Any feedback?
No. of entries
Information on EC 3.4.21.B12 - prostase
for references in articles please use BRENDA:EC3.4.21.B12
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Old data from external sources may still be available.
Please check here for current data: EC unknown
Please check here for current data: EC unknown
preliminary BRENDA-supplied EC number
EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.21 Serine endopeptidases
3.4.21.B12 prostase
The enzyme appears in viruses and cellular organisms
- 3.4.21.B12
- klk4
- kallikreins
- amelogenins
-
amelogenesis
- ameloblastin
- enamelysin
- incisor
- imperfecta
-
maturation-stage
-
amelx
-
amelotin
- medicine
-
secretory-stage
-
hypomineralized
- masp-1
-
hypomaturation
-
crystallite
-
metalloproteinase-20
- analysis
- diagnostics
showSynonyms
kallikrein 4, serine protease 1, kallikrein-related peptidase 4, emsp1, kallikrein-4, prss17, prostase, kallikrein-related peptidase-4, klk-l1, klk-4 proteinase, more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EMSP1
HK4
K4
kallikrein 4
kallikrein-4
kallikrein-related peptidase 4
kallikrein-related peptidase-4
KLK-L1
KLK4
PRSS17
S01.251
-
-
-
-
serine protease 1
serine protease 17
additional information
HK4
displays a trypsin-like specificity with strong preference for P1-Arg
kallikrein 4
-
-
-
-
additional information
PRSS17 is not a member of the kallikrein gene family of serine proteases but has originated prior to the divergence of the kallikrein and trypsin families of proteases
additional information
Q9JIS2
PRSS17 is not a member of the kallikrein gene family of serine proteases but has originated prior to the divergence of the kallikrein and trypsin families of proteases
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolysis of polypeptides
substrate binding pocket contains an Asp residue
proteolysis of polypeptides
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
226408-87-3
-
9001-01-8
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(Abz)-SKGR-SLIGK(N-[2,4-dintrophenyl]ethylenediamine)-Asp-OH
?
-
Substrates: fluorescence quenched peptide spanning the PAR-2 activation site, is rapidly cleaved by KLK4
Products: -
Products: -
?
32 kDa enamelin + H2O
?
-
Substrates: five cleavage sites on the C-terminal sides of R180, Y205, H206, M219 and R262. Kallikrein 4 digestion of the 32 kDa enamelin generates nine major cleavage products. 12 h of digestion with KLK4, all of the 32 kDa enamelin has been cleaved. Some cleavage products persist after 48 h of digestion
Products: -
Products: -
?
52 kDa prostatic acid phosphatase + H2O
33 kDa prostatic acid phosphatase + 19 kDa fragment
acetyl-FVQR-4-nitroanilide + H2O
acetyl-FVQR + 4-nitroaniline
Substrates: -
Products: -
Products: -
?
benzoyl-L-Ile-L-Glu-Gly-L-Arg-4-nitroanilide + H2O
benzoyl-L-Ile-L-Glu-Gly-L-Arg + 4-nitroaniline
benzyloxycarbonyl-FR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-FR + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-LR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-LR + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-VPR-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-VPR + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
D-Val-Leu-Arg-7-amido-4-trifluoromethyl coumarin + H2O
D-Val-Leu-Arg + 7-amino-4-trifluoromethyl coumarin
Substrates: -
Products: -
Products: -
?
EKK-7-amido-4-methylcoumarin + H2O
EKK + 7-amino-4-methylcoumarin
-
Substrates: 9% of the activity with VPR-7-amido-4-methylcoumarin
Products: -
Products: -
?
GPR-7-amido-4-methylcoumarin + H2O
GPR + 7-amino-4-methylcoumarin
-
Substrates: 20% of the activity with VPR-7-amido-4-methylcoumarin
Products: -
Products: -
?
human ephrin-B2 + H2O
?
Substrates: low activity with recombinant human enzyme and human substrate
Products: -
Products: -
?
murine ephrin-B2 + H2O
?
Substrates: the substrate harbors N-glycosylation sites its extracellular domain sequence, R27-R178, good activity with recombinant human enzyme and murine substrate, the primary enzyme cleavage site in murine ephrin-B2 is verified as located between extracellular domain residues Arg178 and N179
Products: cleavage fragments, overview
Products: cleavage fragments, overview
?
pro-brain-derived neurotrophic factor + H2O
brain-derived neurotrophic factor + propeptide
Substrates: -
Products: -
Products: -
?
pro-urokinase-type plasminogen activator + H2O
activated urokinase-type plasminogen activator
proform of KLK3 + H2O
?
Substrates: Ile-Leu-Ser-Arg-/-Ile-Val activation site
Products: -
Products: -
?
protease-activated receptor-1 + H2O
?
-
Substrates: KLK4 cleaves protease-activated receptor-1 at the activation site on intact cell surface
Products: -
Products: -
?
QAR-7-amido-4-methylcoumarin + H2O
QAR + 7-amino-4-methylcoumarin
-
Substrates: 38% of the activity with VPR-7-amido-4-methylcoumarin
Products: -
Products: -
?
tosyl-Gly-Pro-Arg-7-amido-4-methylcoumarin + H2O
tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
urokinase-type plasminogen activator receptor + H2
?
-
Substrates: cleavage occurs in D1-D2 linker sequence and, to a lesser extent, in D3 juxtamembrane domain
Products: -
Products: -
?
urokinase-type plasminogen activator receptor + H2O
?
Substrates: cleaves after Thr-Tyr-Ser-Arg as well as in the sequence Val-Gln-Tyr-Arg-/-Ser-Gly
Products: -
Products: -
?
VLK-7-amido-4-methylcoumarin + H2O
VLK + 7-amino-4-methylcoumarin
-
Substrates: 60% of the activity with VPR-7-amido-4-methylcoumarin
Products: -
Products: -
?
VPR-7-amido-4-methylcoumarin + H2O
VPR + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
52 kDa prostatic acid phosphatase + H2O
33 kDa prostatic acid phosphatase + 19 kDa fragment
-
Substrates: recombinant self-activated, chimeric enzyme
Products: products contain 256 and 73 amino acid residues, respectively
Products: products contain 256 and 73 amino acid residues, respectively
?
52 kDa prostatic acid phosphatase + H2O
33 kDa prostatic acid phosphatase + 19 kDa fragment
-
Substrates: primary cleavage site is the Arg73-Ser74 bond
Products: products contain 256 and 73 amino acid residues, respectively
Products: products contain 256 and 73 amino acid residues, respectively
?
52 kDa prostatic acid phosphatase + H2O
33 kDa prostatic acid phosphatase + 19 kDa fragment
-
Substrates: inactivation of substrate
Products: products contain 256 and 73 amino acid residues, respectively
Products: products contain 256 and 73 amino acid residues, respectively
?
52 kDa prostatic acid phosphatase + H2O
33 kDa prostatic acid phosphatase + 19 kDa fragment
-
Substrates: enzyme may be involved in the physiological clearance of prostatic acid phosphatase
Products: -
Products: -
?
amelogenin + H2O
?
