithelial-derived
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par-2
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hypotrichosis
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drug development
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diagnostics
- 3.4.21.109
- hepatocyte
- hepcidin
- hai-1
- anemia
- metastasis
- prostate
- hepsin
- zymogen
- transferrin
- prostasin
- overload
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trypsin-like
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irida
- plasminogen
- hemojuvelin
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iron-refractory
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kunitz-type
- inhibitor-1
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kunitz
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ttsps
- hemochromatosis
-
erythropoiesis
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microcytic
-
membrane-anchored
-
urokinase-type
-
ferroportin
-
iron-deficiency
- pro-hgf
-
pericellular
- upa
-
autoactivation
-
two-chain
-
hypochromic
- medicine
-
protease-activated
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tmprss4
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spint2
-
corpuscular
-
erythroferrone
- profilaggrin
- camostat
- corin
-
epithelial-derived
- par-2
- hypotrichosis
- drug development
- diagnostics
Reaction
cleaves various synthetic substrates with Arg or Lys at the P1 position and prefers small side-chain amino acids, such as Ala and Gly, at the P2 position =
Synonyms
Epi/MTP, epithin, epithin/matriptase, influenza virus-activating protease, matriptase, matriptase-1, matriptase-2, matriptase-3, matriptase1, matriptase1a, membrane-type serine protease 1, membrane-type serine protease 1/matripase, membrane-type serine protease-1, membrane-type serine protease1, membrane-type serine proteinase matripase, membrane-type serine proteinase matriptase, More, MT-2, MT-SP-1, MT-SP1, MT-SP1/matripase, MT2, notopleural, prostamin, PRSS14, r-matripase, serine protease matriptase-2, serine protease SNC19/matripase, SNC19, ST-14, ST14, suppression of tumorigenecity 14, suppressor of tumorigenicity 14, suppressor of tumorigenicity 14 protein, suppressor of tumorigenicity-14, TADG-15, TADG15, TMPRSS6, transmembrane serine protease 6, tumor-associated differentially expressed gene-15, tumor-associated type II transmembrane serine protease, type 2 transmembrane serine protease, type II transmembrane protease, type II transmembrane serine protease
ECTree
3.4.21.109 matriptaseAdvanced search results
results (
results (Engineering
Engineering on EC 3.4.21.109 - matriptase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A118D
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mutation causes an intra-molecular structural imbalance that impairs matriptase-2 activation
A757S
site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme
A757S/L785S
site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme
D217A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
D521N
point mutations D521N and E522K located in the conserved D/NXSDE motif in the LDLa2 domain of matriptase-2 are associated with iron-refractory iron deficiency anemia in patients and affect residues predicted to bind Ca2+. In vitro, the D521N and E522K mutants show reduced cell surface localization, increased Golgi retention, impaired autoactivation of matriptase-2, impaired cleavage of hemojuvelin, and impaired ability to repress Hamp1 reporter expression but are able to bind hemojuvelin
D60A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
D799A
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matripase mutant altered in the substrate binding pocket, is able to traffic in the absence of hepatocyte growth factor activator inhibitor-1
D96A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
E169A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
E522K
point mutations D521N and E522K located in the conserved D/NXSDE motif in the LDLa2 domain of matriptase-2 are associated with iron-refractory iron deficiency anemia in patients and affect residues predicted to bind Ca2+. In vitro, the D521N and E522K mutants show reduced cell surface localization, increased Golgi retention, impaired autoactivation of matriptase-2, impaired cleavage of hemojuvelin, and impaired ability to repress Hamp1 reporter expression but are able to bind hemojuvelin
E712Y
site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme
E712Y/A757S/L785S
site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme
F94A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
F97A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
G442R
matriptase-2 containing the point mutation G442R located in the second CUB domain demonstrate impaired autoactivation, are still able to bind but demonstrate reduced cleavage of coexpressed hemojuvelin, and exhibit reduced ability to repress HAMP reporter expression
G827R
H143A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
H665F
site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme
I41A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
I60A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
K224A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
L153A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
L785S
site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme
N164Q/R614A
mutation at activation cleavage site, variant is locked in the zymogen form, about 3% of wild-type activity
N164Q/R614A/S805A
mutation at activatio, plus mutant cleavage site, variant is locked in the zymogen form, plus mutation S805A to prevent unwanted proteolytic degradation during crystallization
N302Q
N485Q
N772Q
N95A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
Q145A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
Q174A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
Q175A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
Q221A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
Q38A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
R222A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
R60A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
R774C
R87A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
S762A
S805A
T150A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
T98A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
Y146A
