Information on EC 3.4.23.3 - gastricsin

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
3.4.23.3
-
RECOMMENDED NAME
GeneOntology No.
gastricsin
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
more restricted specificity than pepsin A, but shows preferential cleavage at Tyr-/- bonds. High activity on hemoglobin
show the reaction diagram
-
-
-
-
more restricted specificity than pepsin A, but shows preferential cleavage at Tyr-/- bonds. High activity on hemoglobin
show the reaction diagram
acid endopeptidase
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
endopeptidase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
parapepsin II
-
-
pepsin C
-
-
-
-
pepsin C
-
-
pepsin C
-
-
pepsin II
-
-
pepsinogen C
P20142
-
PGC
P20142
-
pig parapepsin II
-
-
-
-
progastricsin
P20142
-
seminal pepsin
-
-
EC 3.4.4.22
-
-
formerly
-
additional information
-
the enzyme belongs to the A1 peptidase family
CAS REGISTRY NUMBER
COMMENTARY
9012-71-9
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
P20142
the major useful function of progastricsin (PGC) includes production of pro-antimicrobial substance in seminal plasma. The action of PGC in the stomach is to degrade dietary proteins. However, in seminal fluid, it activates defensins for local antimicrobial defense. On the other hand, intracellular proprotein activation by PGC in acidic organelle, such as in proSP-B proteolysis, is important on the processing in the secretory pathway of alveolar type-2 cells
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-Ala-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
very low activity
-
-
?
acetyl-Ala-Leu-Val-His-OH + H2O
?
show the reaction diagram
-
very low activity
-
-
?
acetyl-Ala-Phe-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Ala-Phe-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Phe-Leu-Val-His methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Phe-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Phe-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Tyr-Leu-Val-His methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Tyr-Leu-Val-His methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Tyr-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Tyr-Leu-Val-His-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Tyr-Leu-Val-His-OH + H2O
?
show the reaction diagram
-
-
-
-
?
Albumin + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
acid denatured hemoglobin
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
pepsin C1 and C2
-
-
?
insulin B chain + H2O
?
show the reaction diagram
-
cleavage of sites Leu15-Tyr16 and Tyr16-Leu17
-
-
?
N-acetyl-L-phenylalanyl-L-diiodotyrosine + H2O
?
show the reaction diagram
-
-
-
-
?
N-acetyl-L-phenylalanyl-L-diiodotyrosine + H2O
?
show the reaction diagram
-
weak activity
-
-
?
N-acetyl-L-phenylalanyl-L-diiodotyrosine + H2O
?
show the reaction diagram
-
scarcely hydrolyzed
-
-
?
oxidized insulin B chain + H2O
?
show the reaction diagram
-
major site of attack are the bonds Tyr16-Leu17, 86%, Phe24-Phe25, 82%, His10-Leu11, 46%, Ala14-Leu15, 44%, Gly13-Ala14, 34%
-
-
?
oxidized insulin B chain + H2O
?
show the reaction diagram
-
pepsin C-1
-
-
?
Oxidized insulin B-chain + H2O
?
show the reaction diagram
-
-
-
?
Pro-Thr-Glu-Phe-(NO2)Phe-Arg-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
Pro-Thr-Glu-Phe-(NO2)Phe-Arg-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
reduced and carboxymethylated ribonuclease A + H2O
?
show the reaction diagram
-
-
-
?
Leu-Ser-(4-nitro)Phe-norleucine-Ala-Leu methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
clotting activity with kappa-casein is only half of that of chymosin and pepsin A
-
-
-
additional information
?
-
-
progastricsin is responsible for the autoproteolysis of seminal fluid proteins under acidic conditions. This suggests that the function of the enzyme is to degrade seminal fluid proteins deposited in the vagina, this in turn may decrease the antigenic load in the vagina and prevent immuno-infertility
-
-
-
additional information
?
-
-
transcriptional regulation of the pepsinogen C gene, presence of a DNA-binding protein that specifically binds to the promoter region of the rat pepsinogen C gene
-
-
-
additional information
?
-
-
pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases
-
-
-
additional information
?
-
-
the enzyme shows very high gastric antibacterial efficiency against Helicobacter pylori at pH 2.0
-
-
-
additional information
?
-
-
role of this gastric digestive enzyme in the regulation of food intake
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
progastricsin is responsible for the autoproteolysis of seminal fluid proteins under acidic conditions. This suggests that the function of the enzyme is to degrade seminal fluid proteins deposited in the vagina, this in turn may decrease the antigenic load in the vagina and prevent immuno-infertility
-
-
-
additional information
?
-
-
transcriptional regulation of the pepsinogen C gene, presence of a DNA-binding protein that specifically binds to the promoter region of the rat pepsinogen C gene
-
-
-
additional information
?
-
-
pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases
-
-
-
additional information
?