Substrates: the enzyme plays a pivotal role during dental enamel formation by degrading the major enamel protein, amelogenin, prior to the final steps of enamel hardening. KLK4 self-destructs once amelogenin is degraded. It progressively loses activity, becomes aggregated, and autofragmented when incubated without substrate in both the presence and absence of reducer. However, with non-ionic detergent present as proxy substrate, KLK4 remains active and intact throughout
Products: -
Products: -
?
amelogenin + H2O
amelogenin fragments
Substrates: recombinant substrate from pig expressed in Escherichia coli strain XL-1 blue as His-tagged protein
Products: product identification by N-terminal sequencing and mass spectrometry
Products: product identification by N-terminal sequencing and mass spectrometry
?
amelogenin + H2O
amelogenin fragments
Substrates: 20 kDa substrate
Products: -
Products: -
?
amelogenin + H2O
amelogenin fragments
Substrates: 20 kDa substrate
Products: -
Products: -
?
benzoyl-L-Ile-L-Glu-Gly-L-Arg-4-nitroanilide + H2O
benzoyl-L-Ile-L-Glu-Gly-L-Arg + 4-nitroaniline
-
Substrates: recombinant self-activated, chimeric enzyme
Products: -
Products: -
?
benzoyl-L-Ile-L-Glu-Gly-L-Arg-4-nitroanilide + H2O
benzoyl-L-Ile-L-Glu-Gly-L-Arg + 4-nitroaniline
-
Substrates: fluorogenic substrate, i.e. S-2222
Products: -
Products: -
?
D-Pro-L-Phe-L-Arg-4-nitroanilide + H2O
D-Pro-L-Phe-L-Arg + 4-nitroaniline
-
Substrates: recombinant self-activated, chimeric enzyme
Products: -
Products: -
?
D-Pro-L-Phe-L-Arg-4-nitroanilide + H2O
D-Pro-L-Phe-L-Arg + 4-nitroaniline
-
Substrates: fluorogenic substrate, i.e. S-2302
Products: -
Products: -
?
D-Val-L-Leu-L-Lys-4-nitroanilide + H2O
D-Val-L-Leu-L-Lys + 4-nitroaniline
-
Substrates: recombinant self-activated, chimeric enzyme
Products: -
Products: -
?
D-Val-L-Leu-L-Lys-4-nitroanilide + H2O
D-Val-L-Leu-L-Lys + 4-nitroaniline
-
Substrates: fluorogenic substrate, i.e. S-2251
Products: -
Products: -
?
D-Val-Leu-Arg-4-nitroanilide + H2O
D-Val-Leu-Arg + 4-nitroaniline
-
Substrates: recombinant self-activated, chimeric enzyme
Products: -
Products: -
?
D-Val-Leu-Arg-4-nitroanilide + H2O
D-Val-Leu-Arg + 4-nitroaniline
-
Substrates: fluorogenic substrate, i.e. S-2266
Products: -
Products: -
?
matrix metalloproteinase-1 + H2O
?
Substrates: the enzyme activates matrix metalloproteinase-1, a protease that promotes prostate tumor growth and metastasis. Matrix metalloproteinase-1 is produced in the tumor compartment of prostate cancer bone metastases, highlighting its accessibility to KLK4 at this site
Products: -
Products: -
?
plasma hepatocyte growth factor activator zymogen + H2O
mature HGF activator + ?
Substrates: activation, hepatocyte growth factor is mainly secreted from fibroblasts as an inactive single-chain precursor, which lacks biological activity
Products: -
Products: -
?
plasma hepatocyte growth factor activator zymogen + H2O
mature HGF activator + ?
Substrates: conversion to an active two-chain form
Products: -
Products: -
?
polypeptide + H2O
peptides
Substrates: enzyme is involved in degradation of extracellular matrix and activation of prostate specific antigen PSA and other proteases
Products: -
Products: -
?
polypeptide + H2O
peptides
Substrates: enzyme is regulated by steroid hormones
Products: -
Products: -
?
polypeptide + H2O
peptides
Substrates: enzyme may be involved in the pathogenesis and/or progression of prostate, breast, and possibly other malgnancies
Products: -
Products: -
?
polypeptide + H2O
peptides
-
Substrates: enzyme plays a role in the physiologic processing of seminal plasma proteins , e.g. pro-PSA, as well as in the pathogenesis of prostate cancer through the activation of pro-PSA
Products: -
Products: -
?
pro-prostate-specific antigen + H2O
activated prostate-specific antigen
-
Substrates: activation of substrate
Products: -
Products: -
?
pro-prostate-specific antigen + H2O
activated prostate-specific antigen
-
Substrates: recombinant self-activated, chimeric enzyme
Products: -
Products: -
?
pro-prostate-specific antigen + H2O
activated prostate-specific antigen
-
Substrates: i.e. PSA
Products: -
Products: -
?
pro-prostate-specific antigen + H2O
activated prostate-specific antigen
-
Substrates: activation of PSA
Products: -
Products: -
?
pro-urokinase-type plasminogen activator + H2O
activated urokinase-type plasminogen activator
-
Substrates: activation of substrate
Products: -
Products: -
?
pro-urokinase-type plasminogen activator + H2O
activated urokinase-type plasminogen activator
-
Substrates: recombinant self-activated, chimeric enzyme
Products: -
Products: -
?
pro-urokinase-type plasminogen activator + H2O
activated urokinase-type plasminogen activator
-
Substrates: i.e. pro-uPA
Products: -
Products: -
?
thrombospondin-1 + H2O
?
Substrates: the enzyme liberates an N-terminal product, with purported angiogenic activity, from thrombospondin-1. It cleaves thrombospondin-1 in osteoblast-derived matrix
Products: -
Products: -
?
urokinase-type plasminogen activator + H2O
?
Substrates: cleaves after Pro-Arg-Phe-Lys
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with serum albumin from human seminal plasma
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme has a trypsin-type substrate specificty
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with pyroglu-Gly-Arg-4-nitroanilide, i.e. S-2444, and with 3-carbomethoxypropionyl-L-Arg-L-Pro-L-Tyr-4-nitroanilide, i.e. S-2586
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme is regulated by steroid hormones, contains androgen response elements in the proximal promotor region
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme modulates the tumor-associated urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system activity by either activating the pro-enzyme form of urokinase-type plasminogen activator or cleaving the cell surface-associated urokinase-type plasminogen activator receptor
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is involved in tissue remodeling and cancer metastasis
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme cleaves more efficiently after Arg compared to Lys at the P1 position and exhibits modest specificity for amino acids at P2 and P3 positions
Products: -
Products: -
?
additional information
?
-
Substrates: clearly prefers P1-Arg over Lys and Tyr
Products: -
Products: -
?
additional information
?
-
-
Substrates: KLK4 initiates phosphorylation of ERK1/2 via PAR-2
Products: -
Products: -
?
additional information
?
-
Substrates: kallikrein-4 is a serine protease expressed during enamel maturation, and proteolytic processing of the enamel matrix by KLK4 is critical for proper enamel formation. In vitro dipeptidyl peptidase I activates pro-KLK4 to cleave a fluorogenic peptide containing a KLK4 cleavage site
Products: -
Products: -
?
additional information
?