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site-directed mutagenesis, the mutant shows altered inhibition kinetics with different inhibitors, overview
R599X
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point mutation identified in zorro mice causing premature termination of matriptase-2 and an iron deficiency phenotype
W783X
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point mutation identified in masquerade mice causing premature termination of matriptase-2 and an iron deficiency phenotype
D603-V855
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using CHO-K1 cells, a secreted variant of rat r-matriptase consisting of the of the catalytic domain (and its N-terminal spacer region) (Asp603Val855) L-matriptase is produced. HL-matriptase and L-matriptase are inhibited by purified maHAI-1 with a similar extent when t-butyloxycarbonyl-Gln-Ala-Arg-MCA and acetyl-Lys-Thr-Lys-Gln-Leu-Arg-MCA are were used as substrates
DELTA1-603
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variant in which the catalytic domain and its N-terminal spacer region (Cys604-Val855) are deleted from matriptase: variant indicates that the catalytic domain is critical for the release of the C-terminal fragment from the cell surface
G149N
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mutant G149 fused to Myc-epitope-hexahistidine tag at its carboxyl-terminus. This mutant is impaired with respect to the generation of an N-terminus at Ser-150. When probed with an anti-Myc antibody no signals for matriptase C-terminal fragment is detected
N772Q
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Asn772 is N-glycosylated. Mutant N772Q consisting of the catalytic domain of matriptase bearing a N772Q mutation fused to Myc-epitope-hexahistidine tag at its carboxyl-terminus is not detected in the medium conditioned by transfected cells but is on the cell surface and purified mutant N772Q exhibits markedly reduced activity toward peptide substrate methylsulfonyl-D-cyclohexyltyrosylglycyl-arginine-p-nitroanilide acetate
S805A
Y81-V855
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using CHO-K1 cells, a secreted variant of rat r-matriptase consisting of the entire extracellular domains (Tyr81-Val855) HL-matriptase is produced (variant contains the stem domain). HL-matriptase and L-matriptase are inhibited by purified maHAI-1 with a similar extent when t-butyloxycarbonyl-Gln-Ala-Arg-MCA and acetyl-Lys-Thr-Lys-Gln-Leu-Arg-MCA are were used as substrates. HL-matriptase is inhibited more strongly than L-matriptase by maHAI-1 in the hydrolysis of t-butyloxycarbonyl-[(2S)-2-amino-3-(benzyloxycarbonyl)propionyl]-Pro-Arg-MCA. The stem domain of matriptase facilitates the inhibitory interaction of this protease with maHAI-1 in the hydrolysis of t-butyloxycarbonyl-[(2S)-2-amino-3-(benzyloxycarbonyl)propionyl]-Pro-Arg-MCA
additional information
G827R
a naturally occuring missense mutation in the highly conserved peptidase S1S6 domain, causing autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair, phenotype, overview
G827R
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naturally occurring mutation, the rare congenital human disorder, autosomal recessive ichthyosis with hypotrichosis is linked to homozygosity for a C2672GA mutation located in exon 19 of the ST14 gene, phenotype, overview
G827R
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the mutation in the catalytic domain causes autosomal recessive Ichthyosis with hypotrichosis, the G827R mutant is catalytically inactive and does not perform autoproteolysis due to a blockade of access to the binding/catalytic cleft of the enzyme, molecular modeling, overview, elevated expression levels compared to the wild-type enzyme, the G827R substitution does not impair the ability of the protease to localize at the cell surface
N302Q
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significant resistance to degradation in the N-acetylglucosminyltransferase V transfectants
N485Q
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significant resistance to degradation in the N-acetylglucosminyltransferase V transfectants
N772Q
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completely degraded in the N-acetylglucosminyltransferase V transfectants
R774C
point mutation identified in an iron-refractory iron deficiency anemia patient is located in the protease domain and disrupts accurate C32/C36 or C35/C37 disulfide bonding within the protease domain
S762A
protease dead mutation is shown in vitro to be ineffective in repressing Hamp1 reporter expression
S805A
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matripase mutant altered in the catalytic triad, is able to traffic in the absence of hepatocyte growth factor activator inhibitor-1
S805A
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mutation of a catalytic residue, inactive mutant, elevated expression levels compared to the wild-type enzyme
S805A
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active-site serine is mutated to alanine, no 28 kDa is produced form either medium or cell membrane samples when expressed in COS-1 cells, suggesting that activation cleavage of wild-type-matriptase in COS-1 cells occurs via a mechanism requiring its active site
S805A
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mutant is unable to undergo activation when expressed in MDCK cells
additional information
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enzyme and hepatocyte growth factor activator inhibitor-1, Hai1, deficient phenotype, hai1 mutant defects are rescued by inactivation of matriptase1a, overview
additional information
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generation of the 26 kDa soluble form in matriptase expressing cells is not strictly autocatalytic and may involve other proteases
additional information
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mutations in any of the residues of the catalytic triad render matriptase unable to undergo activation site cleavage, inactivating mutations in the Ca2+-binding motifs of any or all of the four LDLRA domains prevents the activation of matriptase
additional information
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pathogenesis of dysregulated matriptase activity, dysregulated matriptase potently supports epithelial transformation, overview
additional information
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small interfering RNAs for matriptase efficiently block both the matriptase expression and the cleavage of IGBP-rP1 in OVISE cells
