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Information on EC 3.4.21.B6 - prostasin and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC3.4.21.B6preliminary BRENDA-supplied EC number
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EC Tree
3.4.21.B6 prostasinSpecify your search results
Word Map
- 3.4.21.B6
- matriptase
- aldosterone
- hai-1
- furin
-
gpi-anchored
- aprotinin
-
amiloride-sensitive
-
glycosylphosphatidylinositol-anchored
- hepsin
- nexin-1
-
kunitz-type
- camostat
- medicine
- profilaggrin
-
enac-mediated
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
prostasin, cap-1, prss8, cap1/prss8, channel-activating protease 1, channel activating protease 1, tracheal-prostasin, channel-activating protease-1, channel activating protease-1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CAP-1
PRSS8
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
157857-10-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-DHYR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-DHYR + 7-amino-4-carbamoylmethylcoumarin
-
suboptimal substrate
-
-
?
acetyl-KDYR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-KDYR + 7-amino-4-carbamoylmethylcoumarin
-
suboptimal substrate
-
-
?
acetyl-KHDR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-KHDR + 7-amino-4-carbamoylmethylcoumarin
-
suboptimal substrate
-
-
?
acetyl-KHYR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-KHYR + 7-amino-4-carbamoylmethylcoumarin
acetyl-PRLR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-PRLR + 7-amino-4-carbamoylmethylcoumarin
benzyloxycarbonyl-Gly-Pro-Arg-7-amido-4-trifluoromethylcoumarin
benzyloxycarbonyl-Gly-Pro-Arg + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
D-Phe-Phe-Arg-7-amido-4-methylcoumarin + H2O
D-Phe-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
D-Pro-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
-
fluorogenic substrate
-
?
D-Pro-Phe-Arg-7-amido-4-methylcoumarin + H2O
D-Pro-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
D-Val-Leu-Arg-7-amido-4-methylcoumarin + H2O
D-Val-Leu-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
human Toll-like receptor 4 + H2O
truncated Toll-like receptor 4 + ectodomain
reduction in the full-length form and reduction of the activation of the substrate. Substrate mutations K560A/K561A, K595A and R598A in the ectodomain abolish or reduce the enzyme activity, respectively
-
-
?
proform epithelial sodium channel + H2O
mature epithelial sodium channel + ?
-
-
-
?
proform G protein-coupled protease activated receptor-2 + H2O
mature G protein-coupled protease activated receptor-2 + ?
-
-
-
?
Toll-like receptor 4 + H2O
truncated Toll-like receptor 4 + ectodomain
reduction in the full-length form and reduction of the activation of the substrate
-
-
?
Z-Gly-Pro-Arg-7-amido-4-methylcoumarin + H2O
Z-Gly-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-KHYR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-KHYR + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
acetyl-KHYR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-KHYR + 7-amino-4-carbamoylmethylcoumarin
-
optimal substrate
-
-
?
acetyl-KHYR-7-amido-4-methylcoumarin + H2O
acetyl-KHYR + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-KHYR-7-amido-4-methylcoumarin + H2O
acetyl-KHYR + 7-amino-4-methylcoumarin
-
-
-
?
acetyl-PRLR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-PRLR + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
acetyl-PRLR-7-amido-4-carbamoylmethylcoumarin + H2O
acetyl-PRLR + 7-amino-4-carbamoylmethylcoumarin
-
suboptimal substrate
-
-
?
additional information
?
-
-
7-amido-4-carbamoylmethylcoumarin-KHYRIVAS-K(DNP)R completely inactive
-
-
?
additional information
?
-
critical role in the regulation of extracellular sodium ion transport via its activation of the epithelial cell sodium channel
-
-
?
additional information
?
-
-
critical role in the regulation of extracellular sodium ion transport via its activation of the epithelial cell sodium channel
-
-
?
additional information
?
-
-
active prostasin does not cleave the epidermal growth factor receptor extracellular domain directly, purified active prostasin also does not cleave purified epidermal growth factor receptor
-
-
?
additional information
?
-
activated prostasin appears to target several downstream effector proteins, including the epithelial sodium channel and the G protein-coupled protease activated receptor-2, which are both matriptase substrates
-
-
?
additional information
?
-
Lys or Arg residues are amino acids targeted by the enzyme
-
-
?
additional information
?
-
the matriptase zymogen is no substrate of prostasin
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
proform epithelial sodium channel + H2O
mature epithelial sodium channel + ?
