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Information on EC 3.4.21.B10 - neurosin
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3.4.21.B10 neurosinSpecify your search results
Word Map
- 3.4.21.B10
- kallikreins
-
trypsin-like
- medicine
- klk8
- par1
- diagnostics
-
immunofluorometric
The enzyme appears in viruses and cellular organisms
Synonyms
kallikrein 6, neurosin, kallikrein-related peptidase 6, kallikrein-6, serine protease 9, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
hK6
kallikrein 6
kallikrein-6
kallikrein-related peptidase 6
KLK6
neurosin
protease M
S01.236
-
-
-
-
hK6
displays a trypsin-like specificity with strong preference for P1-Arg
kallikrein 6
-
-
-
-
kallikrein 6
-
kallikrein-related peptidase 6
-
KLK6
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic cleavage of polypeptides
substrate binding pocket contains an Asp residue
proteolytic cleavage of polypeptides
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
149565-66-2
-
9001-01-8
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Abz-Ala-Pro-Ala-Asn-Arg-Ser-Arg-Arg-Gly-Val-Ser-Glu-Thr-Gln-EDDnp + H2O
Abz-Ala-Pro-Ala-Asn-Arg-Ser-Arg + Arg-Gly-Val-Ser-Glu-Thr-Gln-EDDnp
-
-
-
?
Abz-Arg-Thr-Ser-Arg-Arg-Lys-Arg-Tyr-Ala-Glu-His-Lys-Gln-EDDnp + H2O
Abz-Arg-Thr-Ser-Arg-Arg-Lys-Arg + Tyr-Ala-Glu-His-Lys-Gln-EDDnp
-
-
-
?
Abz-Asp-Met-Ser-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Ser-Leu-Lys-Arg-Ser-Gln-EDDnp + H2O
?
cleavage sites: Abz-Asp-Met-Ser-Lys-Arg-/-Tyr-Gly-Gly-Phe-Met-Arg-/-Ser-Leu-Lys-Arg-Ser-Gln-EDDnp
-
-
?
Abz-Asp-Tyr-Gln-Lys-Arg-Tyr-Gly-Gly-Phe-Leu-Lys-Arg-Phe-Ala-Glu-Ala-Leu-Gln-EDDnp + H2O
?
cleavage sites: Abz-Asp-Tyr-Gln-Lys-Arg-/-Tyr-Gly-Gly-Phe-Leu-Lys-Arg-/-Phe-Ala-Glu-Ala-Leu-Gln-EDDnp
-
-
?
Abz-Glu-Glu-Val-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu-Lys-Arg-Ser-Gln-EDDnp + H2O
?
cleavage sites: Abz-Glu-Glu-Val-Lys-Arg-/-Tyr-Gly-Gly-Phe-Met-Arg-/-Gly-Leu-Lys-Arg-Ser-Gln-EDDnp
-
-
?
Abz-Leu-Leu-Ala-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Gln-EDDnp + H2O
?
cleavage sites: Abz-Leu-Leu-Ala-Lys-Arg-/-Tyr-Gly-Gly-Phe-Met-Lys-Arg-/-Tyr-Gly-Gly-Phe-Met-Lys-/-Lys-Met-Asp-Glu-Gln-EDDnp
-
-
?
Abz-Lys-Arg-Arg-Ser-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Arg-Arg + Ser-Ser-Lys-Gln-EDDnp
-
-
-
?
Abz-Lys-Leu-Arg-Arg-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Leu-Arg + Arg-Ser-Lys-Gln-EDDnp + Abz-Lys-Leu-Arg-Arg + Ser-Lys-Gln-EDDnp
-
-
-
?
Abz-Lys-Leu-Arg-Ser-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Leu-Arg + Ser-Ser-Lys-Gln-EDDnp
-
-
-
?
Abz-Lys-Lys-Arg-Ser-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Lys-Arg + Ser-Ser-Lys-Gln-EDDnp
-
-
-
?
Abz-Ser-Met-Arg-Val-Arg-Arg-His-Ser-Asp-Pro-Ala-Gln-EDDnp + H2O
Abz-Ser-Met-Arg-Val-Arg + Arg-His-Ser-Asp-Pro-Ala-Gln-EDDnp
-
-
-
?
Abz-Thr-His-Arg-Ser-Lys-Arg-Ser-Ser-Ser-His-Pro-Ile-Gln-EDDnp + H2O
Abz-Thr-His-Arg-Ser-Lys-Arg + Ser-Ser-Ser-His-Pro-Ile-Gln-EDDnp
-
-
-
?
alpha1-Antichymotrypsin + H2O
?
-
hydrolysis of the FRET peptide derived from alpha1-antichymotrypsin
-
-
?
benzoyl-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
benzoyl-Ala-Arg + Arg-7-amido-4-carbamoylmethylcoumarin
-
-
-
?
benzoyl-Ala-Lys-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
benzoyl-Ala-Lys + Arg-7-amido-4-carbamoylmethylcoumarin
-
-
-
?
benzoyl-Ala-Phe-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
benzoyl-Ala-Phe + Arg-7-amido-4-carbamoylmethylcoumarin
-
-
-
?
benzoyl-L-Arg-7-amido-4-methylcoumarin + H2O
benzoyl-L-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
benzoyl-Arg + Arg-7-amido-4-methylcoumarin
-
-
-
?
benzyloxycarbonyl-FR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-FR + 7-amino-4-methylcoumarin
-
-
-
?
benzyloxycarbonyl-L-Gln-L-Ala-L-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-Gln-L-Ala-L-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-LR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-LR + 7-amino-4-methylcoumarin
-
-
-
?
Lys-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
Lys-Ala-Arg + Arg-7-amido-4-carbamoylmethylcoumarin
-
-
-
?
N-alpha-tert-butyloxycarbonyl-Gln-Ala-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Gln-Ala-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
N-alpha-tert-butyloxycarbonyl-Phe-Ser-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Phe-Ser-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
best synthetic substrate
-
-
?
o-aminobenzoic acid-AFRLAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-AFRVGQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-EEHAFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-EELAFKFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-EEQNKLVH-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
low rates of hydrolysis of the pro-peptide substrate by KLK6
-
-
?
o-aminobenzoic acid-EHSAFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
-
-
-
?
o-aminobenzoic acid-NLRQRESS-[2,4-dinitrophenyl]ethylenediamine + H2O
?
-
autolysis loop substrate is hydrolyzed with 2-3 order of magnitude greater efficiency than the pro-peptide substrate
-
-
?
peptide + H2O
?
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
-
purified hK6
-
-
?
precursor of the Abeta amyloid peptid + H2O
?
-
hydrolysis of the FRET peptide derived from human precursor of the Abeta amyloid peptide
-
-
?
pro-KLK6 + H2O
?
