Information on EC 3.4.21.2 - chymotrypsin C

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY
3.4.21.2
-
RECOMMENDED NAME
GeneOntology No.
chymotrypsin C
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Preferential cleavage: Leu-/-, Tyr-/-, Phe-/-, Met-/-, Trp-/-, Gln-/-, Asn-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
endopeptidase
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
caldecrin
-
-
caldecrin
-
chymotrypsin C
-
-
chymotrypsinogen C
-
-
elastase-associated acidic endopeptidase
-
-
elastase-like chymotrypsin
-
-
enzyme Y
chymotrypsin C is identical to enzyme Y, the trypsinogen-degrading enzymatic activity isolated from human pancreatic juice
Granzyme M
-
-
GrzM
-
-
Serum calcium-decreasing factor
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9036-09-3
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
pancreatitis-associated CTRC mutations can markedly increase the propensity of chymotrypsinogen C to elicit endoplasmic reticulum stress in pancreatic acinar cells. Diminished secretion and intracellular retention/degradation of the p.A73T CTRC mutant. Endoplasmic reticulum stress in AR42J cells is proportional to intracellular levels of the p.A73T CTRC mutant. No activation of the PERK pathway and NFkappaB in acinar cells expressing the p.A73T CTRC mutant. Apoptotic cell death in AR42J cells expressing the p.A73T CTRC mutant
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
A chain of oxidized insulin + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-L-Leu methyl ester + H2O
acetyl-L-Leu + methanol
show the reaction diagram
-
-
-
?
acetyl-L-Trp ethyl ester + H2O
acetyl-L-Trp + ethanol
show the reaction diagram
-
-
-
-
acetyl-L-Trp ethyl ester + H2O
acetyl-L-Trp + ethanol
show the reaction diagram
-
-
-
?
B chain of oxidized insulin + H2O
?
show the reaction diagram
-
-
-
-
?
benzoyl-L-Leu methyl ester + H2O
benzoyl-L-Leu + methanol
show the reaction diagram
-
-
-
?
benzoyl-L-Met ethyl ester + H2O
benzoyl-L-Met + ethanol
show the reaction diagram
-
-
-
?
benzoyl-L-Tyr ethyl ester + H2O
benzoyl-L-Tyr + ethanol
show the reaction diagram
-
-
-
?
benzoyl-L-Tyr ethyl ester + H2O
benzoyl-L-Tyr + ethanol
show the reaction diagram
-
-
-
?
benzoyl-Leu-ethyl ester + H2O
benzoyl-Leu + ethanol
show the reaction diagram
-
-
-
?
benzoyl-Phe ethyl ester + H2O
benzoyl-Phe + ethanol
show the reaction diagram
-
-
-
-
benzoyl-Phe ethyl ester + H2O
benzoyl-Phe + ethanol
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Leu-Gly-amide + H2O
benzyloxycarbonyl-L-Leu-Gly + NH3
show the reaction diagram
-
-
-
?
carboxymethylated reduced ribonuclease + H2O
?
show the reaction diagram
-
-
-
-
?
cationic trypsin + H2O
?
show the reaction diagram
-
selectively cleaves the Leu81-Glu82 peptide bond within the Ca2-binding loop
-
?
cationic trypsinogen + H2O
?
show the reaction diagram
-
chymotrypsin activates trypsinogen by cleaving the N-terminal tripeptide of the protein
-
-
-
cationic trypsinogen A16V + H2O
?
show the reaction diagram
-
the A16V mutation of trypsinogen is processed 4fold more rapidly compared to wild-type trypsiongen
-
-
-
Glucagon + H2O
?
show the reaction diagram
-
-
-
-
?
N-acetyl-Tyr ethyl ester + H2O
N-acetyl-Tyr + ethanol
show the reaction diagram
-
-
-
?
N-acetyl-Tyr ethyl ester + H2O
N-acetyl-Tyr + ethanol
show the reaction diagram
-
-
-
?