-
-
-
?
proform G protein-coupled protease activated receptor-2 + H2O
mature G protein-coupled protease activated receptor-2 + ?
-
-
-
?
Toll-like receptor 4 + H2O
truncated Toll-like receptor 4 + ectodomain
reduction in the full-length form and reduction of the activation of the substrate
-
-
?
additional information
?
-
critical role in the regulation of extracellular sodium ion transport via its activation of the epithelial cell sodium channel
-
-
?
additional information
?
-
-
critical role in the regulation of extracellular sodium ion transport via its activation of the epithelial cell sodium channel
-
-
?
additional information
?
-
activated prostasin appears to target several downstream effector proteins, including the epithelial sodium channel and the G protein-coupled protease activated receptor-2, which are both matriptase substrates
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-3-phenyl-L-prolinamide
-
(3S)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-3-methyl-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-(cyclohexylmethoxy)-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-(cyclopentylmethoxy)-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-([[4-(methylsulfonyl)benzyl]carbamoyl]oxy)-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-hydroxy-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(4-chlorobenzyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(4-fluorobenzyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(4-methylbenzyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(dimethylcarbamoyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(morpholin-4-ylcarbonyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(phenylcarbamoyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(piperidin-1-ylcarbonyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(pyrrolidin-1-ylcarbonyl)oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[[3-(trifluoromethyl)benzyl]oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[[4-(trifluoromethyl)benzyl]oxy]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-4-(benzyloxy)-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-L-prolinamide
-
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-4-[(benzylcarbamoyl)oxy]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-L-prolinamide
-
bacterial lipopolysaccharide
viral promoter-driven expression of the human prostasin in the bladder of transgenic mice attenuates the bacterial lipopolysaccharide induction of nitric oxide synthase, whereas induction of cyclooxygenase-2, TNF-alpha, IL-1beta and IL-6 expression is not reduced
-
benzyl [(1S)-2-[[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-phenylpropyl]amino]-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]carbamate
-
benzyl [(1S)-5-amino-1-[[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-phenylpropyl]carbamoyl]pentyl]carbamate
-
camostat mesilate
-
potent inhibitor; potent prostasin inhibitor, 0.1 mM almost completely inhibits prostasin activity in vitro by 98.3%
N-[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-methylbutyl]-N2-[(benzyloxy)carbonyl]-L-lysinamide
-
N-[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-methylbutyl]-Nalpha-[(benzyloxy)carbonyl]-L-histidinamide
-
N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-L-prolinamide
-
spironolactone
-
decreases urinary prostasin in nomotensives in whom the renin/aldosterone axis is activated by a low Na+ intake, ineffective in individuals with high Na+ intake
additional information
-
not inhibited by alpha1-antitrypsin, alpha1-antitrypsinPDX, alpha1-antichymotrypsin, and soybean trypsin inhibitor
-
prostasin-binding protein
-
of mouse seminal vesicle fluid, binds covalently to prostasin, complete inhibition
-
Protease nexin-1
inhibits prostasin´s serine protease activity, capable of binding to membrane-anchored prostasin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
hepsin
-
hepsin activates prostasin by cleaving in the amino-terminal pro-peptide region of prostasin at Arg44
-
Ibuprofen
application of ibuprofen increases prostasin expression in the UROtsa and the B6Tert-1 cells. The ibuprofen-induced prostasin contributes to the formation and maintenance of the epithelial tight junctions in the B6Tert-1 cells. The matriptase zymogen wis down-regulated in the UROtsa cells by ibuprofen
transcription factor sterol regulatory element-binding protein-2
-
up-regulates protein expression
-
matriptase
-
matriptase activates prostasin by cleaving in the amino-terminal pro-peptide region of prostasin at Arg44
-
matriptase
-
prostasin activation is dependent on matriptase, prostasin activation is temporally coupled to matriptase autoactivation, prostatin activation is suppressed by matriptase knockdown and by blocking matriptase activation with sodium chloride
-
additional information
-
increases in urine of patients affected by primary aldosteronism after volume expansion
-
additional information
-
NP-40, Triton X-100, 15% glycerol, up to 0.5 mM DTT and 0.25 mM beta-mercaptoethanol have no effect on enzyme activity
-
additional information
prostasin mRNA expression in LNCaP cells is not responsive to dihydrotestosterone treatment
-
additional information
-
