3.4.21.B10: neurosin
This is an abbreviated version!
For detailed information about neurosin, go to the full flat file.
Word Map on EC 3.4.21.B10
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3.4.21.B10
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kallikreins
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trypsin-like
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medicine
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klk8
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par1
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diagnostics
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immunofluorometric
- 3.4.21.B10
- kallikreins
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trypsin-like
- medicine
- klk8
- par1
- diagnostics
-
immunofluorometric
Reaction
proteolytic cleavage of polypeptides =
Synonyms
GK, hK6, KAL-B, kallikrein 6, kallikrein-6, kallikrein-related peptidase, kallikrein-related peptidase 6, KLK6, KRP/hK6, myelencephalonspecific protease, neurosin, protease M, S01.236, serine protease 18, serine protease 9, SP59, tissue kallikrein 6, zyme
ECTree
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Substrates Products
Substrates Products on EC 3.4.21.B10 - neurosin
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REACTION DIAGRAM
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
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-
-
?
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
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-
-
?
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
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-
?
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
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-
?
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
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-
?
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
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-
?
Abz-Lys-Arg-Arg-Ser-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Arg-Arg + Ser-Ser-Lys-Gln-EDDnp
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-
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?
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
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-
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?
Abz-Lys-Leu-Arg-Ser-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Leu-Arg + Ser-Ser-Lys-Gln-EDDnp
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-
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?
Abz-Lys-Lys-Arg-Ser-Ser-Lys-Gln-EDDnp + H2O
Abz-Lys-Lys-Arg + Ser-Ser-Lys-Gln-EDDnp
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-
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?
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
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-
-
?
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
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-
?
alpha1-Antichymotrypsin + H2O
?
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hydrolysis of the FRET peptide derived from alpha1-antichymotrypsin
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-
?
benzoyl-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
benzoyl-Ala-Arg + Arg-7-amido-4-carbamoylmethylcoumarin
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-
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?
benzoyl-Ala-Lys-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
benzoyl-Ala-Lys + Arg-7-amido-4-carbamoylmethylcoumarin
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-
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?
benzoyl-Ala-Phe-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
benzoyl-Ala-Phe + Arg-7-amido-4-carbamoylmethylcoumarin
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?
benzoyl-L-Arg-7-amido-4-methylcoumarin + H2O
benzoyl-L-Arg + 7-amino-4-methylcoumarin
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?
benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
benzoyl-Arg + Arg-7-amido-4-methylcoumarin
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?
benzyloxycarbonyl-FR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-FR + 7-amino-4-methylcoumarin
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?
benzyloxycarbonyl-L-Gln-L-Ala-L-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-Gln-L-Ala-L-Arg + 7-amino-4-methylcoumarin
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?
benzyloxycarbonyl-LR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-LR + 7-amino-4-methylcoumarin
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?
Lys-Ala-Arg-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
Lys-Ala-Arg + Arg-7-amido-4-carbamoylmethylcoumarin
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?
N-alpha-tert-butyloxycarbonyl-Gln-Ala-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Gln-Ala-Arg + 7-amino-4-methylcoumarin
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?
N-alpha-tert-butyloxycarbonyl-Phe-Ser-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Phe-Ser-Arg + 7-amino-4-methylcoumarin
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?
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg-7-amido-4-methylcoumarin + H2O
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg + 7-amino-4-methylcoumarin
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?
o-aminobenzoic acid-AFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-AFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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best synthetic substrate
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?
o-aminobenzoic acid-AFRLAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-AFRVGQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-EEHAFRFSQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-EELAFKFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-EEQNKLVH-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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low rates of hydrolysis of the pro-peptide substrate by KLK6
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?
o-aminobenzoic acid-EHSAFRFAQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-KLRSSKQ-N-[2,4-dinitrophenyl]ethylenediamine + H2O
?
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?
o-aminobenzoic acid-NLRQRESS-[2,4-dinitrophenyl]ethylenediamine + H2O
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autolysis loop substrate is hydrolyzed with 2-3 order of magnitude greater efficiency than the pro-peptide substrate
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?
peptide + H2O
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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
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?
Phe-Ser-Arg-7-amido-4-methylcoumarin
Phe-Ser-Arg + 7-amino-4-methylcoumarin
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purified hK6
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?
precursor of the Abeta amyloid peptid + H2O
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hydrolysis of the FRET peptide derived from human precursor of the Abeta amyloid peptide
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?
pro-KLK6 + H2O
?
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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
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?
Pro-Phe-Arg-7-amido-4-methylcoumarin
Pro-Phe-Arg + 7-amino-4-methylcoumarin
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purified hK6
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?
proteinase-activated receptor 1 + H2O
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main cleavage site: NATLDPR-/-SFLLRNPNDKYE
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?
proteinase-activated receptor 2 + H2O
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main cleavage site: GTNRSSKGR-/-SLIGKVDGTSHVTGKGVT
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?
proteinase-activated receptor 4 + H2O
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main cleavage site: GDDSTPSILPAPR-/-GYPGOV
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?
Val-Pro-Arg-7-amido-4-methylcoumarin
Val-Pro-Arg + 7-amino-4-methylcoumarin
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purified hK6
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?
?
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neurosin may degrade alpha-synuclein, a major component of the Lewy bodies commonly observed in dopaminergic neurons of patients with sporadic Parkinsons disease
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?
alpha-synuclein + H2O
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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
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?
alpha-synuclein + H2O
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the enzyme cleaves human monomeric and mouse fibrilar alpha-synuclein, leading to the appearance of proteolytic peptide fragments below 15 kDa
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?
amyloid precursor proteins + H2O
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enzyme may play a role in development of Alzheimer's disease
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?
myelin basic protein + H2O
?
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hydrolysis of the FRET peptide derived from human myelin basic protein
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?
myelin basic protein + H2O
?
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close relationship between protease M and myelin proteins
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?
myelin basic protein + H2O
?
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close relationship between protease M and myelin proteins
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?
plasminogen + H2O
?
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the enzyme is regulated by an autoactivation/autoinactivation mechanism. Mature hK67 displays a trypsin-like activity against human plasminogen, the putative physiological substrate
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?
plasminogen + H2O
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hydrolysis of the FRET peptide derived from plasminogen
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?
mature protease activated receptor 1 + ?
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?
proform protease activated receptor 1 + H2O
mature protease activated receptor 1 + ?
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?
mature protease activated receptor 2 + ?
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?
proform protease activated receptor 2 + H2O
mature protease activated receptor 2 + ?
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?
?
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enzyme is involved in breast and ovarian cancer
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?
additional information
?
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hK6 does not hydrolyze the Nalpha-tosyl-L-Arg methyl ester
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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strong preference for P1-Arg over Lys, which is accepted nearly equally as well as Ala, Met, and Nle
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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the enzyme activates G-protein coupled protease activated receptors
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?