-
-
the enzyme shows very high gastric antibacterial efficiency against Helicobacter pylori at pH 2.0
-
-
-
additional information
?
-
-
role of this gastric digestive enzyme in the regulation of food intake
-
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,2-epoxy-(p-nitrophenoxy)propane
-
-
1,2-epoxy-3-(p-nitrophenoxy)propane
-
-
Acetyl-Phe
-
hydrolysis of acetyl-Phe-Leu-Val-His-amide
alpha2-Macroglobulin
-
activity with reduced and carboxymethylated ribonuclease A is significantly inhibited, activity with oxidized insulin B-chain is scarcely inhibited
-
Diazoacetyl-DL-norleucine methyl ester
-
-
Diazoacetyl-DL-norleucine methyl ester
-
-
isovaleryl pepstatin
-
-
-
L-363,564
-
a statyl peptide based on renin substrate angiotensinogen
L-364099
-
-
-
p-Bromophenylacyl bromide
-
-
Pepstatin
-
100 molar excess amount is needed for the complete inhibition of activity of pepsin C-1 and C-2
Pepstatin
-
-
Pepstatin
-
needs about 100fold molar excess for complete inhibition
pepstatin A
-
-
[1S-(1R*,2R*,3S*)]-[N-(4-morpholinylsulfonyl)-L-phenylalanyl]-N-[1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl]-4,5-didehydro-L-norvalinamide
-
-
-
[1S-(1R*,2R*,4S*)]-[N-(4-morpholinylsulfonyl)-L-phenylalanyl]-N-[1-(cyclohexylmethyl)-2,4-dihydroxy-5-methylhexyl]-4,5-didehydro-L-norvalinamide
-
-
-
[1S-[1R*[R*(R*)],2R*,4S*]]-[N-(4-morpholinylsulfonyl)-L-phenylalanyl]-N-[1-(cyclohexylmethyl)-2,4-dihydroxyhexyl]-N6-[(methylamino)thioxomethyl]-L-lysinamide
-
-
-
Lactoyl-pepstatin
-
very weakly
-
additional information
-
the pepsin C activity decreases due to its autocatalytical activity
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.51
-
acetyl-Ala-Phe-Leu-Val-His-NH2
-
-
0.7
-
acetyl-Ala-Phe-Leu-Val-His-NH2
-
-
1.84
-
acetyl-Phe-Leu-Val-His methyl ester
-
-
1.84
-
acetyl-Phe-Leu-Val-His-NH2
-
-
2.76
-
acetyl-Phe-Leu-Val-His-NH2
-
-
0.28
-
acetyl-Tyr-Leu-Val-His methyl ester
-
-
0.28
-
acetyl-Tyr-Leu-Val-His methyl ester
-
Km-value for the range 0.025-0.15 mM
1.71
-
acetyl-Tyr-Leu-Val-His methyl ester
-
Km-value for the range 0.025-1.0 mM
0.82
-
acetyl-Tyr-Leu-Val-His-NH2
-
-
0.82
-
acetyl-Tyr-Leu-Val-His-NH2
-
Km-value for the range 0.1-0.5 mM
4.31
-
acetyl-Tyr-Leu-Val-His-NH2
-
Km-value for the range 0.1-2.0 mM
0.82
-
acetyl-Tyr-Leu-Val-His-OH
-
-
0.098
-
Pro-Thr-Glu-Phe-(NO2)Phe-Arg-Leu
-
-
0.42
-
Pro-Thr-Glu-Phe-(NO2)Phe-Arg-Leu
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.3
-
acetyl-Ala-Phe-Leu-Val-His-NH2
-
-
7.01
-
acetyl-Ala-Phe-Leu-Val-His-NH2
-
-
5.13
-
acetyl-Phe-Leu-Val-His methyl ester
-
-
0.6
-
acetyl-Phe-Leu-Val-His-NH2
-
-
6.12
-
acetyl-Phe-Leu-Val-His-NH2
-
-
1.06
-
acetyl-Tyr-Leu-Val-His methyl ester
-
-
1.06
-
acetyl-Tyr-Leu-Val-His methyl ester
-
Km-value for the range 0.025-0.15 mM
5.76
-
acetyl-Tyr-Leu-Val-His methyl ester
-
Km-value for the range 0.025-1.0 mM
1.07
-
acetyl-Tyr-Leu-Val-His-NH2
-
-
1.07
-
acetyl-Tyr-Leu-Val-His-NH2
-
Km-value for the range 0.1-0.5 mM
1.08
-
acetyl-Tyr-Leu-Val-His-NH2
-
-
4.45
-
acetyl-Tyr-Leu-Val-His-NH2
-
Km-value for the range 0.1-2.0 mM
55
-
Pro-Thr-Glu-Phe-(NO2)Phe-Arg-Leu
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2
3
-
hemoglobin
3
-
-
hemoglobin
3.2
-
-
-
5
-
-
assay at
additional information
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1.1
4
-
pH 1.1: about 60% of maximal activity, pH 4.0: about 35% of maximal activity
1.2
3.5
-
pH 1.2: about 75% of maximal activity, pH 3.5: about 55% of maximal activity
1.3
4.5
-
pH 1.3: about 75% of maximal activity, pH 4.5: about 35% of maximal activity, pepsin C-2
1.4
4.5
-
pH 1.4: about 90% of maximal activity, pH 4.5: about 40% of maximal activity, pepsin C-1
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.4
-
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
the enzyme is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland
Manually annotated by BRENDA team
-
pepsinogen C transcript is first detected at 41 days post hatching and continuously expressed through to adult fish
Manually annotated by BRENDA team
-
pepsinogen C transcript is first detected at 41 days post hatching and continuously expressed through to adult fish
Manually annotated by BRENDA team
-
pepsinogen C transcript is first detected at 41 days post hatching and continuously expressed through to adult fish
Manually annotated by BRENDA team
-