-
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
-
purified hK6
-
-
?
proteinase-activated receptor 1 + H2O
?
main cleavage site: NATLDPR-/-SFLLRNPNDKYE
-
-
?
proteinase-activated receptor 2 + H2O
?
main cleavage site: GTNRSSKGR-/-SLIGKVDGTSHVTGKGVT
-
-
?
proteinase-activated receptor 4 + H2O
?
main cleavage site: GDDSTPSILPAPR-/-GYPGOV
-
-
?
Val-Pro-Arg-7-amido-4-methylcoumarin
Val-Pro-Arg + 7-amino-4-methylcoumarin
-
purified hK6
-
-
?
alpha-synuclein + H2O
?
-
neurosin may degrade alpha-synuclein, a major component of the Lewy bodies commonly observed in dopaminergic neurons of patients with sporadic Parkinsons disease
-
-
?
alpha-synuclein + H2O
?
recombinant and naturally secreted KLK6 can readily cleave alpha-synuclein fibrils that have the potential for cell-to-cell propagation in a prion-like mechanism
-
-
?
alpha-synuclein + H2O
?
the enzyme cleaves human monomeric and mouse fibrilar alpha-synuclein, leading to the appearance of proteolytic peptide fragments below 15 kDa
-
-
?
amyloid precursor proteins + H2O
?
enzyme may play a role in development of Alzheimer's disease
-
-
?
myelin basic protein + H2O
?
-
hydrolysis of the FRET peptide derived from human myelin basic protein
-
-
?
myelin basic protein + H2O
?
-
close relationship between protease M and myelin proteins
-
-
?
myelin basic protein + H2O
?
-
close relationship between protease M and myelin proteins
-
-
?
plasminogen + H2O
?
-
the enzyme is regulated by an autoactivation/autoinactivation mechanism. Mature hK67 displays a trypsin-like activity against human plasminogen, the putative physiological substrate
-
-
?
plasminogen + H2O
?
-
hydrolysis of the FRET peptide derived from plasminogen
-
-
?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
-
-
-
-
?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
-
-
-
-
?
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
-
-
-
-
?
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
-
-
-
-
?
additional information
?
-
enzyme is involved in breast and ovarian cancer
-
-
?
additional information
?
-
-
hK6 does not hydrolyze the Nalpha-tosyl-L-Arg methyl ester
-
-
?
additional information
?
-
-
hK6 shows weak trypsin-like enzymatic activity, does not cleave Val-Leu-Lys-7-amido-4-methylcoumarin, Glu-Lys-Lys-7-amido-4-methylcoumarin and Ala-Ala-Pro-Phe-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
hydrolysis of the FRET peptide series o-aminobenzoic acid-XLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine, o-aminobenzoic acid-KXRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine, o-aminobenzoic acid-KLRXSKQ-N-[2,4-dinitrophenyl]ethylenediamine, o-aminobenzoic acid-KLRSXKQ-N-[2,4-dinitrophenyl]ethylenediamine and FRET peptide derived from hK6 maturation/inactivation cleavage site or PAR. o-aminobenzoic acid-AFKFAQ-N-[2,4-dinitrophenyl]ethylenediamine, o-aminobenzoic acid-VLFEKKVYLQ-N-[2,4-dinitrophenyl]ethylenediamine and o-aminobenzoic acid-GTEASVVAPQ-N-[2,4-dinitrophenyl]ethylenediamine are not hydrolyzed
-
-
?
additional information
?
-
strong preference for P1-Arg over Lys, which is accepted nearly equally as well as Ala, Met, and Nle
-
-
?
additional information
?
-
KLK6 displays trypsin-like activity, with the P1 position occupied only by Arg and a strong preference for Ser in P1'. Increased frequency of Val or Phe at the P2 position, whereas Ala is strongly preferred at the P2' position. Cleaves peptides derived from human myelin protein and Abeta amyloid peptide
-
-
?
additional information
?
-
-
marked preference for Arg over Lys at position P1. Ala and Met are slightly more preferred at position P1 residues than Lys. Strong specificity for Arg and Lys at the P2 position. Activation cleavage site: EQNK-LVHG
-
-
?
additional information
?
-
marked preference for Arg over Lys at position P1. Ala and Met are slightly more preferred at position P1 residues than Lys. Strong specificity for Arg and Lys at the P2 position. Activation cleavage site: EQNK-LVHG
-
-
?
additional information
?
-
-
the enzyme activates G-protein coupled protease activated receptors
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
amyloid precursor proteins + H2O
?
enzyme may play a role in development of Alzheimer's disease
-
-
?
plasminogen + H2O
?
-
the enzyme is regulated by an autoactivation/autoinactivation mechanism. Mature hK67 displays a trypsin-like activity against human plasminogen, the putative physiological substrate
-
-
?
alpha-synuclein + H2O
?
recombinant and naturally secreted KLK6 can readily cleave alpha-synuclein fibrils that have the potential for cell-to-cell propagation in a prion-like mechanism
-
-
?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
-
-
-
-
?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
-
-
-
-
?
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
-
-
-
-
?
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
-
-
-
-
?
additional information
?
-
enzyme is involved in breast and ovarian cancer
-
-
?
additional information
?