N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide + H2O
N-succinyl-Ala-Ala-Pro-Phe + p-nitroaniline
show the reaction diagram
-
-
-
?
N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide + H2O
N-succinyl-Ala-Ala-Pro-Phe + p-nitroaniline
show the reaction diagram
-
-
?
N-succinyl-L-Ala-Ala-Pro-Leu-p-nitroanilide + H2O
N-succinyl-L-Ala-Ala-Pro-Leu + p-nitroaniline
show the reaction diagram
-
-
-
?
oxidized oxytocin + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl acetate + H2O
p-nitrophenol + acetate
show the reaction diagram
-
-
-
?
Ser-His-Leu-Val-Glu + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Ala-Ala-Pro-Ala 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Ala + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Asn 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Asn + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Gln 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Gln + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Ile 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Ile + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Leu 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Leu + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Met 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Met + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Phe + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Phe + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Trp 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Trp + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Tyr 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Tyr + 4-nitroaniline
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Pro-Val 4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Val + 4-nitroaniline
show the reaction diagram
-
-
-
?
Trypsinogen + H2O
?
show the reaction diagram
-
-
-
?
human cationic trypsinogen + H2O
?
show the reaction diagram
-
-
enzyme cleaves the Leu81-Glu82 peptide bond in the calcium-binding loop. Chymotrypsin C-mediated cleavage is stimulated threefold by mutation E82A and unaffected by mutations E79A and N84A in human cationic trypsinogen. Specific cleavage of the Leu81-Glu82 peptide bond is primarily determined by the enzymes' distinctively high activity on leucyl peptide bonds, with the P1' Glu82, P3' Asn84 and P4' Glu85 residues serving as additional specificity determinants
-
?
additional information
?
-
-
hydrolysis of Tyr, Phe, Met, Trp, Leu, Glu, and Asp
-
-
-
additional information
?
-
-
no activity with N-benzoyl-L-Tyr-p-nitroanilide, L-Leu-p-nitroanilide, and N-benzoyl-L-Arg-p-nitroanilide
-
-
-
additional information
?
-
-
CTRC cleaves after a P1 Leu with at least tenfold higher catalytic efficiency than other enzymes tested
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ca2+
-
increasing the Ca2+ concentration from 0.025 mM to 1 mM progressively inhibits the degradation of cationic trypsin by chymotrypsin C, with essentially complete protection observed at 1 mM Ca2+
DFP
-
-
diphenyl carbamoyl chloride
-
-
tosyl-L-Leu chloromethyl ketone
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
10
acetyl-L-Leu methyl ester
-
-
2.1
acetyl-L-Trp ethyl ester
-
-
13
Acetyl-Tyr ethyl ester
-
-
28
benzoyl-L-Leu ethyl ester
-
-
0.4
benzoyl-L-Leu methyl ester
-
-
10
benzoyl-L-Met ethyl ester
-
-
17
benzoyl-L-Met ethyl ester
-
-
0.85
benzoyl-L-Phe ethyl ester
-
-
2
benzoyl-L-Tyr ethyl ester
-
-
15
benzyloxycarbonyl-L-Leu-Gly-amide
-
-
20
N-Acetyl-Tyr ethyl ester
-
-
0.000168
N-succinyl-L-Ala-Ala-Pro-Leu-p-nitroanilide
-
in 50 mM Tris-HCl (pH 8.0), with 20 mM CaCl2, at 37C
0.392
succinyl-Ala-Ala-Pro-Ala 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
3.452
succinyl-Ala-Ala-Pro-Asn 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.738
succinyl-Ala-Ala-Pro-Gln 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.0605
succinyl-Ala-Ala-Pro-Ile 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.0118
succinyl-Ala-Ala-Pro-Leu 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.0304
succinyl-Ala-Ala-Pro-Met 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.013
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
wild-type, pH 8.0, 22C
0.015
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant R254Q, pH 8.0, 22C; mutant R254W, pH 8.0, 22C
0.016
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant Q48R, pH 8.0, 22C; mutant V235I, pH 8.0, 22C
0.017
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant D35Y, pH 8.0, 22C; mutant G18R, pH 8.0, 22C
0.02
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant R37Q, pH 8.0, 22C
0.022
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
0.024
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant A73T, pH 8.0, 22C
0.482
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant G217S, pH 8.0, 22C
0.495
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant Q178R, pH 8.0, 22C
0.59
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant G32V, pH 8.0, 22C
0.761
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant P249L, pH 8.0, 22C