-
Substrates: preference for Arg over Lys at position P1. KLK4 prefers as P2 residue the medium-sized polar Gln over the more hydrophobic Val, Leu, Thr, and Pro, whereas large aromatic and basic side chains are not accepted. Marked specificity for medium-sized to large hydrophobic P4 residues. Activation cleavage site: SCSQ-IING
Products: -
Products: -
?
additional information
?
-
Substrates: two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme performs proteolytic autoactivation
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme performs proteolytic autoactivation
Products: -
Products: -
?
additional information
?
-
Substrates: position of predicted enzyme cleavage sites within the sequence and the folded protein, structure, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: position of predicted enzyme cleavage sites within the sequence and the folded protein, structure, overview
Products: -
Products: -
?
additional information
?
-
Substrates: recombinant zymogen can be activated by thermolysin
Products: -
Products: -
?
additional information
?
-
-
Substrates: recombinant zymogen can be activated by thermolysin
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme participates in the degradation of enamel proteins in vivo
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme participates in the degradation of enamel proteins in vivo
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
52 kDa prostatic acid phosphatase + H2O
33 kDa prostatic acid phosphatase + 19 kDa fragment
-
Substrates: enzyme may be involved in the physiological clearance of prostatic acid phosphatase
Products: -
Products: -
?
amelogenin + H2O
?
Substrates: the enzyme plays a pivotal role during dental enamel formation by degrading the major enamel protein, amelogenin, prior to the final steps of enamel hardening. KLK4 self-destructs once amelogenin is degraded. It progressively loses activity, becomes aggregated, and autofragmented when incubated without substrate in both the presence and absence of reducer. However, with non-ionic detergent present as proxy substrate, KLK4 remains active and intact throughout
Products: -
Products: -
?
matrix metalloproteinase-1 + H2O
?
Substrates: the enzyme activates matrix metalloproteinase-1, a protease that promotes prostate tumor growth and metastasis. Matrix metalloproteinase-1 is produced in the tumor compartment of prostate cancer bone metastases, highlighting its accessibility to KLK4 at this site
Products: -
Products: -
?
plasma hepatocyte growth factor activator zymogen + H2O
mature HGF activator + ?
Substrates: activation, hepatocyte growth factor is mainly secreted from fibroblasts as an inactive single-chain precursor, which lacks biological activity
Products: -
Products: -
?
protease-activated receptor-1 + H2O
?
-
Substrates: KLK4 cleaves protease-activated receptor-1 at the activation site on intact cell surface
Products: -
Products: -
?
thrombospondin-1 + H2O
?
Substrates: the enzyme liberates an N-terminal product, with purported angiogenic activity, from thrombospondin-1. It cleaves thrombospondin-1 in osteoblast-derived matrix
Products: -
Products: -
?
polypeptide + H2O
peptides
Substrates: enzyme is involved in degradation of extracellular matrix and activation of prostate specific antigen PSA and other proteases
Products: -
Products: -
?
polypeptide + H2O
peptides
Substrates: enzyme is regulated by steroid hormones
Products: -
Products: -
?
polypeptide + H2O
peptides
Substrates: enzyme may be involved in the pathogenesis and/or progression of prostate, breast, and possibly other malgnancies
Products: -
Products: -
?
polypeptide + H2O
peptides
-
Substrates: enzyme plays a role in the physiologic processing of seminal plasma proteins , e.g. pro-PSA, as well as in the pathogenesis of prostate cancer through the activation of pro-PSA
Products: -
Products: -
?
pro-prostate-specific antigen + H2O
activated prostate-specific antigen
-
Substrates: i.e. PSA
Products: -
Products: -
?
pro-prostate-specific antigen + H2O
activated prostate-specific antigen
-
Substrates: activation of PSA
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme is regulated by steroid hormones, contains androgen response elements in the proximal promotor region
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme modulates the tumor-associated urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system activity by either activating the pro-enzyme form of urokinase-type plasminogen activator or cleaving the cell surface-associated urokinase-type plasminogen activator receptor
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is involved in tissue remodeling and cancer metastasis
Products: -
Products: -
?
additional information
?
-
Substrates: kallikrein-4 is a serine protease expressed during enamel maturation, and proteolytic processing of the enamel matrix by KLK4 is critical for proper enamel formation. In vitro dipeptidyl peptidase I activates pro-KLK4 to cleave a fluorogenic peptide containing a KLK4 cleavage site
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme performs proteolytic autoactivation
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme performs proteolytic autoactivation
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme participates in the degradation of enamel proteins in vivo
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme participates in the degradation of enamel proteins in vivo
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
MCoTI-II
a 34-amino acid cyclic peptide found in the seeds of Momordica cochinchinensis. By grafting a preferred KLK4 cleavage sequence into MCoTI-II, a highly potent KLK4 inhibitor is produced that displays 100000fold selectivity over related kallikreins and the ability to penetrate cells. Additionally, by substituting positively charged noncontact residues in this compound, a potent and selective KLK4 inhibitor is produced that does not penetrate cells. The inhibitors are shown to be nontoxic to human cells and stable in human serum. These KLK4 inhibitors provide useful chemical tools to further define the role(s) of both intracellular and extracellular KLK4 in prostate cancer cell lines and disease models
-
siRNA
-
mediates knockdown of endogenous KLK4 in LNCaP prostate cancer cells whereby inhibiting their proliferation
-
Zn2+
-
enzyme activity is high at zinc concentrations below 0.001 mM and decreases to about 30% at 0.1 mM. Zinc affects the K4 active site via the salt-bridge formed between the N terminus and Asp194 required for a functional active site
Aprotinin
-
complex formation with the self-activated recombinant, chimeric enzyme
additional information
inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines
-
additional information
-
inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
no activation of recombinant zymogen by native KLK4 enzyme in vitro
-
additional information
-
no activation of recombinant zymogen by native KLK4 enzyme in vitro
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Kallikrein 4 is expressed in malignant mesothelioma--further evidence for the histogenetic link between mesothelial and epithelial cells.
Adenocarcinoma
Kallikrein-related peptidase 4 (KLK4) mRNA predicts short-term relapse in colorectal adenocarcinoma patients.
Amelogenesis Imperfecta
Human enamel phenotype associated with amelogenesis imperfecta and a kallikrein-4 (g.2142G>A) proteinase mutation.
Amelogenesis Imperfecta
Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta.
Breast Neoplasms
Specific increase of human kallikrein 4 mRNA and protein levels in breast cancer stromal cells.
Carcinogenesis
Kallikrein-related peptidase signaling in colon carcinoma cells: Targeting proteinase-activated receptors (PARs).
Carcinogenesis
MiR-378a-5p inhibits angiogenesis of oral squamous cell carcinoma by targeting KLK4.
Carcinoma
Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions.
Carcinoma
Kallikrein-related peptidase 4 contributes to the tumor metastasis of oral squamous cell carcinoma.
Carcinoma
Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma.
Carcinoma, Ovarian Epithelial
Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions.