-
-
the enzyme activates G-protein coupled protease activated receptors
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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)
-
amyloid precursor protein Kunitz protease inhibitor domain
combinatorial approach to engineering KLK6 inhibitors via flow cytometry-based screening of a yeast-displayed mutant library of the human amyloid precursor protein Kunitz protease inhibitor domain (APPI). On the basis of this screening, APPI(M17L/I18F/S19F/F34V) (APPI-4M) is generated, an APPI variant with a KLK6 inhibition constant (Ki) of 160 pM and a turnover time of 10 days. APPI-4M is a potent KLK6 inhibitor, displaying 146fold improved affinity and 13fold improved proteolytic stability compared with wild-type APPI (APPIWT). It is demonstrated that APPI-4M acts as a functional inhibitor in a cell-based model of KLK6-dependent breast cancer invasion
-
APPI-4M
combinatorial approach to engineering KLK6 inhibitors via flow cytometry-based screening of a yeast-displayed mutant library of the human amyloid precursor protein Kunitz protease inhibitor domain (APPI). On the basis of this screening, APPI(M17L/I18F/S19F/F34V) (APPI-4M) is generated, an APPI variant with a KLK6 inhibition constant (Ki) of 160 pM and a turnover time of 10 days. APPI-4M is a potent KLK6 inhibitor, displaying 146fold improved affinity and 13fold improved proteolytic stability compared with wild-type APPI (APPIWT). It is demonstrated that APPI-4M acts as a functional inhibitor in a cell-based model of KLK6-dependent breast cancer invasion
-
N-[4-(aminomethyl)phenyl]-3-[(1-benzyl-1H-imidazol-2-yl)methoxy]pyridine-2-carboxamide
-
RNAi
-
suppression of protease M, causes a decrease in myelin basic protein mRNA in cultured oligodendrocytes
-
[(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
-
self-regulating activity of KLK6 is negative feedback inhibition via autolytic inactivation
-
additional information
-
KLK6 secretion is reduced by nearly half in the presence of constitutively active SRC531. Pharmacological inhibition of AKT leads to reduced KLK6 expression and KLK6 secretion
-
additional information
-
activity of hK6 can be suppressed by ca. 60% by monoclonal antibody E24
-
additional information
enzyme inhibitors with a para-amidobenzylanmine P1 group and a 2-hydroxybenzamide scaffold linker identified through virtual screening, The tertiary folding of the enzyme complexed with the inhibitor, overview
-
additional information
-
enzyme inhibitors with a para-amidobenzylanmine P1 group and a 2-hydroxybenzamide scaffold linker identified through virtual screening, The tertiary folding of the enzyme complexed with the inhibitor, overview
-
additional information
Klk6-neutralizing antibodies diminish spinal cord inflammation and demyelination to early chronic phases of disease
-
additional information
-
expression of protease M mRNA and protein is rapidly reduced in demyelination
-
additional information
-
Klk6-neutralizing antibodies diminish spinal cord inflammation and demyelination to early chronic phases of disease
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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
EB1089
vitamin D3 analog EB1089 can restore KLK6 expression in T47D cells
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
-
self-regulating activity of KLK6 is negative feedback inhibition via autolytic inactivation. Activation of pro-KLK6 may be achieved through the action of a separate activating protease (possibly plasmin or KLK5)
-
additional information
the steroid hormones estradiol, aldosterone, dihydrotestosterone, dexamethasone and norgestrol do not significantly change KLK6 expression in ovarian cancer cell lines
-
additional information
-
the steroid hormones estradiol, aldosterone, dihydrotestosterone, dexamethasone and norgestrol do not significantly change KLK6 expression in ovarian cancer cell lines
-
additional information
-
expression of protease M is increased in GST-pi-positive oligodendrocytes during remyelination. After tumor necrosis factor-alpha and IFN-gamma stimulation colocalization of protease M and myelin basic protein in the oligodendroglial process
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
Abz-Arg-Thr-Ser-Arg-Arg-Lys-Arg-Tyr-Ala-Glu-His-Lys-Gln-EDDnp
pH 7.5, 37°C
0.0018
Abz-Asp-Met-Ser-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Ser-Leu-Lys-Arg-Ser-Gln-EDDnp
pH 7.5, 37°C
0.021
Abz-Asp-Tyr-Gln-Lys-Arg-Tyr-Gly-Gly-Phe-Leu-Lys-Arg-Phe-Ala-Glu-Ala-Leu-Gln-EDDnp
pH 7.5, 37°C
0.0046
Abz-Glu-Glu-Val-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu-Lys-Arg-Ser-Gln-EDDnp
pH 7.5, 37°C
0.00036
Abz-Leu-Leu-Ala-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Gln-EDDnp
pH 7.5, 37°C
0.014
Abz-Ser-Met-Arg-Val-Arg-Arg-His-Ser-Asp-Pro-Ala-Gln-EDDnp
pH 7.5, 37°C
0.0074
Abz-Thr-His-Arg-Ser-Lys-Arg-Ser-Ser-Ser-His-Pro-Ile-Gln-EDDnp
pH 7.5, 37°C
0.0003
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
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
0.0003
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.009
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 9, without salt
0.0028
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.004
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 9, without salt
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.07
Abz-Arg-Thr-Ser-Arg-Arg-Lys-Arg-Tyr-Ala-Glu-His-Lys-Gln-EDDnp
pH 7.5, 37°C
0.06
Abz-Asp-Met-Ser-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Ser-Leu-Lys-Arg-Ser-Gln-EDDnp
pH 7.5, 37°C
0.18
Abz-Asp-Tyr-Gln-Lys-Arg-Tyr-Gly-Gly-Phe-Leu-Lys-Arg-Phe-Ala-Glu-Ala-Leu-Gln-EDDnp
pH 7.5, 37°C
0.08
Abz-Glu-Glu-Val-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu-Lys-Arg-Ser-Gln-EDDnp
pH 7.5, 37°C
0.08
Abz-Leu-Leu-Ala-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Gln-EDDnp
pH 7.5, 37°C
0.1
Abz-Ser-Met-Arg-Val-Arg-Arg-His-Ser-Asp-Pro-Ala-Gln-EDDnp
pH 7.5, 37°C
0.2
Abz-Thr-His-Arg-Ser-Lys-Arg-Ser-Ser-Ser-His-Pro-Ile-Gln-EDDnp
pH 7.5, 37°C
7.1
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
9.2
o-aminobenzoic acid-AFRLAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
2.7
o-aminobenzoic acid-AFRVGQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
7.1
o-aminobenzoic acid-EEHAFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
9.1
o-aminobenzoic acid-EHSAFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
0.4
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 9, without salt
11.6
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
2.3
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 9, without salt
14.2
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine
-
at pH 7.5, in the presence 2 M sodium citrate
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
41
Abz-Arg-Thr-Ser-Arg-Arg-Lys-Arg-Tyr-Ala-Glu-His-Lys-Gln-EDDnp
pH 7.5, 37°C
33
Abz-Asp-Met-Ser-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Ser-Leu-Lys-Arg-Ser-Gln-EDDnp
pH 7.5, 37°C
8.6
Abz-Asp-Tyr-Gln-Lys-Arg-Tyr-Gly-Gly-Phe-Leu-Lys-Arg-Phe-Ala-Glu-Ala-Leu-Gln-EDDnp
pH 7.5, 37°C
16
Abz-Glu-Glu-Val-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu-Lys-Arg-Ser-Gln-EDDnp
pH 7.5, 37°C
228
Abz-Leu-Leu-Ala-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Gln-EDDnp
pH 7.5, 37°C
27
Abz-Thr-His-Arg-Ser-Lys-Arg-Ser-Ser-Ser-His-Pro-Ile-Gln-EDDnp
pH 7.5, 37°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000224
amyloid precursor protein Kunitz protease inhibitor domain
pH and temperature not specified in the publication
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
infected with Theiler's murine encephalomyelitis virus, gene Klk6
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
breast carcinoma cell line, enzyme is up-regulated by estrogens, progestin and slightly by androgen
brenda
quantitative real-time PCR enzyme expression analysis
brenda
quantitative real-time PCR enzyme expression analysis
brenda
73 intracranial tumor samples are screened for enzyme expression by quantitative real-time PCR analysis, overview
brenda
splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate
brenda
MCF-7 cells with low metastatic potential express KLK6 mRNA and protein levels comparable to normal human mammary epithelial cells
brenda
-
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
brenda
splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate
brenda
-
expression of hK6 is downregulated in comparison with normal salivary gland tissue
brenda
-
strong expression in stromal cells located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions
brenda
additional information
-
predominantly expressed in brain. Located not only in the activated microglia cells but also in amyloid plaque and neurofilament tangles in Alzheimer fluid
brenda
highly down-regulated at metastatic breast cancer sites
brenda
-
predominantly expressed in the central nervous system
brenda
highly expressed in the central nervous system and with elevated level in demyelinating disease
brenda
in synucleinopathies, including Parkinson disease, the levels of KLK6 inversely correlate with alpha-synuclein in cerebrospinal fluid
brenda
-
strong expression in keratinocytes located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions
brenda
-
altered morphology (spindle like cell morphology) and proliferation of keratinocytes with ectopic Klk6 expression. Klk6 expression induces keratinocyte migration and invasion
brenda
-
primary cerebellar granule neuron and NSC34 spinal cord motoneuron cell culture
brenda
-
primary cerebellar granule neuron and NSC34 spinal cord motoneuron cell culture
-
brenda
-
gene amplification is one mechanism for the overexpression of hK6 in ovarian cancer. High expression of hK6 protein in coexisting benign, borderline and invasive ovarian tumours is observed. The tumours also express high levels of kallikrein 6 mRNA
brenda
KLK6 is upregulated. In benign tumour tissue, KLK6 expression is low
brenda
splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate
brenda
weakly expressed in the epidermis of normal skin, restricted to keratinocytes of the suprabasal epidermis and hair follicles
brenda
splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate
brenda
-
Klk6 expression is elevated in the spinal cord of mice with experimental autoimmune encephalomyelitis at the peak of clinical disease
brenda
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
brenda
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
brenda
additional information
21PT cell isolated from a primary breast tumor, highly overexpresses KLK6. KLK6 expression is absent or very low in metastatic breast cancer cell lines MDA-MB-231, BT-474, MDA-MB-435, MDAMB-435P, ZR-75-1 and T47D
brenda
additional information
-
21PT cell isolated from a primary breast tumor, highly overexpresses KLK6. KLK6 expression is absent or very low in metastatic breast cancer cell lines MDA-MB-231, BT-474, MDA-MB-435, MDAMB-435P, ZR-75-1 and T47D
brenda
additional information
KLK6 is upregulated in vulva cancer cells and malignant melanomas
brenda
additional information
-
KLK6 is upregulated in vulva cancer cells and malignant melanomas
brenda
additional information
-
KRP/hK6 is present in lung small cell carcinoma and carcinoid tumour cell. Absent from lung adenocarcinoma
brenda
additional information
-
ovarian cancer ascites fluid from ovarian cancer patients during therapeutic drainage. hK6 and hK10 concentrations are positively correlated in ovarian cancer ascites fluid, majority of hK6 present in the free (uncomplexed) form
brenda
additional information
inactivated expression in metastatic breast cancer
brenda
additional information
-
inactivated expression in metastatic breast cancer
brenda
additional information
-
KLK6 is not detectable in tumor cells of primary and metastatic melanoma and is specifically absent in atypic melanocytes of dysplastic nevi
brenda
additional information
enzyme expression analysis in gastric cancer and cell lines, overview. No or poor expression in Jurkat and HS677.st cells
brenda
additional information
-
enzyme expression analysis in gastric cancer and cell lines, overview. No or poor expression in Jurkat and HS677.st cells
brenda
additional information
immunohistochemic enzyme tissue expression analysis, overview
brenda
additional information
-
immunohistochemic enzyme tissue expression analysis, overview
brenda
additional information
significantly increased enzyme expression in early invasive cancer compared with dysplastic and nondysplastic Barrett esophagus, immunohistochemic analysis, overview
brenda
additional information
-
significantly increased enzyme expression in early invasive cancer compared with dysplastic and nondysplastic Barrett esophagus, immunohistochemic analysis, overview
brenda
additional information
the enzyme is expressed more frequently in tumors of high malignancy, like the glioblastomas, and less in tumors of low malignancy, like the meningiomas. No expression in cell lines U-251-MG and D-54
brenda
additional information
-
the enzyme is expressed more frequently in tumors of high malignancy, like the glioblastomas, and less in tumors of low malignancy, like the meningiomas. No expression in cell lines U-251-MG and D-54
brenda
additional information
the level of enzyme is significantly increased in the plasma samples from the cancer cohort compared to the benign and healthy cohorts and shows a slight decrease in the postoperative plasma samples in comparison to the preoperative plasma samples, overview
brenda
additional information
-
the level of enzyme is significantly increased in the plasma samples from the cancer cohort compared to the benign and healthy cohorts and shows a slight decrease in the postoperative plasma samples in comparison to the preoperative plasma samples, overview
brenda
additional information
-
in SJL mice infected with Theiler's murine encephalomyelitis virus, enzyme expression persisted primarily in the spinal cord reaching a peak of fivefold over controls at mid-chronic stages, expression of Klk6 RNA is differentially regulated in the brain and spinal cord across the acute, subacute and more chronic phases, overview
brenda
additional information
-
quantitative PCR-based enzyme expression analysis in spinal cord injury, overview
brenda
additional information
-
quantitative PCR-based enzyme expression analysis in spinal cord injury, overview
-
brenda
additional information
-
in SJL mice infected with Theiler's murine encephalomyelitis virus, enzyme expression persisted primarily in the spinal cord reaching a peak of fivefold over controls at mid-chronic stages, expression of Klk6 RNA is differentially regulated in the brain and spinal cord across the acute, subacute and more chronic phases, overview
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
heterologous expression of pre-pro-neurosin is localized to the endoplasmic reticulum, intracellular neurosin has no protease activity
brenda
-
KLK6 localizes to caveolin-1-containing membrane fractions in the presence, but not the absence of caveolin-1
brenda
additional information
-
KRP/hK6 is cytoplasmic in brain, lung and submandibular gland and is present in the cytoplasm of squamous cell carcinoma, small cell carcinoma and carcinoid tumour. Absent from cytoplasm of tumour cells of adenocarcinoma
brenda
KLK6 expression in ovarian tumour cytosols is 57fold higher than in normal tissue and 31fold higher than in begnin and nonovarian metastatic tumours
brenda
additional information
the enzyme expression shows a granular cytoplasmic pattern of staining with luminal accentuation, immunohistochemic analysis, overview
-
brenda
additional information
-
the enzyme expression shows a granular cytoplasmic pattern of staining with luminal accentuation, immunohistochemic analysis, overview
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme is a member of the human kallikrein gene family of secreted serine proteases
malfunction
metabolism
physiological function
additional information
malfunction
-
ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line is reduced by lipopeptide inhibitors of PAR1 or PAR2, and PAR1 genetic deletion, which reduces the neurotoxic effects of the enzyme
