Information on EC 3.4.21.B10 - neurosin and Organism(s) Homo sapiens and UniProt Accession Q92876

KLK6 activates pro-ADAMTS19

-

?

Proenkephalin + H2O

Enkephalin + ?

-

-

?

protein activator receptor + H2O

?

-

-

?

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

-

?

WAAFRFSQA + H2O

WAAFR + FSQA

-

-

?

WEAFRSSDQ + H2O

WEAFR + SSDQ

-

-

?

WEAVRSAMW + H2O

WEAVR + SAMW

-

-

?

WIGFRNAGA + H2O

WIGFR + NAGA

-

-

?

WTAFRSAYG + H2O

WTAFR + SAYG

-

-

?

WYMTRSAMG + H2O

WYMTR + SAMG

-

-

?

Abz-KLRSSQ-EDDnp + H2O

?

-

-

?

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

-

?

alpha1-Antichymotrypsin + H2O

?

-

hydrolysis of the FRET peptide derived from alpha1-antichymotrypsin

-

?

benzoyl-L-Arg-7-amido-4-methylcoumarin + H2O

benzoyl-L-Arg + 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

-

-

?

Gelatin + H2O

?

-

-

?

myelin basic protein + H2O

?

-

hydrolysis of the FRET peptide derived from human myelin basic protein

-

?

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

-

-

?

Nalpha-benzoyl-L-Arg + H2O

benzoic acid + L-Arg

-

-

?

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

-

?

Phe-Ser-Arg-7-amido-4-methylcoumarin

Phe-Ser-Arg + 7-amino-4-methylcoumarin

-

purified hK6

-

?

plasminogen + H2O

?

3 entries

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

-

?

Val-Pro-Arg-7-amido-4-methylcoumarin

Val-Pro-Arg + 7-amino-4-methylcoumarin

-

purified hK6

-

?

additional information

?

-

11 entries

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

-

?

amyloid precursor proteins + H2O

?

enzyme may play a role in development of Alzheimer's disease

647332

-

?

polypeptide + H2O

peptides

-

-

?

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

-

?

additional information

?