Carcinoma, Squamous Cell
Elevated levels of both microRNA 378 (miR-378) and kallikrein-related peptidase 4 (KLK4) mRNA are associated with an unfavorable prognosis in triple-negative breast cancer.
Colonic Neoplasms
Kallikrein-related peptidase 4: a new activator of the aberrantly expressed protease-activated receptor 1 in colon cancer cells.
Endometrial Neoplasms
Kallikrein 4 (KLK4), a new member of the human kallikrein gene family is up-regulated by estrogen and progesterone in the human endometrial cancer cell line, KLE.
Endometrial Neoplasms
Kallikrein 4 overexpression in endometrial carcinoma and upregulation by estrogen via mitogen-activated protein kinase signal pathway.
Endometriosis
Kallikrein-related peptidase 4 promotes migration and invasion of endometrial stromal cells in endometriosis by inducing epithelial-mesenchymal transition.
Hepatitis C
Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.
Hepatitis C
Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex.
Infections
Identification of a Highly Antigenic Region of Subtilisin-Like Serine Protease 1 for Serodiagnosis of Neospora caninum Infection.
Leukoencephalopathies
A Case of Cerebral Small Vessel Disease Related to a Heterozygous Nonsense Mutation in HTRA1.
Leukoencephalopathies
Genetically Confirmed CARASIL: Case Report with Novel HTRA1 Mutation and Literature Review.
Lupus Nephritis
Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4.
Lupus Nephritis
Role of miR-422a and kallikrein-related peptidase 4 implicated in the development of lupus nephritis. Do we work in this direction?
Mesothelioma, Malignant
Kallikrein 4 is expressed in malignant mesothelioma--further evidence for the histogenetic link between mesothelial and epithelial cells.
Neoplasm Metastasis
Kallikrein-related peptidase 4 contributes to the tumor metastasis of oral squamous cell carcinoma.
Neoplasm Metastasis
MiR-378a-5p inhibits angiogenesis of oral squamous cell carcinoma by targeting KLK4.
Neoplasm Metastasis
Prostate Cancer-Associated Kallikrein-Related Peptidase 4 Activates Matrix Metalloproteinase-1 and Thrombospondin-1.
Neoplasms
Characterization of kallikrein-related peptidase 4 (KLK4) mRNA expression in tumor tissue of advanced high-grade serous ovarian cancer patients.
Neoplasms
Comparative Temporospatial Expression Profiling of Murine Amelotin Protein during Amelogenesis.
Neoplasms
Direct progesterone receptor and indirect androgen receptor interactions with the kallikrein-related peptidase 4 gene promoter in breast and prostate cancer.
Neoplasms
Elevated levels of both microRNA 378 (miR-378) and kallikrein-related peptidase 4 (KLK4) mRNA are associated with an unfavorable prognosis in triple-negative breast cancer.
Neoplasms
Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer.
Neoplasms
Kallikrein 4 is expressed in malignant mesothelioma--further evidence for the histogenetic link between mesothelial and epithelial cells.
Neoplasms
Kallikrein-related peptidase 4 (KLK4) initiates intracellular signaling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression.
Neoplasms
Kallikrein-related peptidase 4 contributes to the tumor metastasis of oral squamous cell carcinoma.
Neoplasms
Kallikrein-related peptidase 4 gene (KLK4) in prostate tumors: Quantitative expression analysis and evaluation of its clinical significance.
Neoplasms
Kallikrein-related peptidase 4 promotes migration and invasion of endometrial stromal cells in endometriosis by inducing epithelial-mesenchymal transition.
Neoplasms
Kallikrein-related peptidase signaling in colon carcinoma cells: Targeting proteinase-activated receptors (PARs).
Neoplasms
KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer.
Neoplasms
MiR-378a-5p inhibits angiogenesis of oral squamous cell carcinoma by targeting KLK4.
Odontogenic Tumors
Kallikrein 4 and matrix metalloproteinase-20 immunoexpression in malignant, benign and infiltrative odontogenic tumors.
Ovarian Neoplasms
Characterization of kallikrein-related peptidase 4 (KLK4) mRNA expression in tumor tissue of advanced high-grade serous ovarian cancer patients.
Ovarian Neoplasms
Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment.
Pancreatic Neoplasms
PRSS1 mutations and the proteinase/antiproteinase imbalance in the pathogenesis of pancreatic cancer.
Pancreatitis
High Incidence of PRSS1 and SPINK1 Mutations in Korean Children With Acute Recurrent and Chronic Pancreatitis.
Pancreatitis, Chronic
High Incidence of PRSS1 and SPINK1 Mutations in Korean Children With Acute Recurrent and Chronic Pancreatitis.
Pancreatitis, Chronic
Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.
Pancreatitis, Chronic
Mutation That Promotes Activation of Trypsinogen Increases Severity of Secretagogue-Induced Pancreatitis in Mice.
Prostatic Neoplasms
Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms.
Prostatic Neoplasms
Crystal structure of the inhibitor-free form of the serine protease kallikrein-4.
Prostatic Neoplasms
Detection of human kallikrein 4 in healthy and cancerous prostatic tissues by immunofluorometry and immunohistochemistry.
Prostatic Neoplasms
Direct progesterone receptor and indirect androgen receptor interactions with the kallikrein-related peptidase 4 gene promoter in breast and prostate cancer.
Prostatic Neoplasms
Epithelial-mesenchymal transition in prostate cancer and the potential role of kallikrein serine proteases.
Prostatic Neoplasms
Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis.
Prostatic Neoplasms
Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.
Prostatic Neoplasms
Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells.
Prostatic Neoplasms
Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer.
Prostatic Neoplasms
Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer.
Prostatic Neoplasms
Kallikrein 4 is a proliferative factor that is overexpressed in prostate cancer.
Prostatic Neoplasms
Kallikrein-related peptidase 4 (KLK4) initiates intracellular signaling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression.
Prostatic Neoplasms
Kallikrein-related peptidase-4 initiates tumor-stroma interactions in prostate cancer through protease-activated receptor-1.
Prostatic Neoplasms
KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer.
Prostatic Neoplasms
Mastering the canonical loop of serine protease inhibitors: enhancing potency by optimising the internal hydrogen bond network.
Prostatic Neoplasms
Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: Implications for xenograft models of human prostate cancer.
Prostatic Neoplasms
Polyclonal antibodies against kallikrein-related peptidase 4 (KLK4): immunohistochemical assessment of KLK4 expression in healthy tissues and prostate cancer.
Prostatic Neoplasms
Potent, Selective, and Cell-Penetrating Inhibitors of Kallikrein-Related Peptidase 4 Based on the Cyclic Peptide MCoTI-II.
Prostatic Neoplasms
Prostate Cancer-Associated Kallikrein-Related Peptidase 4 Activates Matrix Metalloproteinase-1 and Thrombospondin-1.
Prostatic Neoplasms
Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4.
Sepsis
Identification of Potential Biomarkers by Serum Proteomics Analysis in Rats With Sepsis.
Squamous Cell Carcinoma of Head and Neck
Kallikrein-related peptidase 4 contributes to the tumor metastasis of oral squamous cell carcinoma.