malfunction
-
KLK6 knockout mice have thinner epidermis and decreased keratinocyte proliferation. The keratinocytes in wild type and KLK6 knockout epidermis are equally sensitive to acute anti-proliferative effect of fluocinolone acetonide. The development of proliferative resistance during chronic treatment is reduced in knockout epidermis
malfunction
KLK6-deficient primary cortical neurons have increased ability for alpha-synuclein fibril uptake
malfunction
-
ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line is reduced by lipopeptide inhibitors of PAR1 or PAR2, and PAR1 genetic deletion, which reduces the neurotoxic effects of the enzyme
-
metabolism
-
kallikrein 6 and thrombin are important regulators of neural pathophysiology and neurotoxic
metabolism
KLK6 can be a major player in the turnover of alpha-synuclein species
metabolism
-
mechanism of epidermal regeneration after glucocorticoid-induced atrophy via KLK6 activation
metabolism
-
kallikrein 6 and thrombin are important regulators of neural pathophysiology and neurotoxic
-
physiological function
KLK6 is an epigenetically regulated tumor suppressor in human breast cancer. KLK6 re-expression in nonexpressing MDA-MB-231 breast tumor cells results in significant down-regulation of vimentin which represents an established marker of epithelial transition to mesenchymal transition of tumor cells and in concomitant upregulation of calreticulin and epithelial markers cytokeratin 8 and 19. Stable expression of KLK6 reduces proliferation rates, motility, and anchorage-independent growth of MDA-MB-231 cells
physiological function
-
KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of protease-activated receptor 1. Recombinant KLK6 significantly reduces cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Immune cell survival promoting effects of KLK6 include both T and B lymphocytes and involve up regulation of the pro-survival protein B-cell lymphoma-extra large and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death
physiological function
-
KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of protease-activated receptor 1. Recombinant KLK6 significantly reduces cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Immune cell survival promoting effects of KLK6 include both T and B lymphocytes and involve up regulation of the pro-survival protein B-cell lymphoma-extra large and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death
physiological function
-
recombinant Klk6 protein significantly induces melanoma cell migration and invasion accompanied by an accelerated intracellular Ca2+ flux. KLK6-induced intracellular Ca2+ flux and tumor cell invasion critically depends on the protease-activated receptor 1
physiological function
-
involvement of Klk6 in chronic progressive demyelinating disease, regulatory activities for kallikrein 6 in the development and progression of central nervous system inflammation and demyelination, overview
physiological function
involvement of Klk6 in chronic progressive demyelinating disease, regulatory activities for kallikrein 6 in the development and progression of central nervous system inflammation and demyelination, overview
physiological function
-
kallikrein 6 is a serine protease implicated in neurodegeneration. Kallikrein 6 elicits ERK1/2 signaling in neurons by activation of protease activated receptors PAR1 and PAR2. Recombinant Klk6 triggered ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line, in a PI3K and MEK-dependent fashion. Kallikrein 6 and thrombin promote degeneration of cerebellar neurons and exacerbate glutamate neurotoxicity
physiological function
-
the enzyme activates G-protein coupled protease activated receptors. The enzyme serves as a molecular trigger of selected physiological processes involved in the development of astrogliosis and causes astrocytes to transform from an epitheliod to a stellate morphology and to secrete interleukin 6. It reduces expression of glial fibrillary acidic protein. Injury-induced elevations in enzyme level contribute to the development of astrogliosis in a protease activated receptor-dependent fashion. The enzyme stellation promoting activity is dependent on activation of the thrombin receptor, PAR1, the enzyme effects are blocked by the PAR1 specific inhibitor SCH79797. The kallikrein 6-induced astrocyte stellation is mediated by protein kinase C. Kallikrein 6 activates PAR1 in neurons and PAR1 and PAR2 in astrocytes to elicit intracellular Ca2+ flux and regulation of the mitogen activated protein kinase (MAPK) signaling pathway
physiological function
The enzyme plays a crucial role in ovarian cancer. Regulation of KLK6 activity is mediated mainly through (auto-)proteolytic activation or inactivation with most effi cient inhibition is achieved by endogenous antithrombin III
physiological function
kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition
physiological function
-
the enzyme can influence astrocyte plasticity through receptor-dependent mechanisms. Recombinant Klk6 evokes increases in intracellular Ca2+ in primary astrocyte monolayer cultures through activation of proteinase activated receptor 1 (PAR1). Klk6 promotes a condensation of astrocyte cortical actin leading to an elongated stellate shape and multicellular aggregation in a manner that is dependent on the presence of either PAR1 or PAR2. Klk6-evoked changes in astrocyte shape are accompanied by translocation of beta-catenin from the plasma membrane to the cytoplasm
physiological function
-
kallikrein 6 is a serine protease implicated in neurodegeneration. Kallikrein 6 elicits ERK1/2 signaling in neurons by activation of protease activated receptors PAR1 and PAR2. Recombinant Klk6 triggered ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line, in a PI3K and MEK-dependent fashion. Kallikrein 6 and thrombin promote degeneration of cerebellar neurons and exacerbate glutamate neurotoxicity
-
physiological function
-
involvement of Klk6 in chronic progressive demyelinating disease, regulatory activities for kallikrein 6 in the development and progression of central nervous system inflammation and demyelination, overview
-
additional information
-
Klk6 and the prototypical activator of protease activated receptor 1, PAR1, thrombin, as well as PAR1 and PAR2, are each elevated in murine experimental traumatic spinal cord injury at acute or subacute time points
additional information
significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect
additional information
-
significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect
additional information
brain-targeted neurosin accumulates throughout the CNS in neurons, astrocytes and microglia, and results in reduced accumulation of alpha-synuclein in oligodendrocytes and astrocytes with possible clearance via microglia. It also ameliorates myelin degeneration, neuropathology and behavioral deficits. The modified, brain-targeted neurosin may warrant further investigation as potential therapy for multiple system atrophy
additional information
-
brain-targeted neurosin accumulates throughout the CNS in neurons, astrocytes and microglia, and results in reduced accumulation of alpha-synuclein in oligodendrocytes and astrocytes with possible clearance via microglia. It also ameliorates myelin degeneration, neuropathology and behavioral deficits. The modified, brain-targeted neurosin may warrant further investigation as potential therapy for multiple system atrophy
additional information
-
Klk6 and the prototypical activator of protease activated receptor 1, PAR1, thrombin, as well as PAR1 and PAR2, are each elevated in murine experimental traumatic spinal cord injury at acute or subacute time points
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
31000
x * 43000, glycosylated enzyme, SDS-PAGE, x * 31000, deglycosylated enzyme, SDS-PAGE
43000
x * 43000, glycosylated enzyme, SDS-PAGE, x * 31000, deglycosylated enzyme, SDS-PAGE
additional information
