Information on EC 3.4.21.B10 - neurosin

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.B10
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
neurosin
-
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
149565-66-2
-
9001-01-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Balb/c mice
-
-
Manually annotated by BRENDA team
infected with Theiler's murine encephalomyelitis virus, gene Klk6
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
the enzyme is a member of the human kallikrein gene family of secreted serine proteases
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha-synuclein + H2O
?
show the reaction diagram
-
neurosin may degrade alpha-synuclein, a major component of the Lewy bodies commonly observed in dopaminergic neurons of patients with sporadic Parkinsons disease
-
-
?
alpha1-Antichymotrypsin + H2O
?
show the reaction diagram
-
hydrolysis of the FRET peptide derived from alpha1-antichymotrypsin
-
-
?
amyloid precursor proteins + H2O
?
show the reaction diagram
benzoyl-L-Arg-7-amido-4-methylcoumarin + H2O
benzoyl-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-FR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-FR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Gln-L-Ala-L-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-Gln-L-Ala-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-LR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-LR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
Gelatin + H2O
?
show the reaction diagram
-
-
-
-
?
myelin basic protein + H2O
?
show the reaction diagram
N-alpha-tert-butyloxycarbonyl-Gln-Ala-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Gln-Ala-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-alpha-tert-butyloxycarbonyl-Phe-Ser-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Phe-Ser-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-L-Arg + H2O
benzoic acid + L-Arg
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
best synthetic substrate
-
-
?
o-aminobenzoic acid-AFRLAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-AFRVGQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-EEHAFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-EELAFKFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-EEQNKLVH-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
low rates of hydrolysis of the pro-peptide substrate by KLK6
-
-
?
o-aminobenzoic acid-EHSAFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoic acid-NLRQRESS-[2,4-dinitrophenyl]ethylenediamine + H2O
?
show the reaction diagram
-
autolysis loop substrate is hydrolyzed with 2-3 order of magnitude greater efficiency than the pro-peptide substrate
-
-
?
peptide + H2O
?
show the reaction diagram
-
phage-display analysis using optimum hydrolysis conditions reveals a potential cleavage motif for recombinant human KLK6: W(G/T)-A(K)-R(K)-/-(R/K)-A(R/S)-W(G/F). The preferred P1-P19 scissile bond appears to be a dibasic arginine-arginine/arginine-lysine/lysine-arginine doublet
-
-
?
Phe-Ser-Arg-7-amido-4-methylcoumarin
Phe-Ser-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
purified hK6
-
-
?
plasminogen + H2O
?
show the reaction diagram
polypeptide + H2O
peptides
show the reaction diagram
-
-
?
precursor of the Abeta amyloid peptid + H2O
?
show the reaction diagram
-
hydrolysis of the FRET peptide derived from human precursor of the Abeta amyloid peptide
-
-
?
pro-KLK6 + H2O
?
show the reaction diagram
-
KLK6 hydrolyzes its pro-sequence and internal autolysis site. Ability of KLK6 to activate pro-KLK6 is essentially negligible when compared to the rate of the internal autolytic inactivation or to the ability of other proteases to activate pro-KLK6
-
-
?
Pro-Phe-Arg-7-amido-4-methylcoumarin
Pro-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
purified hK6
-
-
?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
show the reaction diagram
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
show the reaction diagram
proteinase-activated receptor 1 + H2O
?
show the reaction diagram
-
main cleavage site: NATLDPR-/-SFLLRNPNDKYE
-
-
?
proteinase-activated receptor 2 + H2O
?
show the reaction diagram
-
main cleavage site: GTNRSSKGR-/-SLIGKVDGTSHVTGKGVT
-
-
?
proteinase-activated receptor 4 + H2O
?
show the reaction diagram
-
main cleavage site: GDDSTPSILPAPR-/-GYPGOV
-
-
?
Val-Pro-Arg-7-amido-4-methylcoumarin
Val-Pro-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
purified hK6
-
-
?
WAAFRFSQA + H2O
WAAFR + FSQA
show the reaction diagram
-
-
-
-
?
WEAFRSSDQ + H2O
WEAFR + SSDQ
show the reaction diagram
-
-
-
-
?
WEAVRSAMW + H2O
WEAVR + SAMW
show the reaction diagram
-
-
-
-
?
WIGFRNAGA + H2O
WIGFR + NAGA
show the reaction diagram
-
-
-
-
?