-

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

-

Abz-Phe-Arg-Lys-Gln-EDDnp

-

alpha2-Macroglobulin

-

-

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

-

antithrombin III

most efficient endogenous inhibitor

-

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

-

C1-inhibitor

-

691153

-

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

-

[(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

-

antipain

-

Aprotinin

-

Bovine pancreatic trypsin inhibitor

-

weak

-

Bowman-Birk inhibitor

-

weak

Ca2+

-

0.005 mM completely inhibits hK6 at pH 7.5 or 9.0

fukugetin

-

mixed-type inhibitor

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

NH4+

-

inhibits hK6 at pH 7.5 or 9.0

PMSF

-

Sodium citrate

-

inhibits the enzyme at pH 9.0

Sodium sulfate

-

inhibits the enzyme at pH 9.0

Soybean trypsin inhibitor

-

additional information

6 entries

-

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

-

EB1089

vitamin D3 analog EB1089 can restore KLK6 expression in T47D cells

estrogen

up-regulaion

progestins

up-regulaion

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

678526

caveolin-1

-

mediates both KLK6 gene expression and protein secretion

682096

-

chondroitin sulfate

-

activates hK6 in a concentration-dependent manner

dermatan sulfate

-

activates hK6 in a concentration-dependent manner

heparan sulfate

-

activates hK6 in a concentration-dependent manner

heparin

-

activates hK6 in a concentration-dependent manner

Sodium citrate

-

reveals greatest activity at pH 7.5

Sodium sulfate

-

reveals greatest activity at pH 7.5

additional information

3 entries

-

0.073

Abz-Ala-Arg-Arg-Gln-EDDnp

pH 7.5, 37°C

0.053

Abz-Ala-Arg-Lys-Gln-EDDnp

pH 7.5, 37°C

0.076

Abz-Ala-Lys-Arg-Gln-EDDnp

pH 7.5, 37°C

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

0.027

Abz-Lys-Arg-Arg-Ser-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

0.017

Abz-Lys-Leu-Arg-Arg-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

0.0012 - 0.0026

Abz-Lys-Leu-Arg-Ser-Ser-Lys-Gln-EDDnp

0.025

Abz-Lys-Lys-Arg-Ser-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

0.043

Abz-Phe-Arg-Arg-Gln-EDDnp

pH 7.5, 37°C

0.023

Abz-Phe-Arg-Lys-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

0.004

benzoyl-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

0.023

benzoyl-Ala-Lys-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

0.047

benzoyl-Ala-Phe-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

0.026

benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin

pH 7.5, 37°C

0.055

Lys-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

0.062

WAAFRFSQA

pH 7.5, 37°C

0.249

WEAFRSSDQ

pH 7.5, 37°C

0.092

WEAVRSAMW

pH 7.5, 37°C

0.182

WIGFRNAGA

pH 7.5, 37°C

0.336

WTAFRSAYG

pH 7.5, 37°C

0.069

WYMTRSAMG

pH 7.5, 37°C

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

2

Abz-Ala-Arg-Arg-Gln-EDDnp

pH 7.5, 37°C

0.04

Abz-Ala-Arg-Lys-Gln-EDDnp

pH 7.5, 37°C

1.95

Abz-Ala-Lys-Arg-Gln-EDDnp

pH 7.5, 37°C

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

4.6

Abz-Lys-Arg-Arg-Ser-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

9

Abz-Lys-Leu-Arg-Arg-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

1.5 - 2.4

Abz-Lys-Leu-Arg-Ser-Ser-Lys-Gln-EDDnp

18

Abz-Lys-Lys-Arg-Ser-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

3

Abz-Phe-Arg-Arg-Gln-EDDnp

pH 7.5, 37°C

0.09

Abz-Phe-Arg-Lys-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

8

benzoyl-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

2.5

benzoyl-Ala-Lys-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

10

benzoyl-Ala-Phe-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

6.5

benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin

pH 7.5, 37°C

9.7

Lys-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

0.9

WAAFRFSQA

pH 7.5, 37°C

1.2

WEAFRSSDQ

pH 7.5, 37°C

2

WEAVRSAMW

pH 7.5, 37°C

1.7

WIGFRNAGA

pH 7.5, 37°C

3.8

WTAFRSAYG

pH 7.5, 37°C

1.4

WYMTRSAMG

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

0.4 - 11.6

o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine

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

2.3 - 14.2

o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine

0.00083

Phe-Ser-Arg-7-amido-4-methylcoumarin

-

purified hK6

0.0003

Pro-Phe-Arg-7-amido-4-methylcoumarin

-

purified hK6

0.0013

Val-Pro-Arg-7-amido-4-methylcoumarin

-

purified hK6

27

Abz-Ala-Arg-Arg-Gln-EDDnp

pH 7.5, 37°C

0.72

Abz-Ala-Arg-Lys-Gln-EDDnp

pH 7.5, 37°C

26

Abz-Ala-Lys-Arg-Gln-EDDnp

pH 7.5, 37°C

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

170

Abz-Lys-Arg-Arg-Ser-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

529

Abz-Lys-Leu-Arg-Arg-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

570 - 1983

Abz-Lys-Leu-Arg-Ser-Ser-Lys-Gln-EDDnp

720

Abz-Lys-Lys-Arg-Ser-Ser-Lys-Gln-EDDnp

pH 7.5, 37°C

70

Abz-Phe-Arg-Arg-Gln-EDDnp

pH 7.5, 37°C

3.8

Abz-Phe-Arg-Lys-Gln-EDDnp

pH 7.5, 37°C

7

Abz-Ser-Met-Arg-Val-Arg-Arg-His-Ser-Asp-Pro-Ala-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

2000

benzoyl-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

107

benzoyl-Ala-Lys-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

210

benzoyl-Ala-Phe-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

250

benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin

pH 7.5, 37°C

190

Lys-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin

pH 7.5, 37°C

0.031

Abz-Phe-Arg-Lys-Gln-EDDnp

pH 7.5, 37°C

0.00000224

amyloid precursor protein Kunitz protease inhibitor domain

pH and temperature not specified in the publication

-

0.00000016

APPI-4M

pH and temperature not specified in the publication

-

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

0.0135

fukugetin

Homo sapiens

-

at pH 7.5 and 37°C

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

-

low enzyme expression

-

-

-

-

breast carcinoma cell

breast carcinoma cell line, enzyme is up-regulated by estrogens, progestin and slightly by androgen

-

-

central nervous system

in synucleinopathies, including Parkinson disease, the levels of KLK6 inversely correlate with alpha-synuclein in cerebrospinal fluid

choroid plexus papilloma cell

-

colonic adenocarcinoma cell

gastroesophageal junction adenocarcinoma cell

quantitative real-time PCR enzyme expression analysis

quantitative real-time PCR enzyme expression analysis

grade II

Barrett esophagus with and without dysplasia

-

early stage

-

haemaglioblastoma cell

-

barely expresses KLK6

-

intracranial tumor cell

73 intracranial tumor samples are screened for enzyme expression by quantitative real-time PCR analysis, overview

-

laryngeal cancer cell

non-Hodgkin lymphoma cell

primary tissue culture

-

-

splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate

MCF-7 cells with low metastatic potential express KLK6 mRNA and protein levels comparable to normal human mammary epithelial cells

-

-

-

-

-

-

-

732960

oligodendroglioma cell

-

-

ovarian carcinoma cell

squamous cell carcinoma cell

up-regulated in primary tumors

-

-

splice variant 3 is preferentially expressed in spinal cord, mammary, and salivary glands and to lesser extent in protstate