1.539
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
-
mutant V250E, pH 8.0, 22C
0.0277
succinyl-Ala-Ala-Pro-Trp 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.0196
succinyl-Ala-Ala-Pro-Tyr 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
0.1504
succinyl-Ala-Ala-Pro-Val 4-nitroanilide
-
pH 8.0, temperature not specified in the publication
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
50
acetyl-L-Leu methyl ester
Sus scrofa
-
-
0.32
acetyl-L-Trp ethyl ester
Sus scrofa
-
-
92
Acetyl-Tyr ethyl ester
Sus scrofa
-
-
25.4
benzoyl-L-Leu ethyl ester
Sus scrofa
-
-
28
benzoyl-L-Leu methyl ester
Sus scrofa
-
-
1.7
benzoyl-L-Met ethyl ester
Sus scrofa
-
-
1.55
benzoyl-L-Phe ethyl ester
Sus scrofa
-
-
46
benzoyl-L-Tyr ethyl ester
Sus scrofa
-
-
80
benzoyl-L-Tyr ethyl ester
Sus scrofa
-
-
0.013
benzyloxycarbonyl-L-Leu-Gly amide
Sus scrofa
-
-
170
N-Acetyl-Tyr ethyl ester
Sus scrofa
-
-
0.3
succinyl-Ala-Ala-Pro-Ala 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
3.6
succinyl-Ala-Ala-Pro-Asn 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
1.1
succinyl-Ala-Ala-Pro-Gln 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
0.03
succinyl-Ala-Ala-Pro-Ile 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
9.2
succinyl-Ala-Ala-Pro-Leu 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
14.9
succinyl-Ala-Ala-Pro-Met 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
0.6
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant P249L, pH 8.0, 22C
1.4
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant V250E, pH 8.0, 22C
2.7
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant G217S, pH 8.0, 22C
3.5
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant Q178R, pH 8.0, 22C
10
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant G32V, pH 8.0, 22C
11.7
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant D35Y, pH 8.0, 22C
12.6
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant V235I, pH 8.0, 22C
13.2
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
14.4
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant R37Q, pH 8.0, 22C
15
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
wild-type, pH 8.0, 22C
15.1
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant Q48R, pH 8.0, 22C
15.5
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant R254Q, pH 8.0, 22C
15.7
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant G18R, pH 8.0, 22C
16.6
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant A73T, pH 8.0, 22C; mutant R254W, pH 8.0, 22C
0.1
succinyl-Ala-Ala-Pro-Trp 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
16.6
succinyl-Ala-Ala-Pro-Tyr 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
0.05
succinyl-Ala-Ala-Pro-Val 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.77
succinyl-Ala-Ala-Pro-Ala 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202349
1
succinyl-Ala-Ala-Pro-Asn 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202350
1.5
succinyl-Ala-Ala-Pro-Gln 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202351
0.5
succinyl-Ala-Ala-Pro-Ile 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202352
780
succinyl-Ala-Ala-Pro-Leu 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202353
490
succinyl-Ala-Ala-Pro-Met 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202354
0.79
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant P249L, pH 8.0, 22C
4567
0.91
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant V250E, pH 8.0, 22C
4567
5.5
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant G217S, pH 8.0, 22C
4567
7.1
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant Q178R, pH 8.0, 22C
4567
17
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant G32V, pH 8.0, 22C
4567
600
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
4567
680
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant A73T, pH 8.0, 22C; mutant D35Y, pH 8.0, 22C
4567
710
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant R37Q, pH 8.0, 22C
4567
800
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant V235I, pH 8.0, 22C
4567
920
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant G18R, pH 8.0, 22C
4567
930
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant Q48R, pH 8.0, 22C
4567
1000
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant R254Q, pH 8.0, 22C
4567
1100
succinyl-Ala-Ala-Pro-Phe 4-nitroanilide
Homo sapiens
-
mutant R254W, pH 8.0, 22C; wild-type, pH 8.0, 22C
4567
3.6
succinyl-Ala-Ala-Pro-Trp 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202355
850
succinyl-Ala-Ala-Pro-Tyr 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202356
0.33
succinyl-Ala-Ala-Pro-Val 4-nitroanilide
Homo sapiens
-
pH 8.0, temperature not specified in the publication
202357
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
activity is first detected at 6-7 days of age, glucocorticoids stimulate the perinatal development of pancreatic enzymes
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
72100
-
SDS-PAGE
680126
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 30000, SDS-PAGE
?