Squamous Cell Carcinoma of Head and Neck
Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma.
Triple Negative Breast Neoplasms
Elevated levels of both microRNA 378 (miR-378) and kallikrein-related peptidase 4 (KLK4) mRNA are associated with an unfavorable prognosis in triple-negative breast cancer.
Triple Negative Breast Neoplasms
Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer.
Virus Diseases
Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.065
acetyl-FVQR-4-nitroanilide
pH 7.4, temperature not specified in the publication
0.0207
Z-FVR-p-nitroanilide
-
in 50 mM HEPES (pH 7.0), 150 mM NaCl, 10 mM CaCl2 buffer, at 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.64
Z-FVR-p-nitroanilide
-
in 50 mM HEPES (pH 7.0), 150 mM NaCl, 10 mM CaCl2 buffer, at 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.31
-
purified recombinant enzyme, substrate H-D-Val-L-Leu-L-Lys-4-nitroanilide
0.67
-
purified recombinant enzyme, substrate N-benzoyl-L-Ile-L-Glu-Gly-L-Arg-4-nitroanilide
1.12
-
purified recombinant enzyme, substrate H-D-Pro-L-Phe-L-Arg-4-nitroanilide
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
647338, 664270, 664273, 668144, 668285, 669814, 680174, 681390, 685946, 686322, 686543, 687699, 689848
-
-
brenda
-
SwissProt
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
downregulated expression in efussions compared to solid tumors, higher expression as compared to malignant mesothelioma
brenda
-
KLK4 endometrial mRNA expression is greatest on days 0, 5, and 10 when compared with days 12, 15, and 17 of the estrous cycle and greater in cyclic compared with pregnant gilts
brenda
KLK4 is highly expressed in ectopic endometrial stromal cells
brenda
-
mesothelioma cell of both peritoneal and pleural origin express K4, with downregulated expression in efussions compared to solid tumors
brenda
the expression of KLK4 is initiated from postnatal day 1 expressed in molar ameloblasts. From postnatal day 5 on, KLK4 is distributed not only in ameloblasts, but also in the degenerating satellite reticulum of molar enamel organ
brenda
KLK4 is differentially expressed in oral carcinomas. OSCC cell lines with high invasive and metastatic potential have the highest levels of KLK4 expression
brenda
-
co-expression of agonist and PAR-2 in primary prostate cancer (benign glands of benign prostatic hyperplasia, prostatic intraepithelial neoplasia and cancer) and prostate cancer bone metastasis
brenda
-
KLK4 protein is significantly overexpressed in malignant prostate compared with normal prostate. No significant differences in expression levels among well or poorly differentiated tumors
brenda
-
KLK4 mRNA and protein is not significantly changed in SaOs2 cells treated with conditioned media from either PC-3 cells or LNCaP cells. KLK4 mRNA is clearly increased following direct co-culture of SaOs2 cells with either PC-3 orLNCaP cells
brenda
additional information
breast carcinoma cell line, enzyme is upregulated by progetsins and androgens
brenda
prostate carcinoma cell line, enzyme is upregulated by androgens
brenda
-
KLK4 mRNA and protein is increased following treatment with conditioned media from SaOs-2 cells
brenda
-
abundance of K4 comparable to that in breast carcinoma, higher expression as compared to malignant mesothelioma
brenda
-
KLK4 induces loss of PAR-2 from the cell surface and receptor internalisation
brenda
-
KLK4 mRNA and protein is increased following treatment with conditioned media from SaOs-2 cells
brenda
restricted expression in hormonally responsive normal and neoplastic epithelial tissue, but not in prostate stromal constituents
brenda
-
enzyme expression is regulated by estrogen and progesterone in prostate cancer cells and overexpressed in prostate cancer
brenda
-
KLK4 is produced exclusively by the epithelial cancer cells
brenda
expression of human kallikrein 1-related peptidase 4 in prostate cancer patients with bone metastasis or advanced stage, immunohistochemic analysis of 62 prostate cancer samples
brenda
two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4. Kallikrein 4 is secreted by transition and maturation stage ameloblasts
brenda
-
expression of KLK4 is more intense in the stroma and uterine epithelium from days 0 to 10 of the estrous cycle
brenda
additional information
enzyme shows a prostate-restricted expression
brenda
additional information
no expression in stomach, heart, spleen, placenta, liver, pancrease, kidney, skeletal muscle, small intestine
brenda
additional information
-
no expression in stomach, heart, spleen, placenta, liver, pancrease, kidney, skeletal muscle, small intestine
brenda
additional information
enzyme expression is restricted to developimg teeth
brenda
additional information
-
enzyme expression is restricted to developimg teeth
brenda
additional information
-
conceptus tissue, KLK4 expression is greatest on day 10 with expression declining after day 14 of gestation
brenda
additional information
-
enzyme expression is restricted to developimg teeth
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
is predominantely nuclear in normal prostate epithelial cells
brenda
additional information
enzyme contains an amino-terminal pre-propeptide sequence, indicating a potential secretory function
-
brenda
additional information
-
enzyme contains an amino-terminal pre-propeptide sequence, indicating a potential secretory function
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
KLK4 dysfunction causes some types of developmental defect in enamel
metabolism
physiological function
metabolism
KLK4 activates matrix metalloproteinase-1, a protease that promotes prostate tumor growth and metastasis. It is a potential multifunctional regulator of prostate cancer progression
metabolism
coincidence of KLK4 and dipeptidyl-peptidase I distribution in ameloblasts strongly suggests that dipeptidyl-peptidase I activates KLK4
physiological function
-
kallikrein-related peptidase-4 (KLK4) initiates tumor-stroma interactions in prostate cancer through protease-activated receptor-1 (PAR-1). KLK4 triggers transmembrane signaling and upregulates interleukin-6 in WPMY-1 cells through PAR-1. Cancer epithelium produces KLK4 to activate PAR-1 in the surrounding stroma, which in-turn releases cytokines (interleukin-6) that stimulate cancer cells to proliferate and increase production of kallikreins
physiological function
the enzyme activates the hepatocyte growth factor, a multifunctional growth factor that plays an important role in cancer progression via its specific receptor tyrosine kinase MET, a c-met proto-oncogene product. Correlation between phospho-MET, MET, KLK4 expression and clinicopathological parameters, overview
physiological function
the enzyme substrate murine ephrin-B2 is glycosylated and this post-translational modification may regulate the enzyme cleavage activity
physiological function
the enzyme serves vital functions in dental enamel formation. KLK4 is involved in degradation of extracellular matrix proteins and it is thought that this proteolytic activity can also promote tumor invasion and metastasis. KLK4 expression is stronger in primary tumors that later either recurred or developed metastases, suggesting that its preferential expression in OSCC might contribute to individual tumor biology
physiological function
the enzyme plays a pivotal role during dental enamel formation by degrading the major enamel protein, amelogenin, prior to the final steps of enamel hardening. KLK4 binds hydroxyapatite directly
physiological function
KLK4 most likely plays a proteolytic role in degeneration of enamel organ
physiological function
KLK4 overexpression promotes proliferation and suppresses apoptosis of ectopic endometrial stromal cells, induces cell migration and invasion, and enhances angiogenesis in vivo. KLK4 overexpression mediates the protein cleavage of pro-brain-derived neurotrophic factor in ectopic endometrial stromal cells. Brain-derived neurotrophic factor is a vital downstream substrate of KLK4, maintains the proliferation, metastasis, and pro-angiogenesis abilities
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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). Q9XSN6_PIG
254
0
27235
TrEMBL
other Location (Reliability: 1)
KLK4_HUMAN
254
0
27032
Swiss-Prot
other Location (Reliability: 2)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
enzyme forms complexes with alpha1-antitrypsin, alpha2-antiplasmin and alpha2-macroglobulin
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
3 potential N-linked glycosylation sites: N134, N169, and N214 of the nucleotide sequence
glycoprotein
-
3 potential N-linked glycosylation sites: N134, N169, and N214 of the nucleotide sequence
-
proteolytic modification
-