prostasin mRNA expression in LNCaP cells is not responsive to dihydrotestosterone treatment
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0335
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 801 expressed in Sf21 cells, glycosylated
0.0343
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 28 expressed in Escherichia coli, not glycosylated
0.0388
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 26 expressed in Escherichia coli, not glycosylated
0.04
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 40 expressed in Sf21 cells, not glycosylated
0.043
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 35 expressed in Sf21 cells, glycosylated
0.0493
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 1 expressed in mouse cells, glycosylated
827
D-Phe-Phe-Arg 7-amido-4-methylcoumarin
-
D-Phe-Phe-Arg-7-amido-4-methylcoumarin
108
D-Pro-Phe-Arg 7-amido-4-methylcoumarin
-
D-Pro-Phe-Arg-7-amido-4-methylcoumarin
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.12
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 26 expressed in Escherichia coli, not glycosylated
0.13
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 40 expressed in Sf21 cells, not glycosylated
0.14
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 28 expressed in Escherichia coli, not glycosylated
0.17
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 35 expressed in Sf21 cells, glycosylated
0.23
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 801 expressed in Sf21 cells, glycosylated
0.27
acetyl-KHYR-7-amido-4-methylcoumarin
pH 9, 23°C, variant 1 expressed in mouse cells, glycosylated
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000267
(3R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-3-phenyl-L-prolinamide
-
0.000049
(3S)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-3-methyl-L-prolinamide
-
0.000019
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-(cyclohexylmethoxy)-L-prolinamide
-
0.000065
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-(cyclopentylmethoxy)-L-prolinamide
-
0.000176
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-([[4-(methylsulfonyl)benzyl]carbamoyl]oxy)-L-prolinamide
-
0.00104
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-hydroxy-L-prolinamide
-
0.000012
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(4-chlorobenzyl)oxy]-L-prolinamide
-
0.000027
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(4-fluorobenzyl)oxy]-L-prolinamide
-
0.000045
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(4-methylbenzyl)oxy]-L-prolinamide
-
0.00155
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(dimethylcarbamoyl)oxy]-L-prolinamide
-
0.00051
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(morpholin-4-ylcarbonyl)oxy]-L-prolinamide
-
0.00013
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(phenylcarbamoyl)oxy]-L-prolinamide
-
0.000029
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(piperidin-1-ylcarbonyl)oxy]-L-prolinamide
-
0.000101
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[(pyrrolidin-1-ylcarbonyl)oxy]-L-prolinamide
-
0.000041
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[[3-(trifluoromethyl)benzyl]oxy]-L-prolinamide
-
0.000028
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-4-[[4-(trifluoromethyl)benzyl]oxy]-L-prolinamide
-
0.000049
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-4-(benzyloxy)-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-L-prolinamide
-
0.000065
(4R)-N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-4-[(benzylcarbamoyl)oxy]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-L-prolinamide
-
0.0021
benzyl [(1S)-2-[[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-phenylpropyl]amino]-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]carbamate
-
0.00578
benzyl [(1S)-5-amino-1-[[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-phenylpropyl]carbamoyl]pentyl]carbamate
-
0.0152
N-[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-methylbutyl]-N2-[(benzyloxy)carbonyl]-L-lysinamide
-
0.00572
N-[(1S)-1-[[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]carbamoyl]-3-methylbutyl]-Nalpha-[(benzyloxy)carbonyl]-L-histidinamide
-
0.0014
N-[(1S)-5-amino-1-(1,3-benzoxazol-2-ylcarbonyl)pentyl]-1-[(2R)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-L-prolinamide
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
co-expression of matriptase and its substrate serine protease prostasin
strong expression association between matriptase and its substrate prostasin in breast cancer
-
enzyme levels significantly higher than those in control cells
additional information
matriptase and prostasin display a near identical spatial expression pattern in the epithelial compartment of breast cancer tissue
-
prostasin is expressed at a relatively high level in human placental trophoblasts in early pregnant weeks
-
downregulation of the enzyme in high-grade prostate cancer as well as in invasive prostate cancer cells
-
prostasin is expressed at a relatively high level in human placental trophoblasts in early pregnant weeks
additional information
-
no activity in brain, muscle, testis, ventricle, atrium and aorta
additional information
-
natively expressed in JME/CF15 cells, cystic fibrosis airway epithelial cell line, little if any detectable in CHO cells and HEK-293 cells