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
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
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 43000, glycosylated enzyme, SDS-PAGE, x * 31000, deglycosylated enzyme, SDS-PAGE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
differential glycosylation of KLK6 is identified in ascites fluid obtained from ovarian cancer patients, suggesting the presence of unique KLK6 isoforms in biological samples
proteolytic modification
-
the enzyme is produced as a preproform. After cleavage of 16 amino acid signal peptide, the proenzyme has a single protease domain with an N-glycosylation site. the proenzyme peptide has the sequence EEQNK
proteolytic modification
the enzyme is synthesized as a preproenzyme, mainly in tissues of the central nervous system, and secreted as an inactive precursor
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of the APPIWT/KLK6 and APPI-4M/KLK6 complexes reveal the structural and mechanistic bases for the improved KLK6 binding and proteolytic resistance of APPI-4M. APPI is the amyloid precursor protein Kunitz protease inhibitor domain. APPI-4M i.e. APPI(M17L/I18F/S19F/F34V)
purified enzyme bound to inhibitor 9b, X-ray diffraction structure determination and analysis at 1.68 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S197A
additional information
additional information
deletion constructs pBLCAT6 (-80,+179) and pBLCAT6(-80,+12) do not show transactivation. KLK6 sequence downstream of +179 is important for KLK6 transcription
additional information
-
deletion constructs pBLCAT6 (-80,+179) and pBLCAT6(-80,+12) do not show transactivation. KLK6 sequence downstream of +179 is important for KLK6 transcription
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hK6 purified on immunoaffinity columns, followed by reverse-phase high performance liquid chromatography, to homogeneity
-
nickel-nitrilotriacetic acid-Sepharose column chromatography and benzamidine-Sepharose column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in a baculovirus/insect system
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
gene KLK6, genetic organization and structure of the kallikrein gene family, clustered on chromosome 19q13.3-q13.4
gene Klk6, quantitative enzyme expression analysis
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
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
-
pcDNA3.1-Klk6-Myc/His-tagged fusion protein expressed in the mouse keratinocyte cell line MCA3D
-
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
-
the enzyme is cloned into the third generation self-inactivating lentivirus vector with the CMV promoter driving expression
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
highly up-regulated in several types of cancer, where its increased activity promotes cancer invasion and metastasis
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
no change in KLK6 expression is observed upon treatment of T47D cells with trichostatin A
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
treatment of MDA-MB-231 and T47D breast tumor cell lines with 5-aza-2'-deoxycytidine results in significant induction of KLK6 expression
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
-
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
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
medicine
additional information
-
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
diagnostics
enzyme KLK6 is significantly associated with other prognostic markers in gastroesophageal junction adenocarcinoma and Barrett esophagus, including depth of invasion, indicating its potential as independent biomarker
diagnostics
human tissue kallikrein 6 as a potential marker of laryngeal cancer based on the relevant secretory/releasing protein database
diagnostics
kallikrein-related peptidases are biomarkers for prognosis, diagnosis and therapeutic intervention of cancer. KLK6 gene expression may have clinical utility as a marker of unfavorable prognosis for intracranial tumors
diagnostics
stromal cell-associated expression of kallikrein-related peptidase 6 indicates poor prognosis of ovarian cancer patients
diagnostics
the enzyme might be used as a potential biomarker and therapeutic target for gastric cancer
diagnostics
KLK6 is present in biological fluids either as free form, or bound to alpha1-antitrypsin, and the bound form performs better than total KLK6 as a biomarker of ovarian carcinoma
diagnostics
prognostic biomarker for head and neck squamous cell carcinoma patients
medicine
-
developoment of a monoclonal antibody to conform the high expression level of hK6 in ovarian tumor cells. The development of high-quality monoclonal antibodies will facilitate the evaluation of biomarkers and allow further screening tool development for early detection of avarian cancer
medicine
-
kallikrein 6 and other kallikreins have the potential as useful biomarker for salivary gland neoplasms
medicine
-
active hK6 is present in ovarian cancer ascites fluid, provides a rationale for the development of novel therapeutic strategies
medicine
-
Klk6 expression decreases E-cadherin levels at the membrane in concert with cytoplasmic and nuclear accumulation of beta-catenin. Klk6 transgene expression induces keratinocyte proliferation and migration during cutaneous wound healing
medicine
KLK6 is a biomarker for tumor diagnosis and management and a promising therapeutic target. KLK6 expression induces E-cadherin ectodomain shedding and reduces cell-cell adhesion. KLK6-induced E-cadherin ectodomain shedding requires proteolytic activity of matrix metalloproteinase and/or disintegrin and metalloproteinase
medicine
KLK6 is an unfavorable prognostic biomarker for ovarian cancer. KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction. Upregulation correlates with cancer stage
medicine
multiple co-operating mechanisms underlie the inactivation of KLK6 expression in breast cancer and provide ways for its pharmacological modulation with potential therapeutic implications
medicine
-
protease M in oligodendrocytes is closely associated with the expression of the myelin basic protein and the PLP gene. Maintenance of myelination is an important function of protease M in oligodendrocytes. The enzyme may be related to the oligodendroglial response to myelin disorders
medicine
-
tumor-associated overexpression of tissue kallikreins contributes to ovarian cancer progression. Possibily effects observed may be due to the activity of only some of the four kallikreins hK4, hK5, hK6, and hK7 under survey
medicine
the enzyme might be used as a potential biomarker and therapeutic target for gastric cancer
medicine
the enzyme might be useful as target for therapeutic intervention in case of intracranial tumors
medicine
-
Klk6 represents an important target for conditions in which pro-inflammatory responses play a critical role in disease development, including multiple sclerosis
medicine
possibility to exploit KLK6 as a novel therapeutic target for Parkinson disease and other synucleinopathies
medicine
-
protease M in oligodendrocytes is closely associated with the expression of the myelin basic protein and the PLP gene. Maintenance of myelination is an important function of protease M in oligodendrocytes. The enzyme may be related to the oligodendroglial response to myelin disorders
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Mus musculus (P15947), Homo sapiens (Q92876)
brenda
Yousef, G.M.; Diamandis, E.P.
The new human tissue kallikrein gene family: structure, function, and association to disease
Endocr. Rev.
22
184-204
2001
Homo sapiens (Q92876)
brenda
Pampalakis, G.; Kurlender, L.; Diamandis, E.P.; Sotiropoulou, G.
Cloning and characterization of novel isoforms of the human kallikrein 6 gene
Biochem. Biophys. Res. Commun.
320
54-61
2004
Homo sapiens (Q92876), Homo sapiens
brenda
Bayes, A.; Tsetsenis, T.; Ventura, S.; Vendrell, J.; Aviles, F.X.; Sotiropoulou, G.
Human kallikrein 6 activity is regulated via an autoproteolytic mechanism of activation/inactivation
Biol. Chem.