recombinant chimeric enzyme with exchange of the pro-piece of the zymogen for that of prostate-specific antigen PSA to create an activation site suceptible for trypsin-type proteases proteolytically activates itself
proteolytic modification
KLK4 is secreted as an inactive zymogen, pro-KLK4
proteolytic modification
no activation of recombinant zymogen by native KLK4 enzyme in vitro
proteolytic modification
recombinant zymogen can be activated in vitro by thermolysin and by recombinant pig enamelysin
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by vapor diffusion in hanging drops. K4 crystallised in the presence of 10 mM Ni2+ reveals tetragonal space group P4. In the presence of Zn2+ it reveals tetragonal space group P41212. In the presence of 10 mM Co2+ it reveals monoclinic space group P21. The three different K4 crystal forms with bound Ni2+, Zn2, and Co2+ contain two, four and 16 crystallographically independent K4 molecules per asymmetric unit, respectively. K4 possesses an unusual 99-loop that creates a groove-like acidic S2 subsite
-
hanging drop vapour diffusion method using 20% PEG-MME 2000, 100 mM Tris (pH 8.5) and 10 mM NiCl2, or 100 mM HEPES (pH 6.5) and 100 mM NaCl with 1.6 M ammonium sulfate, or with 10 mM CoCl2, 100 mM Mes buffer (pH 6.0) and 1.6 M ammonium sulfate
-
strcture of inhibitor-free form of KLK4, to 1.64 A resolution. The crystals belong to space group P1, and contain four molecules in the asymmetric unit
structure in complex with Kunitz-type inhibitor BbKI, SwissProt ID P83052
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E77A
H25A
additional information
additional information
-
naturally occuring gene mutation G214A results in a truncated enzyme that lacks residue S207 of the catalytic triad. Mutation affects tooth enamel formation causing the enamel crystallites to grow incompletely in thickness or width but to normal length, i.e. autosomal recessive hypomaturation amelogenesis imperfecta
additional information
-
KLK-4 mutant (g.2142G>A), enamel is of normal thickness but opaque throughout its width compared with normal enamel. Enamel has a normal prismatic structure and generally a well-organized and discernable crystallite composition. In some areas, globular structures are present where crystallites are not discernable or appear to have an altered morphology. The KLK-4 mutant enamel has an increased protein content compared with normal enamel
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
nickel-nitrilotriacetic acid-Sepharose column chromatography and benzamidine-Sepharose column chromatography
recombinant chimeric enzyme after isolation from inclusion bodies and refolding
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
construction of a chimeric enzyme with exchange of the pro-piece of the zymogen for that of prostate-specific antigen PSA to create an activation site suceptible for trypsin-type proteases, expression in Escherichia coli strain BL21(DE3)
-
DNA sequence determination and analysis, chromosome mapping and genomic organization
DNA sequence determination and analysis, chromosome mapping and genomic organization, promotor analysis
expressed in Escherichia coli M15(pREP4) cells and in insect cells (nur hk5)
expression in Escherichia coli strain AD 494 (DE3) with and without the pro-peptide
expression in Spodoptera frugiperda SF9 cells via transfection with baculovirus
gene KLK4, coupling of the coding sequence of mature enzyme to the pro-domain of prostate specific antigen at the 5' end, and V5 and poly-histidine encoding sequences at the 3' end in plasmid pIBm recombinant expression as inactive zymogen in Spodoptera frugiperda insect cell line Sf9
into the BamH/HindIII restriction sites of the pQE30 vector and expressed in Escherichia coli M15[pREP4] cells
-
KLK4, 5, 6, and 7 full-length cDNA cloned into vector pRc/RSV. OV-MZ-6 ovarian cancer cells stably co-transfected with plasmids expressing K4-7. These OVKLK4+5+6+7 cells inoculated into the peritoneal cavity of nude mice
-
KLK4-pIB/V5-His construct expressed in Sf9 cells. PC-3 cell stimulated with KLK4
-
DNA sequence determination and analysis, chromosome mapping and genomic organization
DNA sequence determination and analysis, chromosome mapping and genomic organization
-
DNA sequence determination and analysis, chromosome mapping and genomic organization
DNA sequence determination and analysis, chromosome mapping and genomic organization, promotor analysis
DNA sequence determination and analysis, chromosome mapping and genomic organization, promotor analysis
Q9JIS2
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
kallikrein-related peptidase KLK4 expression is up-regulated in ectopic endometrium tissues of patients with endometriosis
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
isolation from inclusion bodies after recombinant expression in Escherichia coli, refolding with self-activation during the process
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
enzyme-specific sandwich-type immunoassay using a monoclonal antibody, detection limit is 0.02 microgram per liter, and less than 0.1% cross-reactivity with other human kallikreins
diagnostics
medicine
diagnostics
four-kallikrein panel is a prostate screening test. An important proportion number of men presenting for biopsy falls outside the diagnostic grey zone, having a positive digital rectal exam or prostate-specific antigen 10-25 ng/ml. The four kallikrein panel has good discrimination in these men, and use of the panel reduces biopsy rates in this group of men by over 20%. The use of the panel in men with positive digital rectal exam or prostate-specific antigen 10-25 is justified
medicine
-
patients with epithelial ovarian carcinoma, carcinoma cells expressed enzyme in 80% of effusions and 82% of solid tumors, levels are highest in effusions. Enzyme expression does not predict survival
medicine
-
naturally occuring gene mutation G214A results in a truncated enzyme that lacks residue S207 of the catalytic triad. Mutation affects tooth enamel formation causing the enamel crystallites to grow incompletely in thickness or width but to normal length, i.e. autosomal recessive hypomaturation amelogenesis imperfecta
medicine
-
no significant differences in enzyme protein content between healthy prostate tissue and malignant or benign prostate
medicine
-
KLK-4 proteinase is essential for the final crystallite growth of enamel but is not critical for crystallite orientation, prism formation or enamel thickness
medicine
-
KLK4 initiates Ca2+ mobilization via PAR-1 and PAR-2 but not via PAR-4. KLK4 has greater efficacy for initiating Ca2+ signalling via PAR-2 than PAR-1. Signals induced by KLK4 via PARs may be important in prostate cancer
medicine
-
K4 is not only expressed in prostate cancer cells, but also osteoblasts, in bone metastases. Thus, K4 may have proteolytic roles as a potential mediator of cellular interactions between prostate cancer and bone cells. Complex interactions may occur between prostate cancer and bone cells in the metastatic environment. Co-culture models are a crucial tool in evaluating cellular interactions
medicine
-
expression of the various tissue kallikreins like KLK4 in the endometrium and conceptus during the estrous cycle and early pregnancy in the pig can serve in the activation of growth factors and tissue remodeling during the establishment of pregnancy
medicine
-
KLK4 is a proliferative factor with effects on cell cycle-related gene expression. It may have an important role in prostate cancer development and progression
medicine
-
tumor-associated overexpression of tissue kallikreins contributes to ovarian cancer progression. OV-MZ-6 ovarian cancer cells simultaneously expressing K4-7 display similar proliferative capacity as the vector-transfected control cells, but show significantly increased invasive behavior. Simultaneous expression of K4-7 in OV-MZ-6 cells and inoculated into the peritoneum of nude mice, results in a remarkable 92% mean increase in tumor burden compared to control cell line
medicine
-
kallikrein 4 quantification serves as an independent biomarker for the discrimination between the malignant and the benign nature of prostate tumors
medicine
KLK4 can serve as a potential therapeutic target in patients with oral cancer. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines
medicine
kallikrein-related peptidase KLK4 expression is up-regulated in ectopic endometrium tissues of patients with endometriosis
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Homo sapiens (Q9Y5K2)
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 (Q9Y5K2)
brenda
Simmer, J.P.; Fukae, M.; Tanabe, T.; Yamakoshi, Y.; Uchida, T.; Xue, J.; Margolis, H.C.; Shimizu, M.; DeHart, B.C.; Hu, J.C.C.; Bartlett, J.D.