WTAFRSAYG + H2O
WTAFR + SAYG
show the reaction diagram
-
-
-
-
?
WYMTRSAMG + H2O
WYMTR + SAMG
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
amyloid precursor proteins + H2O
?
show the reaction diagram
Q92876
enzyme may play a role in development of Alzheimer's disease
-
-
?
plasminogen + H2O
?
show the reaction diagram
-
the enzyme is regulated by an autoactivation/autoinactivation mechanism. Mature hK67 displays a trypsin-like activity against human plasminogen, the putative physiological substrate
-
-
?
polypeptide + H2O
peptides
show the reaction diagram
Q92876
-
-
?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
show the reaction diagram
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-benzyl 1-[3-[(benzyloxy)carbonyl]phenyl] (2S,3S)-3-(4-hydroxybenzyl)-4-oxoazetidine-1,2-dicarboxylate
-
-
2-[5-(5-carbamimidoyl-1H-benzimidazol-2-yl)-3'-carbamoyl-6-hydroxybiphenyl-3-yl]butanedioic acid
-
-
2-[[4-(aminomethyl)phenyl]carbamoyl]-1-[(1-benzyl-1H-imidazol-2-yl)methyl]-3-hydroxypyridinium
-
crystal structure analysis of enzyme bound to inhibitor 2-[[4-(aminomethyl)phenyl]carbamoyl]-1-[(1-benzyl-1H-imidazol-2-yl)methyl]-3-hydroxypyridinium, two adjacent beta-barrels connected with several alpha helices and turns, overview
3-[[N-[[4-(aminomethyl)cyclohexyl]carbonyl]-O-(pyrimidin-2-yl)tyrosyl]amino]benzoic acid
-
-
4,4'-[benzene-1,4-diylbis(methanediyloxy)]bis(3-iodobenzenecarboximidamide)
-
-
4,4'-[pentane-1,5-diylbis(oxy)]bis(3,5-dibromobenzenecarboximidamide)
-
-
4-amino-N-[4-(aminomethyl)phenyl]-2-hydroxybenzamide
-
-
alpha2-Macroglobulin
-
-
-
antipain
-
-
antithrombin III
-
most efficient endogenous inhibitor
-
Aprotinin
Bovine pancreatic trypsin inhibitor
-
weak
-
Bowman-Birk inhibitor
-
weak
C1-inhibitor
-
-
-
Ca2+
-
0.005 mM completely inhibits hK6 at pH 7.5 or 9.0
K+
-
inhibits hK6 at pH 7.5 or 9.0
leupeptin
-
-
Mg2+
-
0.005 mM completely inhibits hK6 at pH 7.5 or 9.0
N-[4-(aminomethyl)phenyl]-2-hydroxy-3-methoxybenzamide
-
-
N-[4-(aminomethyl)phenyl]-2-hydroxy-4-methoxybenzamide
-
-
N-[4-(aminomethyl)phenyl]-3-chloro-2-hydroxybenzamide
-
-
N-[4-(aminomethyl)phenyl]-3-[(1-benzyl-1H-imidazol-2-yl)methoxy]pyridine-2-carboxamide
-
-
N-[4-(aminomethyl)phenyl]-4-(dimethylamino)-2-hydroxybenzamide
-
-
N-[4-(aminomethyl)phenyl]-4-chloro-2-hydroxybenzamide
-
-
N-[4-(aminomethyl)phenyl]-4-ethoxy-2-hydroxybenzamide
-
-
N-[4-(aminomethyl)phenyl]-5-tert-butyl-2-hydroxybenzamide
-
-
NH4+
-
inhibits hK6 at pH 7.5 or 9.0
PMSF
-
-
RNAi
-
suppression of protease M, causes a decrease in myelin basic protein mRNA in cultured oligodendrocytes
-
Sodium citrate
-
inhibits the enzyme at pH 9.0
Sodium sulfate
-
inhibits the enzyme at pH 9.0
Soybean trypsin inhibitor
-
[(4R,7R,10R,13S,16S)-10-(4-aminobutyl)-18-(benzyloxy)-13,16-bis(hydroxymethyl)-2-methyl-7-(2-methylpropyl)-6,9,12,15,18-pentaoxooctadecan-4-yl]boronic acid
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2'-deoxy-5-azacytidine
-
can reactivate KLK6 in non-expressing breast cancer cells. Induces KLK6 expression in cell lines MDA-MB-435P, BT-474, MCF-7, and ZR-75-1 and significantly increases synthesis of hK6 protein. Results in a 2fold increase in KLK6 mRNA and protein levels in HMECs. Combined 5-aza-29-deoxycytidine/trichostatin A treatment results in synergistic activation of KLK6 in MDA-MB-231 cells
androgens
-
slight up-regulation
-
caveolin-1
-
mediates both KLK6 gene expression and protein secretion
-
chondroitin sulfate
-
activates hK6 in a concentration-dependent manner
dermatan sulfate
-
activates hK6 in a concentration-dependent manner
EB1089
-
vitamin D3 analog EB1089 can restore KLK6 expression in T47D cells
estrogen
-
up-regulaion
heparan sulfate
-
activates hK6 in a concentration-dependent manner
heparin
-
activates hK6 in a concentration-dependent manner
progestins
-
up-regulaion
Sodium citrate
-
reveals greatest activity at pH 7.5
Sodium sulfate
-
reveals greatest activity at pH 7.5
trichostatin A
-
moderately induces KLK6 in MDA-MB-231 cells. Combined 5-aza-29-deoxycytidine/trichostatin A treatment results in synergistic activation of KLK6 in MDA-MB-231 cells
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3