385
517-524
2004
Homo sapiens
brenda
Prezas, P.; Arlt, M.J.; Viktorov, P.; Soosaipillai, A.; Holzscheiter, L.; Schmitt, M.; Talieri, M.; Diamandis, E.P.; Krueger, A.; Magdolen, V.
Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
Biol. Chem.
387
807-811
2006
Homo sapiens
brenda
Ni, X.; Zhang, W.; Huang, K.C.; Wang, Y.; Ng, S.K.; Mok, S.C.; Berkowitz, R.S.; Ng, S.W.
Characterisation of human kallikrein 6/protease M expression in ovarian cancer
Br. J. Cancer
91
725-731
2004
Homo sapiens
brenda
Yamaguchi, N.
Neurosin or human kallikrein 6
Handbook of proteolytic enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. ) Academic Press
2
1585-1587
2004
Homo sapiens, Mus musculus, Rattus norvegicus
-
brenda
Darling, M.R.; Jackson-Boeters, L.; Daley, T.D.; Diamandis, E.P.
Human kallikrein 6 expression in salivary gland tumors
J. Histochem. Cytochem.
54
337-342
2006
Homo sapiens
brenda
Blaber, S.I.; Yoon, H.; Scarisbrick, I.A.; Juliano, M.A.; Blaber, M.
The autolytic regulation of human kallikrein-related peptidase 6
Biochemistry
46
5209-5217
2007
Homo sapiens
brenda
Pampalakis, G.; Sotiropoulou, G.
Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
Biol. Chem.
387
773-782
2006
Homo sapiens (Q92876), Homo sapiens
brenda
Shan, S.J.; Scorilas, A.; Katsaros, D.; Diamandis, E.P.
Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects
Br. J. Cancer
96
362-372
2007
Homo sapiens (Q92876), Homo sapiens
brenda
Klucky, B.; Mueller, R.; Vogt, I.; Teurich, S.; Hartenstein, B.; Breuhahn, K.; Flechtenmacher, C.; Angel, P.; Hess, J.
Kallikrein 6 induces E-cadherin shedding and promotes cell proliferation, migration, and invasion
Cancer Res.
67
8198-8206
2007
Mus musculus, Homo sapiens (Q92876), Homo sapiens
brenda
Singh, J.; Naran, A.; Misso, N.L.; Rigby, P.J.; Thompson, P.J.; Bhoola, K.D.
Expression of kallikrein-related peptidases (KRP/hK5, 7, 6, 8) in subtypes of human lung carcinoma
Int. Immunopharmacol.
8
300-306
2008
Homo sapiens
brenda
Debela, M.; Magdolen, V.; Schechter, N.; Valachova, M.; Lottspeich, F.; Craik, C.S.; Choe, Y.; Bode, W.; Goettig, P.
Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences
J. Biol. Chem.
281
25678-25688
2006
Homo sapiens (Q92876)
brenda
Angelo, P.F.; Lima, A.R.; Alves, F.M.; Blaber, S.I.; Scarisbrick, I.A.; Blaber, M.; Juliano, L.; Juliano, M.A.
Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects
J. Biol. Chem.
281
3116-3126
2006
Homo sapiens
brenda
Henkhaus, R.S.; Roy, U.K.; Cavallo-Medved, D.; Sloane, B.F.; Gerner, E.W.; Ignatenko, N.A.
Caveolin-1-mediated expression and secretion of kallikrein 6 in colon cancer cells
Neoplasia
10
140-148
2008
Homo sapiens
brenda
Bando, Y.; Ito, S.; Nagai, Y.; Terayama, R.; Kishibe, M.; Jiang, Y.P.; Mitrovic, B.; Takahashi, T.; Yoshida, S.
Implications of protease M/neurosin in myelination during experimental demyelination and remyelination
Neurosci. Lett.
405
175-180
2006
Mus musculus, Mus musculus BALB/c
brenda
Luo, L.; Soosaipillai, A.; Grass, L.; Diamandis, E.P.
Characterization of human kallikreins 6 and 10 in ascites fluid from ovarian cancer patients
Tumour Biol.
27
227-234
2006
Homo sapiens
brenda
Debela, M.; Beaufort, N.; Magdolen, V.; Schechter, N.M.; Craik, C.S.; Schmitt, M.; Bode, W.; Goettig, P.
Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
Biol. Chem.
389
623-632
2008
Homo sapiens, Homo sapiens (Q92876)
brenda
Pampalakis, G.; Arampatzidou, M.; Amoutzias, G.; Kossida, S.; Sotiropoulou, G.
Identification and analysis of mammalian KLK6 orthologue genes for prediction of physiological substrates
Comput. Biol. Chem.
32
111-121
2008
Canis lupus familiaris, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Sus scrofa, Bos taurus (A6QQ95), Bos taurus, Homo sapiens (Q92876), Homo sapiens
brenda
Oikonomopoulou, K.; Hansen, K.K.; Saifeddine, M.; Tea, I.; Blaber, M.; Blaber, S.I.; Scarisbrick, I.; Andrade-Gordon, P.; Cottrell, G.S.; Bunnett, N.W.; Diamandis, E.P.; Hollenberg, M.D.
Proteinase-activated receptors, targets for kallikrein signaling
J. Biol. Chem.
281
32095-32112
2006
Homo sapiens (Q92876)
brenda
Li, H.X.; Hwang, B.Y.; Laxmikanthan, G.; Blaber, S.I.
Blaber, M.; Golubkov, P.A.; Ren, P.; Iverson, B.L.; Georgiou, G.: Substrate specificity of human kallikreins 1 and 6 determined by phage display
Protein Sci.
17
664-672
2008
Homo sapiens (Q92876)
brenda
Pampalakis, G.; Prosnikli, E.; Agalioti, T.; Vlahou, A.; Zoumpourlis, V.; Sotiropoulou, G.
A tumor-protective role for human kallikrein-related peptidase 6 in breast cancer mediated by inhibition of epithelial-to-mesenchymal transition
Cancer Res.
69
3779-3787
2009
Homo sapiens (Q92876), Homo sapiens
brenda
Tatebe, H.; Watanabe, Y.; Kasai, T.; Mizuno, T.; Nakagawa, M.; Tanaka, M.; Tokuda, T.
Extracellular neurosin degrades alpha-synuclein in cultured cells
Neurosci. Res.
67
341-346
2010
Homo sapiens
brenda
Krenzer, S.; Peterziel, H.; Mauch, C.; Blaber, S.I.; Blaber, M.; Angel, P.; Hess, J.
Expression and function of the kallikrein-related peptidase 6 in the human melanoma microenvironment
J. Invest. Dermatol.
131
2281-2288
2011
Homo sapiens
brenda
Scarisbrick, I.A.; Epstein, B.; Cloud, B.A.; Yoon, H.; Wu, J.; Renner, D.N.; Blaber, S.I.; Blaber, M.; Vandell, A.G.; Bryson, A.L.