-

-

-

very low enzyme expression

-

-

-

-

-

-

KLK6 is upregulated

-

-

high expression level

-

central nervous system

-

predominantly expressed in the central nervous system

cerebrospinal fluid

lung squamous cell carcinoma cell

-

present as the proenzyme

-

-

-

-

strong expression in keratinocytes located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions

-

-

-

neurofibrillary tangle

-

-

-

salivary gland tumor cell

-

expression of hK6 is downregulated in comparison with normal salivary gland tissue

665904

stromal cell

-

strong expression in stromal cells located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions

717956

additional information

KLK6 expression in ovarian tumour cytosols is 57fold higher than in normal tissue and 31fold higher than in begnin and nonovarian metastatic tumours

-

endoplasmic reticulum

-

heterologous expression of pre-pro-neurosin is localized to the endoplasmic reticulum, intracellular neurosin has no protease activity

-

extracellular neurosin has protease activity

-

nucleus

-

KRP/hK6 is nuclear in glial cells of the brain

-

KLK6 localizes to caveolin-1-containing membrane fractions in the presence, but not the absence of caveolin-1

5886

682096

additional information

evolution

the enzyme is a member of the human kallikrein gene family of secreted serine proteases

731898

malfunction

KLK6-deficient primary cortical neurons have increased ability for alpha-synuclein fibril uptake

metabolism

KLK6 can be a major player in the turnover of alpha-synuclein species

physiological function

4 entries

physiological function

additional information

Q92876 pBLAST

KLK6_HUMAN

244

0

26856

Swiss-Prot

Show Sequence

-

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

24000

-

calculated from amino acid sequence

25866

-

x * 25866, SDS-PAGE

30000

-

purified hK6, Western blot analysis

32000

-

SDS-PAGE

additional information

?

x * 43000, glycosylated enzyme, SDS-PAGE, x * 31000, deglycosylated enzyme, SDS-PAGE

?

glycoprotein

proteolytic modification

glycoprotein

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

-

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

-

S197A

inactive mutant enzyme

R80Q

-

mutation stabilizes the activity of the mature enzyme

S197A

-

mutation results in complete loss of hK6 proteolytic activity

additional information

4 entries

by metal affinity resin

679036

nickel-nitrilotriacetic acid-Sepharose column chromatography and benzamidine-Sepharose column chromatography

-

-

by sequential affinity chromatography utilizing Ni-NTA

-

hK6 purified on immunoaffinity columns, followed by reverse-phase high performance liquid chromatography, to homogeneity

-

recombinant

-

-

expressed in Escherichia coli M15(pREP4) cells

680680

expresssion in Pichia pastoris

gene encodes for multiple transcript variants

691921

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

732962

gene KLK6, genetic organization and structure of the kallikrein gene family, clustered on chromosome 19q13.3-q13.4

647332

gene Klk6, quantitative enzyme expression analysis

731563

gene KLK6, quantitative real-time PCR expression analysis

732960

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

678526

pcDNA3.1-KLK6-Myc/His vector expressed in HEK-293 cells

679036

quantitative real-time PCR expression analysis

731404

expressed from a baculovirus/insect cell line system

-

expressed in a baculovirus/insect system

-

718279

expressed in HEK-293T 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

-

664273

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 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)

-

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

731563

no change in KLK6 expression is observed upon treatment of T47D cells with trichostatin A

707981

stepwise expression increase from metaplasia to dysplasia and invasive tumors, significantly increased enzyme expression in early invasive cancer, overview

731898

the enzyme is up-regulated in ovarian cancer

treatment of MDA-MB-231 and T47D breast tumor cell lines with 5-aza-2'-deoxycytidine results in significant induction of KLK6 expression

-

diagnostics

medicine

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

395498

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

Homo sapiens (Q92876), Mus musculus (P15947)

12520024

647332

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)

11294823

663841

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

15207701

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

15255184

664273

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

16800744

664465

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

15305183

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

-

665904

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

16286664

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

17417874

678526

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

16800739

678956

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

17242704

679036

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

Homo sapiens (Q92876), Homo sapiens, Mus musculus

17804733

680177

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

18182244

680680

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)

16740631

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

16321973

682096

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

18283336

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

16864975

691153

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)

18627343

691921

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

Bos taurus (A6QQ95), Bos taurus, Canis lupus familiaris, Homo sapiens (Q92876), Homo sapiens, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Sus scrofa

18243805

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)

16885167

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)

18359858

707981

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

19383923

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

20403393

717956

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

21753781

718279

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

21464892

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

22505521

731404

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

25153391

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

22386244

731563

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

Homo sapiens (Q92876), Mus musculus, Mus musculus SJL/J

22335454

731704

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

24669031

731898

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

25649006

732960

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

22477710

732962

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

22373580

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

28254587

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

26848109

753300

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

28672746

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

29934309

754702

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

25990935