Purification, characterization, and cloning of enamel matrix serine proteinase 1
J. Dent. Res.
77
377-386
1998
Sus scrofa (Q9XSN6), Sus scrofa, Sus scrofa EMSP1 (Q9XSN6)
brenda
Yousef, G.M.; Obiezu, C.V.; Luo, L.Y.; Black, M.H.; Diamandis, E.P.
Prostase/KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated
Cancer Res.
59
4252-4256
1999
Homo sapiens (Q9Y5K2), Homo sapiens
brenda
Stephenson, S.A.; Verity, K.; Ashworth, L.K.; Clements, J.A.
Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4
J. Biol. Chem.
274
23210-23214
1999
Homo sapiens (Q9Y5K2)
brenda
Nelson, P.S.; Gan, L.; Ferguson, C.; Moss, P.; Gelinas, R.; Hood, L.; Wang, K.
Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression
Proc. Natl. Acad. Sci. USA
96
3114-3119
1999
Homo sapiens (Q9Y5K2), Homo sapiens
brenda
Hu, J.C.C.; Zhang, C.; Sun, X.; Yang, Y.; Cao, X.; Ryu, O.; Simmer, J.P.
Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors
Gene
251
1-8
2000
Homo sapiens (Q9Y5K2), Homo sapiens, Mus musculus (Q9JIS2), Mus musculus
brenda
Takayama, T.K.; McMullen, B.A.; Nelson, P.S.; Matsumura, M.; Fujikawa, K.
Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase
Biochemistry
40
15341-15348
2001
Homo sapiens
brenda
Ryu, O.; Hu, J.C.; Yamakoshi, Y.; Villemain, J.L.; Cao, X.; Zhang, C.; Bartlett, J.D.; Simmer, J.P.
Porcine kallikrein-4 activation, glycosylation, activity, and expression in prokaryotic and eukaryotic hosts
Eur. J. Oral Sci.
110
358-365
2002
Sus scrofa (Q9XSN6), Sus scrofa
brenda
Beaufort, N.; Debela, M.; Creutzburg, S.; Kellermann, J.; Bode, W.; Schmitt, M.; Pidard, D.; Magdolen, V.
Interplay of human tissue kallikrein 4 (hK4) with the plasminogen activation system: hK4 regulates the structure and functions of the urokinase-type plasminogen activator receptor (uPAR)
Biol. Chem.
387
217-222
2006
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
Davidson, B.; Xi, Z.; Klokk, T.I.; Trope, C.G.; D?rum, A.; Scheistr?en, M.; Saatcioglu, F.
Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions
Am. J. Clin. Pathol.
123
360-368
2005
Homo sapiens
brenda
Obiezu, C.V.; Michael, I.P.; Levesque, M.A.; Diamandis, E.P.
Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
Biol. Chem.
387
749-759
2006
Homo sapiens
brenda
Xi, Z.; Klokk, T.I.; Korkmaz, K.; Kurys, P.; Elbi, C.; Risberg, B.; Danielsen, H.; Loda, M.; Saatcioglu, F.
Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer
Cancer Res.
64
2365-2370
2004
Homo sapiens
brenda
Obiezu, C.V.; Shan, S.J.; Soosaipillai, A.; Luo, L.Y.; Grass, L.; Sotiropoulou, G.; Petraki, C.D.; Papanastasiou, P.A.; Levesque, M.A.; Diamandis, E.P.
Human kallikrein 4: quantitative study in tissues and evidence for its secretion into biological fluids
Clin. Chem.
51
1432-1442
2005
Homo sapiens
brenda
Hart, P.S.; Hart, T.C.; Michalec, M.D.; Ryu, O.H.; Simmons, D.; Hong, S.; Wright, J.T.
Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta
J. Med. Genet.
41
545-549
2004
Homo sapiens
brenda
Westermann, D.; Schultheiss, H.P.; Tschoepe, C.
New perspective on the tissue kallikrein-kinin system in myocardial infarction: role of angiogenesis and cardiac regeneration
Int. Immunopharmacol.
8
148-154
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 (Q9Y5K2)
brenda
Debela, M.; Magdolen, V.; Grimminger, V.; Sommerhoff, C.; Messerschmidt, A.; Huber, R.; Friedrich, R.; Bode, W.; Goettig, P.
Crystal structures of human tissue kallikrein 4: activity modulation by a specific zinc binding site
J. Mol. Biol.
362
1094-1107
2006
Homo sapiens
brenda
Fernando, S.C.; Buck, J.S.; Ashworth, M.D.; Ross, J.W.; Geisert, R.D.; DeSilva, U.
Porcine endometrial and conceptus tissue kallikrein 1, 4, 11, and 14 gene expression
Reproduction
132
939-947
2006
Sus scrofa
brenda
Klokk, T.I.; Kilander, A.; Xi, Z.; Waehre, H.; Risberg, B.; Danielsen, H.E.; Saatcioglu, F.
Kallikrein 4 is a proliferative factor that is overexpressed in prostate cancer
Cancer Res.
67
5221-5230
2007
Homo sapiens
brenda
Davidson, B.; Xi, Z.; Saatcioglu, F.
Kallikrein 4 is expressed in malignant mesothelioma--further evidence for the histogenetic link between mesothelial and epithelial cells
Diagn. Cytopathol.