benzoyl-L-Arg-7-amido-4-methylcoumarin
-
-
0.0003
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.0003 - 0.009
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
0.0011
o-aminobenzoic acid-AFRLAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.001
o-aminobenzoic acid-AFRVGQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.0014
o-aminobenzoic acid-EEHAFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.0016
o-aminobenzoic acid-EHSAFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.0028 - 0.004
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine
0.3
Phe-Ser-Arg-7-amido-4-methylcoumarin
-
purified hK6
0.23
Pro-Phe-Arg-7-amido-4-methylcoumarin
-
purified hK6
0.36
Val-Pro-Arg-7-amido-4-methylcoumarin
-
purified hK6
0.062
WAAFRFSQA
-
pH 7.5, 37C
0.249
WEAFRSSDQ
-
pH 7.5, 37C
0.092
WEAVRSAMW
-
pH 7.5, 37C
0.182
WIGFRNAGA
-
pH 7.5, 37C
0.336
WTAFRSAYG
-
pH 7.5, 37C
0.069
WYMTRSAMG
-
pH 7.5, 37C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7.1
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
Homo sapiens
-
at pH 7.5, in the presence 2 M sodium citrate
0.4 - 11.6
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
9.2
o-aminobenzoic acid-AFRLAQ-N-[2,4-dinitrophenyl]ethylenediamine
Homo sapiens
-
at pH 7.5, in the presence 2 M sodium citrate
2.7
o-aminobenzoic acid-AFRVGQ-N-[2,4-dinitrophenyl]ethylenediamine
Homo sapiens
-
at pH 7.5, in the presence 2 M sodium citrate
7.1
o-aminobenzoic acid-EEHAFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
Homo sapiens
-
at pH 7.5, in the presence 2 M sodium citrate
9.1
o-aminobenzoic acid-EHSAFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
Homo sapiens
-
at pH 7.5, in the presence 2 M sodium citrate
2.3 - 14.2
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine
0.00083
Phe-Ser-Arg-7-amido-4-methylcoumarin
Homo sapiens
-
purified hK6
0.0003
Pro-Phe-Arg-7-amido-4-methylcoumarin
Homo sapiens
-
purified hK6
0.0013
Val-Pro-Arg-7-amido-4-methylcoumarin
Homo sapiens
-
purified hK6
0.9
WAAFRFSQA
Homo sapiens
-
pH 7.5, 37C
1.2
WEAFRSSDQ
Homo sapiens
-
pH 7.5, 37C
2
WEAVRSAMW
Homo sapiens
-
pH 7.5, 37C
1.7
WIGFRNAGA
Homo sapiens
-
pH 7.5, 37C
3.8
WTAFRSAYG
Homo sapiens
-
pH 7.5, 37C
1.4
WYMTRSAMG
Homo sapiens
-
pH 7.5, 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0018
2-[[4-(aminomethyl)phenyl]carbamoyl]-1-[(1-benzyl-1H-imidazol-2-yl)methyl]-3-hydroxypyridinium
Homo sapiens
-
pH and temperature not specified in the publication
0.0038
4-amino-N-[4-(aminomethyl)phenyl]-2-hydroxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0086
N-[4-(aminomethyl)phenyl]-2-hydroxy-3-methoxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0206
N-[4-(aminomethyl)phenyl]-2-hydroxy-4-methoxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0135
N-[4-(aminomethyl)phenyl]-3-chloro-2-hydroxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0018
N-[4-(aminomethyl)phenyl]-3-[(1-benzyl-1H-imidazol-2-yl)methoxy]pyridine-2-carboxamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0106
N-[4-(aminomethyl)phenyl]-4-(dimethylamino)-2-hydroxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0078
N-[4-(aminomethyl)phenyl]-4-chloro-2-hydroxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0129
N-[4-(aminomethyl)phenyl]-4-ethoxy-2-hydroxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0003
N-[4-(aminomethyl)phenyl]-5-tert-butyl-2-hydroxybenzamide
Homo sapiens
-
pH and temperature not specified in the publication
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8
-
at pH 6.0 the rate of hydrolysis of the autolysis loop substrate decreases 2fold, whereas the rate of hydrolysis of the pro-peptide substrate by KLK6 increases approximately 5fold, in comparison to pH 8.0. Autolysis loop substrate is still hydrolyzed with 2-3 order of magnitude greater efficiency in comparison to the pro-peptide substrate in this pH-range
7 - 9
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
low enzyme expression
Manually annotated by BRENDA team
-
primary cell culture
Manually annotated by BRENDA team
-
highly down-regulated at metastatic breast cancer sites; up-regulated in primary tumors
Manually annotated by BRENDA team
-