pepsinogen C transcript is first detected at 41 days post hatching and continuously expressed through to adult fish
Manually annotated by BRENDA team
-
progastricsin mRNA copy number is downregulated under conditions of negative energy balance, such as starvation, and upregulated during positive energy balance, such as refeeding. Role of the enzyme in the regulation of food intake
Manually annotated by BRENDA team
-
primarily distributed in. Pepsinogen C transcript is first detected at 41 days post hatching and continuously expressed through to adult fish
Manually annotated by BRENDA team
-
pepsinogen C transcript is first detected at 41 days post hatching and continuously expressed through to adult fish
Manually annotated by BRENDA team
additional information
-
no expression in healthy breast tissue, reabsorption of zymogen from serum into kidney
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
in gastric juice, vaginal fluid, serum, and seminal plasma, no secretion in urine
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
27000
-
-
the MW of pepsinogen C is 35000 Da, gel filtration
32800
-
-
gel filtration
35460
-
-
calculation from nucleotide sequence; electrospray mass spectrometry
41400
-
-
calculation from amino acid composition
additional information
-
-
amino acid sequence, 24 residues, near the amino terminus
additional information
-
-
pepsinogen C-1, 39000 Da, SDS-PAGE; pepsinogen C-2, 41000 Da, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 39000, pepsinogen C-1 and pepsinogen C-2, SDS-PAGE
?
-
x * 41206, calculation from nucleotide sequence
?
P20142
x * 40000, calculated from amino acid sequence
additional information
-
secondary and tertiary structure determination
additional information
-
structure determination
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
pepsinogen C-1 and C-2
proteolytic modification
-
zymogen: progastricsin
proteolytic modification
-
progastricsin, MW 34000 Da is converted by acid activation to gastricsin, 31000 Da; zymogen: progastricsin
proteolytic modification
-
-
proteolytic modification
-
zymogen: pepsinogen C
proteolytic modification
-
the pepsin C activity decreases due to its autocatalytical activity
proteolytic modification
-
the zymogen pepsinogen C is activated after secretion
no modification
-
contains no carbohydrate
proteolytic modification
-
zymogen: pepsinogen C
proteolytic modification
-
the zymogen pepsinogen C is activated after secretion
proteolytic modification
-
zymogen: pepsinogen C
proteolytic modification
-
pepsinogen C-1 and C-2, each pepsinogen is converted to pepsin through an intermediate form under acidic conditions
side-chain modification
-
pepsinogen C-2 contains an Asn-linked carbohydrate chain of about 2000 Da
proteolytic modification
-
zymogen: pepsinogen C
proteolytic modification
-
zymogen: progastricsin
proteolytic modification
-
the zymogen pepsinogen C is activated after secretion
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure determination
-
molecular structure and comparison with that of porcine pepsinogen
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the pepsin C activity decreases due to its autocatalytical activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
pepsinogen C1- and C-2
-
native zymogen from stomach, prostate, breast cysts fluid, and seminal plasma, native mature enzyme from gastric fluid by anion exchange chromatography
-
rapid single-step separation of pepsin from gastricsin from crude human gastric juice and prepurified gastric mucosa extract
-
native zymogen
-
pepsinogen C-1 and C-2
-
native enzyme from stomach
-
native zymogen
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
location on chromosome 6
-
DNA sequence determination
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the decrease of progastricsin expression indicates dedifferentiation or malignancy of cancer cells
P20142
progasticsin gene expression is up-regulated following gastrin, secretin, and forskolin stimulation of adenylate cyclase activity
P20142
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies
medicine
P20142
the tissue expression of progatricsin represents a powerful tool for the diagnosis of prostate cancer. The enzyme is also a biomarker for gastric carcinoma and plays a direct role in the development of breast tumor progression