35
80-84
2007
Homo sapiens
brenda
Wright, J.T.; Daly, B.; Simmons, D.; Hong, S.; Hart, S.P.; Hart, T.C.; Atsawasuwan, P.; Yamauchi, M.
Human enamel phenotype associated with amelogenesis imperfecta and a kallikrein-4 (g.2142G>A) proteinase mutation
Eur. J. Oral Sci.
114 Suppl 1; 13-7
discussion 39-41, 379
2006
Homo sapiens
brenda
Yamakoshi, Y.; Hu, J.C.; Fukae, M.; Yamakoshi, F.; Simmer, J.P.
How do enamelysin and kallikrein 4 process the 32-kDa enamelin?
Eur. J. Oral Sci.
114 Suppl 1; 45-51; discussion 93-5
379-80
2006
Sus scrofa
brenda
Ramsay, A.J.; Dong, Y.; Hunt, M.L.; Linn, M.; Samaratunga, H.; Clements, J.A.; Hooper, J.D.
Kallikrein-related peptidase (KLK) 4 initiates intracellular signalling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression
J. Biol. Chem.
283
12293-12304
2008
Homo sapiens
brenda
Gao, J.; Collard, R.L.; Bui, L.; Herington, A.C.; Nicol, D.L.; Clements, J.A.
Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer
Prostate
67
348-360
2007
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 (Q9Y5K2)
brenda
Lu, Y.; Papagerakis, P.; Yamakoshi, Y.; Hu, J.C.; Bartlett, J.D.; Simmer, J.P.
Functions of KLK4 and MMP-20 in dental enamel formation
Biol. Chem.
389
695-700
2008
Homo sapiens (Q9Y5K2)
brenda
Tye, C.E.; Pham, C.T.; Simmer, J.P.; Bartlett, J.D.
DPPI may activate KLK4 during enamel formation
J. Dent. Res.
88
323-327
2009
Homo sapiens (Q9Y5K2)
brenda
Wang, W.; Mize, G.J.; Zhang, X.; Takayama, T.K.
Kallikrein-related peptidase-4 initiates tumor-stroma interactions in prostate cancer through protease-activated receptor-1
Int. J. Cancer
126
599-610
2010
Homo sapiens
brenda
Avgeris, M.; Stravodimos, K.; Scorilas, A.
Kallikrein-related peptidase 4 gene (KLK4) in prostate tumors: quantitative expression analysis and evaluation of its clinical significance
Prostate
71
1780-1789
2011
Homo sapiens
brenda
Lisle, J.E.; Mertens-Walker, I.; Stephens, C.R.; Stansfield, S.H.; Clements, J.A.; Herington, A.C.; Stephenson, S.A.
Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: implications for xenograft models of human prostate cancer
Exp. Cell Res.
333
136-146
2015
Homo sapiens (Q9YSK2), Homo sapiens
brenda
Mukai, S.; Yorita, K.; Yamasaki, K.; Nagai, T.; Kamibeppu, T.; Sugie, S.; Kida, K.; Onizuka, C.; Tsukino, H.; Kamimura, T.; Kamoto, T.; Kataoka, H.
Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis
Hum. Cell
28
133-142
2015
Homo sapiens (Q9YSK2), Homo sapiens
brenda
Swedberg, J.E.; Ghani, H.A.; Harris, J.M.; de Veer, S.J.; Craik, D.J.
Potent, selective, and cell-penetrating inhibitors of kallikrein-related peptidase 4 based on the cyclic peptide MCoTI-II
ACS Med. Chem. Lett.
9
1258-1262
2018
Homo sapiens (Q9Y5K2), Homo sapiens
brenda
Papagerakis, P.; Pannone, G.; Zheng, L.I.; Athanassiou-Papaefthymiou, M.; Yamakoshi, Y.; McGuff, H.S.; Shkeir, O.; Ghirtis, K.; Papagerakis, S.
Clinical significance of kallikrein-related peptidase-4 in oral cancer
Anticancer Res.
35
1861-1866
2015
Homo sapiens (Q9Y5K2), Homo sapiens
brenda
Perez, V.; Mangum, J.; Hubbard, M.
Direct evidence that KLK4 is a hydroxyapatite-binding protein
Biochem. Biophys. Res. Commun.
495
1896-1900
2017
Homo sapiens (Q9Y5K2)
brenda
Yang, F.; Aubele, M.; Walch, A.; Gross, E.; Napieralski, R.; Zhao, S.; Ahmed, N.; Kiechle, M.; Reuning, U.; Dorn, J.; Sweep, F.; Magdolen, V.; Schmitt, M.
Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer
Biol. Chem.
398
1151-1164
2017
Homo sapiens (Q9Y5K2), Homo sapiens
brenda
Wang, L.; Xie, X.; Sun, Y.; Wang, J.; Wang, Y.; Wang, X.
KLK4 is synchronically expressed to CTSC in ameloblasts during amelogenesis molars
Int. J. Clin. Exp. Pathol.
10
5751-5757
2017
Mus musculus (Q9Z0M1)
-
brenda
Fuhrman-Luck, R.A.; Stansfield, S.H.; Stephens, C.R.; Loessner, D.; Clements, J.A.
Prostate cancer-associated kallikrein-related peptidase 4 activates matrix metalloproteinase-1 and thrombospondin-1
J. Proteome Res.
15
2466-2478
2016
Homo sapiens (Q9Y5K2)
brenda
Vickers, A.; Vertosick, E.A.; Sjoberg, D.D.; Roobol, M.J.; Hamdy, F.; Neal, D.; Bjartell, A.; Hugosson, J.; Donovan, J.L.; Villers, A.; Zappala, S.; Lilja, H.
Properties of the 4-kallikrein panel outside the diagnostic gray zone meta-analysis of patients with positive digital rectal examination or prostate specific antigen 10 ng/ml and above
J. Urol.
197
607-613
2017
Homo sapiens (Q9Y5K2)
brenda
Li, M.; Srp, J.; Mare, M.; Wlodawer, A.; Gustchina, A.
Structural studies of complexes of kallikrein 4 with wild-type and mutated forms of the Kunitz-type inhibitor BbKI
Acta Crystallogr. D Struct. Biol.
77
1084-1098
2021
Homo sapiens (Q9Y5K2)
brenda
Riley, B.T.; Hoke, D.E.; McGowan, S.; Buckle, A.M.
Crystal structure of the inhibitor-free form of the serine protease kallikrein-4
Acta Crystallogr. F Struct. Biol. Commun.
75
543-546
2019
Homo sapiens (Q9Y5K2)
brenda
Shi, J.; Qi, Y.; Sun, Y.; Huang, Y.
Kallikrein-related peptidase 4 promotes proliferation, migration, invasion, and pro-angiogenesis of endometrial stromal cells via regulation of brain-derived neurotrophic factor production in endometriosis
Am. J. Pathol.
194
121-134
2024
Homo sapiens (Q9Y5K2)
brenda
EXTERNAL LINKS (specific for EC-Number 3.4.21.B12)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