breast carcinoma cell line, enzyme is up-regulated by estrogens, progestin and slightly by androgen
Manually annotated by BRENDA team
-
present as the proenzyme
Manually annotated by BRENDA team
-
quantitative real-time PCR enzyme expression analysis
Manually annotated by BRENDA team
-
quantitative real-time PCR enzyme expression analysis
Manually annotated by BRENDA team
-
grade II
Manually annotated by BRENDA team
-
Barrett esophagus with and without dysplasia
Manually annotated by BRENDA team
-
barely expresses KLK6
Manually annotated by BRENDA team
-
73 intracranial tumor samples are screened for enzyme expression by quantitative real-time PCR analysis, overview
Manually annotated by BRENDA team
-
primary tissue culture
Manually annotated by BRENDA team
-
splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate
Manually annotated by BRENDA team
-
MCF-7 cells with low metastatic potential express KLK6 mRNA and protein levels comparable to normal human mammary epithelial cells
Manually annotated by BRENDA team
-
under resting conditions, Neu 7 astrocytes exhibit a high basal level of stellation, protease activated receptors PAR1 and PAR2 cause a significant reversal of astrocyte stellation
Manually annotated by BRENDA team
-
up-regulated in primary tumors
Manually annotated by BRENDA team
-
splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate
Manually annotated by BRENDA team
-
expression of hK6 is downregulated in comparison with normal salivary gland tissue
Manually annotated by BRENDA team
-
very low enzyme expression
Manually annotated by BRENDA team
-
KLK6 is upregulated
Manually annotated by BRENDA team
-
strong expression in stromal cells located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
heterologous expression of pre-pro-neurosin is localized to the endoplasmic reticulum, intracellular neurosin has no protease activity
Manually annotated by BRENDA team
-
KRP/hK6 is nuclear in glial cells of the brain
Manually annotated by BRENDA team
-
KLK6 localizes to caveolin-1-containing membrane fractions in the presence, but not the absence of caveolin-1
Manually annotated by BRENDA team
additional information
-
the enzyme expression shows a granular cytoplasmic pattern of staining with luminal accentuation, immunohistochemic analysis, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24000
-
calculated from amino acid sequence
25866
-
x * 25866, SDS-PAGE
30000
-
purified hK6, Western blot analysis
31000
-
x * 43000, glycosylated enzyme, SDS-PAGE, x * 31000, deglycosylated enzyme, SDS-PAGE
32000
-
SDS-PAGE
43000
-
x * 43000, glycosylated enzyme, SDS-PAGE, x * 31000, deglycosylated enzyme, SDS-PAGE
additional information
-
the KLK6 gene encodes for various isoforms produced by the utilization of intronic sequences and alternative promoters with multiple transcriptional start sites (transcript variants) or by splicing out coding exons (splice variants). Transcripts encoding full-length hK6 protein are the predominant mRNA species in normal and tumor cells. KLK6 transcript variants 1, 2 and 3, all encode for full-length hK6 protein
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified enzyme bound to inhibitor 9b, X-ray diffraction structure determination and analysis at 1.68 A resolution
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by metal affinity resin
-
by sequential affinity chromatography utilizing Ni-NTA
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hK6 purified on immunoaffinity columns, followed by reverse-phase high performance liquid chromatography, to homogeneity
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nickel-nitrilotriacetic acid-Sepharose column chromatography and benzamidine-Sepharose column chromatography
recombinant
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed from a baculovirus/insect cell line system
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expressed in a baculovirus/insect system
expressed in Escherichia coli M15(pREP4) cells
expressed in HEK-293T cells
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gene encodes for multiple transcript variants