additional information
expression of matriptase and prostasin in breast cancer cell lines, overview. No activity in MDA-MB-231 cells, SUM-159 cells, SUM-1315cells, and BT-549 cells
additional information
prostasin is co-expressed with matriptase and increases during human Caco-2 cell differentiation and barrier formation
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
-
loss of prostasin expression in the transitional cell carcinoma cell lines is correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation and may have functional implications in tumor invasion and resistance to chemotherapy
malfunction
-
prostasin silencing in BPH-1 cells is associated with up-regulation of iNOS, ICAM-1, interleukin-6, and interleukin-8, and down-regulation of cyclin D1, as well as reduced proliferation and invasion
metabolism
high-fat diet triggers the suppression of the enzyme expression by inducing endoplasmic reticulum stress and increases the Toll-like receptor 4 level in the liver. Serum enzyme levels are correlated to body mass index and homoeostasis model assessment-insulin resistance
metabolism
matriptase and not prostasin is the primary effector protease of tight junction assembly in simple columnar epithelia
physiological function
-
prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells. Prostasin participates in the proteolytic activation of epithelial sodium channel as well as cleavage of epidermal growth factor receptor extracellular domain in human epithelial cells. Prostasin functions as an invasion suppressor in human trophoblast, participating in the invasion-restrictive regulation of trophoblasts to avoid their over-penetration into the uterine wall
physiological function
-
prostasin is essential for terminal epithelial differentiation, prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor and is an invasion suppressor
physiological function
-
prostasin regulates human placental trophoblast cell proliferation via modulating the epidermal growth factor receptor-mitogen-activated protein kinase signaling pathway
physiological function
-
prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. Prostasin plays a negative regulatory role on protease-activated receptor-2-mediated signaling in prostate epithelial cell
physiological function
-
prostasin significantly increases both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner
physiological function
-
prostasin significantly increases both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Prostasin has a stimulatory effect on the aldosterone synthesis by adrenal gland through the nonproteolytic action
physiological function
Prostasin catalyzed activation of ENaC induces an open channel conformation associated with sodium influx that results in membrane depolarization. Prostasin together with matriptase comprise a single common proteolytic pathway,that is required for barrier formation. Prostasin is activated through proteolytic cleavage by matriptase, but prostasin is also required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway
physiological function
prostasin is also a regulator of the epidermal sodium channel like matriptase
physiological function
the serine protease prostasin regulates hepatic insulin sensitivity by modulating Toll-like receptor 4-mediated signalling, the enzyme decreases TLR4 levels by the proteolytic shedding
physiological function
HAI-1 but not HAI-2 is the prominent inhibitor for prostasin and matriptase in skin. The limited role for HAI-2 in the inhibition of matriptase and prostasin is the result of its primarily intracellular localization in basal and spinous layer keratinocytes, which probably prevents the HAI-2 from interacting with active prostasin or matriptase
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
27879
1 * 27879, refolded and purified prostasin variant 26, calculated from sequence
28351
1 * 28351, refolded and purified prostasin variant 28, calculated from sequence
40000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
monomer
1 * 27879, refolded and purified prostasin variant 26, calculated from sequence
monomer
1 * 28351, refolded and purified prostasin variant 28, calculated from sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
matriptase is an effective activator of the prostasin zymogen through direct proteolytic cleavage at its zymogen activation site. Prostasin is required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway
proteolytic modification
the prostasin zymogen is incapable of auto-activation and requires proteolytic processing by matriptase for conversion into an active protease
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method. Active prostasin is crystallized, and the structure is determined to 1.45 A resolution. These apoprotein crystals are soaked with nafamostat, allowing the structure of the inhibited acyl-enzyme intermediate structure to be determined to 2.0 A resolution
structure of the extracellular portion of the membrane associated serine protease solved to high resolution in complex with a nonselective d-FFR chloromethyl ketone inhibitor, in an apo form, in a form where the apo crystal is soaked with the covalent inhibitor camostat and in complex with the protein inhibitor aprotinin. It is also crystallized in the presence of the divalent cation Ca2+