Functional role of kallikrein 6 in regulating immune cell survival
PLoS ONE
6
e18376
2011
Homo sapiens, Mus musculus
brenda
Scarisbrick, I.A.; Radulovic, M.; Burda, J.E.; Larson, N.; Blaber, S.I.; Giannini, C.; Blaber, M.; Vandell, A.G.
Kallikrein 6 is a novel molecular trigger of reactive astrogliosis
Biol. Chem.
393
355-367
2012
Mus musculus
brenda
Seiz, L.; Dorn, J.; Kotzsch, M.; Walch, A.; Grebenchtchikov, N.I.; Gkazepis, A.; Schmalfeldt, B.; Kiechle, M.; Bayani, J.; Diamandis, E.P.; Langer, R.; Sweep, F.C.; Schmitt, M.; Magdolen, V.
Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients
Biol. Chem.
393
391-401
2012
Homo sapiens (Q92876), Homo sapiens
brenda
Vakrakou, A.; Devetzi, M.; Papachristopoulou, G.; Malachias, A.; Scorilas, A.; Xynopoulos, D.; Talieri, M.
Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
Biol. Chem.
395
1105-1117
2014
Homo sapiens (Q92876), Homo sapiens
brenda
Liang, G.; Chen, X.; Aldous, S.; Pu, S.F.; Mehdi, S.; Powers, E.; Xia, T.; Wang, R.
Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening
Bioorg. Med. Chem. Lett.
22
2450-2455
2012
Homo sapiens (Q92876), Homo sapiens
brenda
Scarisbrick, I.A.; Yoon, H.; Panos, M.; Larson, N.; Blaber, S.I.; Blaber, M.; Rodriguez, M.
Kallikrein 6 regulates early CNS demyelination in a viral model of multiple sclerosis
Brain Pathol.
22
709-722
2012
Mus musculus, Homo sapiens (Q92876), Mus musculus SJL/J
brenda
Zhang, Y.; Zhang, Z.; Yang, L.; Xu, B.; Li, W.; Tang, P.; Zhang, Z.; Han, N.; Gao, Y.; Cheng, S.; Xiao, T.
Identification of human tissue kallikrein 6 as a potential marker of laryngeal cancer based on the relevant secretory/releasing protein database
Dis. Markers
2014
594093
2014
Homo sapiens (Q92876), Homo sapiens
brenda
Grin, A.; Samaan, S.; Tripathi, M.; Rotondo, F.; Kovacs, K.; Bassily, M.N.; Yousef, G.M.
Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma
Hum. Pathol.
46
541-548
2015
Homo sapiens (Q92876), Homo sapiens
brenda
Yoon, H.; Radulovic, M.; Wu, J.; Blaber, S.I.; Blaber, M.; Fehlings, M.G.; Scarisbrick, I.A.
Kallikrein 6 signals through PAR1 and PAR2 to promote neuron injury and exacerbate glutamate neurotoxicity
J. Neurochem.
127
283-298
2013
Mus musculus, Mus musculus C57/BL6J
brenda
Talieri, M.; Zoma, M.; Devetzi, M.; Scorilas, A.; Ardavanis, A.
Kallikrein-related peptidase 6 (KLK6) gene expression in intracranial tumors
Tumour Biol.
33
1375-1383
2012
Homo sapiens (Q92876), Homo sapiens
brenda
Kim, J.J.; Kim, J.T.; Yoon, H.R.; Kang, M.A.; Kim, J.H.; Lee, Y.H.; Kim, J.W.; Lee, S.J.; Song, E.Y.; Myung, P.K.; Lee, H.G.
Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric cancer
Tumour Biol.
33
731-738
2012
Homo sapiens (Q92876), Homo sapiens
brenda
Silva, R.N.; Oliveira, L.C.G.; Parise, C.B.; Oliveira, J.R.; Severino, B.; Corvino, A.; di Vaio, P.; Temussi, P.A.; Caliendo, G.; Santagada, V.; Juliano, L.; Juliano, M.A.
Activity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?
Biochim. Biophys. Acta
1865
558-564
2017
Homo sapiens (Q92876), Homo sapiens
brenda
Yoon, H.; Scarisbrick, I.A.
Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
Biol. Chem.
397
1277-1286
2016
Mus musculus
brenda
Yoon, H.; Radulovic, M.; Scarisbrick, I.A.
Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
Biol. Chem.
399
1041-1052
2018
Mus musculus
brenda
Santos, J.A.; Kondo, M.Y.; Freitas, R.F.; dos Santos, M.H.; Ramalho, T.C.; Assis, D.M.; Juliano, L.; Juliano, M.A.; Puzer, L.
The natural flavone fukugetin as a mixed-type inhibitor for human tissue kallikreins
Bioorg. Med. Chem. Lett.
26
1485-1489
2016
Homo sapiens
brenda
Korbakis, D.; Soosaipillai, A.; Diamandis, E.P.
Study of kallikrein-related peptidase 6 (KLK6) and its complex with alpha1-antitrypsin in biological fluids
Clin. Chem. Lab. Med.
55
1385-1396
2017
Homo sapiens (Q92876), Homo sapiens
brenda
Sananes, A.; Cohen, I.; Shahar, A.; Hockla, A.; De Vita, E.; Miller, A.K.; Radisky, E.S.; Papo, N.
A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering
J. Biol. Chem.
293
12663-12680
2018
Homo sapiens (Q92876), Homo sapiens
brenda
Schrader, C.H.; Kolb, M.; Zaoui, K.; Flechtenmacher, C.; Grabe, N.; Weber, K.J.; Hielscher, T.; Plinkert, P.K.; Hess, J.
Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients
Mol. Cancer
14
107
2015
Homo sapiens (Q92876), Homo sapiens
brenda
Spencer, B.; Valera, E.; Rockenstein, E.; Trejo-Morales, M.; Adame, A.; Masliah, E.
A brain-targeted, modified neurosin (kallikrein-6) reduces alpha-synuclein accumulation in a mouse model of multiple system atrophy
Mol. Neurodegener.
10
48
2015
Mus musculus (Q91Y82), Mus musculus
brenda
Kishibe, M.; Baida, G.; Bhalla, P.; Lavker, R.M.; Schlosser, B.; Iinuma, S.; Yoshida, S.; Dudley, J.T.; Budunova, I.
Important role of kallikrein 6 for the development of keratinocyte proliferative resistance to topical glucocorticoids
Oncotarget
7
69479-69488
2016
Mus musculus
brenda
Pampalakis, G.; Sykioti, V.; Ximerakis, M.; Stefanakou-Kalakou, I.; Melki, R.; Vekrellis, K.; Sotiropoulou, G.
KLK6 proteolysis is implicated in the turnover and uptake of extracellular alpha-synuclein species
Oncotarget
8
14502-14515
2017
Homo sapiens (Q92876)
brenda
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