gene KLK6 encoding kallikrein-related peptidase 6 is located within the kallikrein gene cluster containing 15 kallikrein genes that share homology at the DNA-amino acid level and five pseudogenes on chromosome 19q13
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gene KLK6, genetic organization and structure of the kallikrein gene family, clustered on chromosome 19q13.3-q13.4
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gene Klk6, quantitative enzyme expression analysis
gene KLK6, quantitative real-time PCR expression analysis
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into pPUR-tRNA plasmid and transfected into primary oligodendrocytes
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KLK6 genomic region from -80 to +244 relative to the P1 transcriptional start site cloned upstream from the CAT reporter gene. PBLCAT6 (-80,+244) construct and two deletion constructs, pBLCAT6 (-80,+179) and pBLCAT6(-80,+12), transfected into MCF-7 cells
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OV-MZ-6 ovarian cancer cells stably co-transfected with pRc/RSV-plasmid expressing hK4, hK5, hK6, and hK7. Overexpression in OV-MZ-6 ovarian cancer cells and in the peritoneum of nude mice, inoculated with OV-KLK4+5+6+7 cells
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pcDNA3.1-KLK6-Myc/His vector expressed in HEK-293 cells
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pcDNA3.1-Klk6-Myc/His-tagged fusion protein expressed in the mouse keratinocyte cell line MCA3D
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quantitative PCR-based enzyme expression analysis
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quantitative real-time PCR expression analysis
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recombinant KLK6 expressed from an insect cell/baculovirus host. Pro-KLK6 expressed as a fusion construct with a C-terminal Strep-tag and 8x His-tag, respectively in HEK-293 cells
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the precursor form of human kallikrein 6 is overexpressed in Pichia pastoris and is autoprocessed to an active but unstable mature enzyme that subsequently yields the inactive, self-cleavage product, hK6(D81-K244)
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
injury-induced elevations in enzyme level
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Klk6 RNA is up-regulated in splenocytes in a viral capsid protein dependent fashion, using recombinnatly expressed encoding Theiler's murine encephalomyelitis virus TMEV VP1 and VP2 capsid proteins, and in THP-1 monocytes activated by phorbol 12-myristate-13-acetate and lipopolysaccharide
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no change in KLK6 expression is observed upon treatment of T47D cells with trichostatin A
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SJL mice infecteion with Theiler's murine encephalomyelitis virus causes an increase in enzyme expression in the spinal cord and in splenocytes. Klk6 RNA is up-regulated in splenocytes in a viral capsid protein dependent fashion, using recombinnatly expressed encodingTMEVVP1 andVP2 capsid proteins, and in THP-1 monocytes activated by phorbol 12-myristate-13-acetate and lipopolysaccharide
stepwise expression increase from metaplasia to dysplasia and invasive tumors, significantly increased enzyme expression in early invasive cancer, overview
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the enzyme is up-regulated in ovarian cancer
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treatment of MDA-MB-231 and T47D breast tumor cell lines with 5-aza-2'-deoxycytidine results in significant induction of KLK6 expression
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R80Q
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mutation stabilizes the activity of the mature enzyme
S197A
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mutation results in complete loss of hK6 proteolytic activity
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
additional information
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hK6 is involved in normal myelin turnover/demyelination processes, but it is unlikely to self-activate. Possibly it modulates ionotropic glutamate receptors and activates PAR 2