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
prostasin gene silencing, drops epithelial Na+ channel currents to 26% of baseline
additional information
prostasin mutant does not manifest the nitric oxide synthase induction attenuation phenotype
additional information
-
prostasin mutant does not manifest the nitric oxide synthase induction attenuation phenotype
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by sequential anion exchange and aprotinin affinity chromatography, by Ni-NTA His-bind chromatography
-
DEAE Sepharose column chromatography, and hepatocyte growth factor activator inhibitor-1 mAb M19 immunoaffinity column chromatography
-
Ni-Sepharose column chromatography, HiTrap Q column chromatography, and Supderdex 200 gel filtration
-
Ni-Sepharose column chromatography, HiTrap Q column chromatography, and Superdex 200 gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293 cells
expression of the prostasin proenzyme in Escherichia coli as insoluble inclusion bodies, refolding and activating via proteolytic removal of the N-terminal propeptide
into pCRT7/NT-TOPO and expressed in Escherichia coli BL21(DE3)pLysS, into pcDNA3.1/V5-His-TOPO and expressed in CHO cells and HEK-293 cells, overexpression in CF epithelial cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
application of ibuprofen increases prostasin expression in the UROtsa and the B6Tert-1 cells
high-fat diet triggers the suppression of the enzyme expression by inducing endoplasmic reticulum stress
prostasin expression increases during human Caco-2 cell differentiation and barrier formation
prostasin is down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines
-
the mRNA level of prostasin is slightly but significantly decreased in both mild/moderate dysplasia and severe dysplasia and in carcinomas compared to normal tissue from the same individual
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
blood-borne RT-PCR amplification of prostasin transcripts may provide an early diagnosis of disseminated disease in patients with organ-confined carcinoma
medicine
-
is a major regulator of epithelial Na+ channel-mediated Na+ current, airway prostasin is a target for therapeutic inhibition to normalize ion current in cystic fibrosis airway
medicine
promoter DNA methylation partly causes the prostasin down-regualtion in prostate cancer cell lines
medicine
genetic variation of the prostasin gene may be implicated in the development of hypertension in youths
medicine
matriptase and prostasin mRNA levels are significantly reduced in colonic tissues from patients with both ulcerative colitis and Crohn's disease
medicine
patients with dengue fever show relatively low expression of prostasin and compared with healthy individuals and a high correlation of prostasin expression and DENV-2 RNA copy number. Dengue virus infection significantly decreases prostasin RNA levels of in vivo and in vitro models
medicine
prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances are not different in placental tissue between patients with preeclampsia and healthy pregnant women. Prostasin mRNA in placenta correlates directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels do not differ between groups. Preeclamptic patients show significantly elevated levels of prostasin in urine that correlates with urine albumin
medicine
PRSS8 is expressed in ovarian cancer at levels more than 100fold greater than in normal or benign ovarian lesions. Overexpression is found in early stages of ovarian cancer and is maintained in higher stages and grades of ovarian cancer. The PRSS8 overexpression is specific for ovarian cancer and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpress PRSS8. Overexpression of prostasin is largely localized to tumor epithelium and is absent in neighboring stroma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yu, J.X.; Chao, L.; Chao, J.
Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland
J. Biol. Chem.
269
18843-18848
1994
Homo sapiens
Chen, L.M.; Skinner, M.L.; Kauffman, S.W.; Chao, J.; Chao, L.; Thaler, C.D.; Chai, K.X.
Prostasin is a glycosylphosphatidylinositol-anchored active serine protease
J. Biol. Chem.
276
21434-21442
2001
Homo sapiens
Tong, Z.; Illek, B.; Bhagwandin, V.J.; Verghese, G.M.; Caughey, G.H.
Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line
Am. J. Physiol. Lung Cell Mol. Physiol.
287
L928-L935
2004
Homo sapiens
Chen, L.M.; Wang, C.; Chen, M.; Marcello, M.R.; Chao, J.; Chao, L.; Chai, K.X.
Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation
Am. J. Physiol. Renal Physiol.
291
F567-F577
2006
Homo sapiens (Q16651), Homo sapiens, Mus musculus
Shipway, A.; Danahay, H.; Williams, J.A.; Tully, D.C.; Backes, B.J.; Harris, J.L.
Biochemical characterization of prostasin, a channel activating protease
Biochem. Biophys. Res. Commun.
324
953-963
2004
Homo sapiens
Chao, J.
Prostasin
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , Eds. ) Academic Press
2
1708-1709
2004
Homo sapiens, Mus musculus, Rattus norvegicus, Xenopus laevis
-
Olivieri, O.; Castagna, A.; Guarini, P.; Chiecchi, L.; Sabaini, G.; Pizzolo, F.; Corrocher, R.; Righetti, P.G.