additional information
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when implanting enzyme overexpressing Mat-AZ521 cells into nude mice subcutaneously or intraperitoneally, Mat-AZ521 cells grew faster and produced much larger solid tumors than the control cells, overexpression shortened the survival time of tumor-bearing mice, number and the size of blood vessels in tumor tissues are significantly higher in the Mat-AZ521 tumors than in the control cells
additional information
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penta-alanine mutants 2-8 and 7-11 show 4 and 4.5fold enhanced proteolytic activity as compared to the wild type enzyme, respectively
additional information
costruction of enzyme mutants with deletion of first 9 amino acids or the first 46 amino acids
additional information
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siRNA knockdown of the enzyme in MCF-7 cells using three independent non-overlapping synthetic RNA duplexes
additional information
siRNA knockdown of the enzyme in MCF-7 cells using three independent non-overlapping synthetic RNA duplexes
additional information
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genetic ablation of the enzyme in hepatocyte growth factor activator inhibitor-1-deficient embryos restores the integrity of chorionic trophoblasts and enables placental labyrinth formation and development in turn, which otherwise is prevented, overview, phenotype of single enzyme knockout and double enzyme and inhibitor knockout mutant embryos, overview
additional information
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matriptase depletion results in postnatal death of the mice due to dehydration which is caused by a lack of epithelial barrier function in the skin of newborns, these matriptase knockout mice also have abnormal hair follicle development and disturbed thymic homeostasis showing increased lymphocyte apoptosis in the thymuses and profilaggrin accumulation in epidermal tissue, transgenic mice with increased expression of matriptase in the epidermis show induction of spontaneous squamous cell carcinomas and strongly potentiated chemical skin carcinogenesis, possibly through activation of the tumor-promoting PI3K-Akt pathway, while double transgenic mice co-expressing matriptase and its cognate inhibitor HAI-1 do not develop spontaneous skin cancers and do not show increased susceptibility to chemical carcinogenesis
additional information
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matriptase-deficient mice develop normally, but do not survive postnatally owing to an epidermal barrier defect, transgenic mice with a very modest overexpression of matriptase in the skin become remarkably susceptible to carcinogen-induced tumour formation
additional information
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null mice show impaired development of the hair follicles and immune system and are unable to survive 48 hours past birth due to rapid dehydration through an abnormally formed epidermal barrier
additional information
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phenotype of enzyme-deficient mice and pathogenesis of dysregulated matriptase activity, overview, early lethality of ST14 null mice, transgenic mice expressing modest levels of matriptase in basal keratinocytes display progressive epidermal hyperplasia with fibrosis and dermal inflammation, which spontaneously progresses to invasive squamous cell carcinoma
additional information
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a construct consisting of the catalytic domain of matriptase fused to Myc-epitope-hexahistidine tag at its carboxyl-terminus shows comparable kinetic activity to the full-length rat matriptase toward peptide substrate methylsulfonyl-D-cyclohexyltyrosylglycyl-arginine-p-nitroanilide acetate
additional information
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a full-length rat matriptase and a chimera consisting of the cytoplasmic and transmembrane regions of the matriptase and green fluorescent protein (designated as 1-86GFP) are found to localize exclusively to the basolateral membrane domain when expressed in Madin-Darby canine kidney epithelial cells
additional information
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engineered L-Matriptase is a secreted variant of r-matriptase in which the cytosolic, signal anchor, and stem domains (Met1-Asp603) are replaced with the human immunoglobulin kappa-chain signal peptide and S-tag (ST). L-Matriptase is produced in CHO-K1 cells and is converted to an active form via cleavage with recombinant enterokinase
additional information
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four matriptase pseudozymogens containing at least the catalytic domain are constructed. Each plasmid is expressed as His-tagged fusion proteins and contains a site for activation by recombinant enterokinase. Pseudozymogens with His6-tag at their C-termini form multimers linked by intermolecular disulfide bonds. After treatment with r-EK, they exhibit no detectable hydrolytic activity. Designated pseudozymogen His6t-S-CD consisting of a spacer and the catalytical domain with an N-terminal His6-tag is secreted as a monomer. After recombinant enterokinase treatment pseudozymogen His6t-S-CD exhibits enzymatic activity comparable to secreted variant L-matriptase
additional information
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preparation of a matriptase pseudozymogen (HL-matriptase zymogen): secreted variant of matriptase consisting of the entire extracellular domain (Tyr81 to Val855), activation-cleavage sequence (Thr-Lys-Gln-Ala-Arg614) is replaced with the enterokinase recognition sequence (Asp-Asp-Asp-Asp-Lys). Pseudozymogen is converted to HL-matriptase enzyme (activated) by incubation with enterokinase. Pseudozymogen exhibits optimal activity toward substrate acetyl-Lys-Thr-Lys-Gln-Leu-Arg-methyl-coumaryl-7-amide at pH 6.0 (mildly acidic). Substrate hydrolysis at pH 6.0 with 145 mM NaCl is inhibited. In a buffer of pH 6.0 containing 5 mM NaCl (low ionic strength), the activity of pseudozymogen is only 30times lower than that of the respective two-chain form (activated form after enterokinase treatment). This finding indicates that the in vivo activation of matriptase occurs via a mechanism involving the activity of zymogen