Urinary prostasin: a candidate marker of epithelial sodium channel activation in humans
Hypertension
46
683-688
2005
Homo sapiens
Chen, L.M.; Zhang, X.; Chai, K.X.
Regulation of prostasin expression and function in the prostate
Prostate
59
1-12
2004
Homo sapiens (Q16651)
Myerburg, M.M.; McKenna, E.E.; Luke, C.J.; Frizzell, R.A.; Kleyman, T.R.; Pilewski, J.M.
Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis
Am. J. Physiol. Lung Cell Mol. Physiol.
294
L932-L941
2008
Homo sapiens
Chen, M.; Chen, L.M.; Chai, K.X.
Mechanisms of sterol regulatory element-binding protein-2 (SREBP-2) regulation of human prostasin gene expression
Biochem. Biophys. Res. Commun.
346
1245-1253
2006
Homo sapiens
Chen, M.; Fu, Y.; Lin, C.; Chen, L.; Chai, K.X.
Prostasin induces protease-dependent and independent molecular changes in the human prostate carcinoma cell line PC-3
Biochim. Biophys. Acta
1773
1133-1140
2007
Homo sapiens
Chen, M.; Chen, L.; Chai, K.X.
Androgen regulation of prostasin gene expression is mediated by sterol-regulatory element-binding proteins and SLUG
Prostate
66
911-920
2006
Homo sapiens (Q16651), Homo sapiens
Zhu, H.; Guo, D.; Li, K.; Yan, W.; Tan, Y.; Wang, X.; Treiber, F.A.; Chao, J.; Snieder, H.; Dong, Y.
Prostasin: a possible candidate gene for human hypertension
Am. J. Hypertens.
21
1028-1033
2008
Homo sapiens (Q16651), Homo sapiens
Tully, D.C.; Vidal, A.; Chatterjee, A.K.; Williams, J.A.; Roberts, M.J.; Petrassi, H.M.; Spraggon, G.; Bursulaya, B.; Pacoma, R.; Shipway, A.; Schumacher, A.M.; Danahay, H.; Harris, J.L.
Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design
Bioorg. Med. Chem. Lett.
18
5895-5899
2008
Homo sapiens (Q16651)
Rickert, K.W.; Kelley, P.; Byrne, N.J.; Diehl, R.E.; Hall, D.L.; Montalvo, A.M.; Reid, J.C.; Shipman, J.M.; Thomas, B.W.; Munshi, S.K.; Darke, P.L.; Su, H.P.
Structure of human prostasin, a target for the regulation of hypertension
J. Biol. Chem.
283
34864-34872
2008
Homo sapiens (Q16651), Homo sapiens
Spraggon, G.; Hornsby, M.; Shipway, A.; Tully, D.C.; Bursulaya, B.; Danahay, H.; Harris, J.L.; Lesley, S.A.
Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations
Protein Sci.
18
1081-1094
2009
Homo sapiens (Q16651), Homo sapiens
Selzer-Plon, J.; Bornholdt, J.; Friis, S.; Bisgaard, H.C.; Lothe, I.M.; Tveit, K.M.; Kure, E.H.; Vogel, U.; Vogel, L.K.
Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
BMC Cancer
9
201
2009
Homo sapiens
Chen, L.; Verity, N.; Chai, K.
Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT)
BMC Cancer
9
377
2009
Homo sapiens
Costa, F.P.; Batista, E.L.; Zelmanowicz, A.; Svedman, C.; Devenz, G.; Alves, S.; Silva, A.S.; Garicochea, B.
Prostasin, a potential tumor marker in ovarian cancer--a pilot study
Clinics (Sao Paulo)
64
641-644
2009
Homo sapiens
Ma, X.J.; Fu, Y.Y.; Li, Y.X.; Chen, L.M.; Chai, K.; Wang, Y.L.
Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells
Histochem. Cell Biol.
132
639-646
2009
Homo sapiens
Fu, Y.Y.; Gao, W.L.; Chen, M.; Chai, K.X.; Wang, Y.L.; Chen, L.M.
Prostasin regulates human placental trophoblast cell proliferation via the epidermal growth factor receptor signaling pathway
Hum. Reprod.
25
623-632
2010
Homo sapiens
Chen, Y.W.; Wang, J.K.; Chou, F.P.; Chen, C.Y.; Rorke, E.A.; Chen, L.M.; Chai, K.X.; Eckert, R.L.; Johnson, M.D.; Lin, C.Y.
Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 (HAI-1) during epidermal differentiation
J. Biol. Chem.
285
31755-31762
2010
Homo sapiens
Ko, T.; Kakizoe, Y.; Wakida, N.; Hayata, M.; Uchimura, K.; Shiraishi, N.; Miyoshi, T.; Adachi, M.; Aritomi, S.; Konda, T.; Tomita, K.; Kitamura, K.
Regulation of adrenal aldosterone production by serine protease prostasin
J. Biomed. Biotechnol.
2010
793843
2010
Homo sapiens
Chen, M.; Chen, L.M.; Lin, C.Y.; Chai, K.X.
Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor
Mol. Cell. Biochem.
337
259-266
2010
Homo sapiens
Chen, L.M.; Hatfield, M.L.; Fu, Y.Y.; Chai, K.X.
Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells
Prostate
69
1790-1801
2009
Homo sapiens
Bergum, C.; Zoratti, G.; Boerner, J.; List, K.
Strong expression association between matriptase and its substrate prostasin in breast cancer
J. Cell. Physiol.
227
1604-1609
2012
Homo sapiens (Q16651)
Buzza, M.S.; Martin, E.W.; Driesbaugh, K.H.; Desilets, A.; Leduc, R.; Antalis, T.M.
Prostasin is required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway
J. Biol. Chem.
288
10328-10337
2013
Homo sapiens (Q16651)
Uchimura, K.; Hayata, M.; Mizumoto, T.; Miyasato, Y.; Kakizoe, Y.; Morinaga, J.; Onoue, T.; Yamazoe, R.; Ueda, M.; Adachi, M.; Miyoshi, T.; Shiraishi, N.; Ogawa, W.; Fukuda, K.; Kondo, T.; Matsumura, T.; Araki, E.; Tomita, K.; Kitamura, K.
The serine protease prostasin regulates hepatic insulin sensitivity by modulating TLR4 signalling
Nat. Commun.
5
3428
2014
Homo sapiens (Q16651), Mus musculus (Q9ESD1)
Chai, A.C.; Robinson, A.L.; Chai, K.X.; Chen, L.M.
Ibuprofen regulates the expression and function of membrane-associated serine proteases prostasin and matriptase
BMC Cancer
15
1025
2015
Homo sapiens (Q16651), Homo sapiens
Buzza, M.S.; Johnson, T.A.; Conway, G.D.; Martin, E.W.; Mukhopadhyay, S.; Shea-Donohue, T.; Antalis, T.M.
Inflammatory cytokines down-regulate the barrier-protective prostasin-matriptase proteolytic cascade early in experimental colitis
J. Biol. Chem.
292
10801-10812
2017
Homo sapiens (Q16651), Homo sapiens, Mus musculus (Q9ESD1)
Frederiksen-Moeller, B.; Joergensen, J.S.; Hansen, M.R.; Krigslund, O.; Vogel, L.K.; Andersen, L.B.; Jensen, B.L.
Prostasin and matriptase (ST14) in placenta from preeclamptic and healthy pregnant women
J. Hypertens.
34
298-306
2016
Homo sapiens (Q16651), Homo sapiens
Lin, C.K.; Tseng, C.K.; Wu, Y.H.; Lin, C.Y.; Huang, C.H.; Wang, W.H.; Liaw, C.C.; Chen, Y.H.; Lee, J.C.
Prostasin impairs epithelial growth factor receptor activation to suppress Dengue virus propagation
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219
1377-1388
2019
Homo sapiens (Q16651), Homo sapiens, Mus musculus (Q9ESD1)
Tamir, A.; Gangadharan, A.; Balwani, S.; Tanaka, T.; Patel, U.; Hassan, A.; Benke, S.; Agas, A.; DAgostino, J.; Shin, D.; Yoon, S.; Goy, A.; Pecora, A.; Suh, K.
The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer
J. Ovarian Res.
9
20
2016
Homo sapiens (Q16651), Homo sapiens
Lee, S.P.; Kao, C.Y.; Chang, S.C.; Chiu, Y.L.; Chen, Y.J.; Chen, M.G.; Chang, C.C.; Lin, Y.W.; Chiang, C.P.; Wang, J.K.; Lin, C.Y.; Johnson, M.D.
Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
PLoS ONE
13
e0192632
2018
Homo sapiens (Q16651), Homo sapiens
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