-
x * 31800, calculation from amino acid sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
chymotrypsin C is formed from subunit II of procarboxypeptidase A by specific cleavage by trypsin of the first basic bond in the N-terminal region
proteolytic modification
-
zymogen: chymotrypsinogen C
proteolytic modification
-
activation involves the specific cleavage by trypsin of the first basic bond in the N-terminal region
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with small protease inhibitor eglin C, to 1.9 A resolution. The inhibitor binds in a substrate-like manner filling the S6-S5' subsites of the substrate binding cleft. Significant binding affinity derives from burial of preferred hydrophobic residues at the P1, P4, and P2' positions of chymotrypsin C, although acidic P2' residues can also be accommodated by formation of an interfacial salt bridge. There is a ring of intense positive electrostatic surface potential surrounding the primarily hydrophobic substrate binding site. Long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
when activation with enterokinase is carried out further inactivation and/or breakdown occurs
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
aprotinin-agarose column chromatography
-
from inclusion bodies
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNAs for the wild-type CTRC and the p.A73T mutant carrying a Glu-Glu epitope tag excised from pcDNA3.1(-)_CTRC expression plasmids with XhoI and EcoRI and subcloned into the VQ Ad5CMV shuttle vector under the control of a CMV promoter. Dexamethasone-differentiated AR42J rat acinar cells and freshly isolated mouse acini transfected with recombinant adenovirus carrying wild-type CTRC or the p.A73T pancreatitis-associated mutant
-
expressed in HEK293-T cells
-
expression in Escherichia coli Rosetta (DE3)
-
expression in HEK 293T cell
-
expression in HEK-293T cell
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in AR42J cells and mouse acini, CTRC is transiently expressed in its inactive zymogen form
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A73T
-
diminished activity
A73T
-
natural missense variant, 62% of wild-type activity
D35Y
-
natural missense variant, 62% of wild-type activity
G18R
-
natural missense variant, 84% of wild-type activity
G217R
-
natural missense variant, no residual activity
G217S
-
specific activity is about 7% of the wild type enzyme
G217S
-
natural missense variant, 0.5% of wild-type activity
G32V
-
natural missense variant, 1.5% of wild-type activity
mre
-
None of the mutants examined exhibits a gain of function such as increased secretion or activity. 11 mutants show marked loss of function, 3 mutants have moderate functional defects, whereas 18 mutants are functionally similar to wild-type. The functional deficiencies observed are diminished secretion, impaired catalytic activity and degradation by trypsin. Mutants with a secretion defect cause ER stress that is proportional to the loss in secretion. ER stress is not associated with loss-of-function phenotypes related to catalytic defect or proteolytic instability
P249L
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natural missense variant, 0.07% of wild-type activity
Q178R
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natural missense variant, 0.6% of wild-type activity
Q48R
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mutant shows about 30% activity of the wild type enzyme
Q48R
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natural missense variant, 85% of wild-type activity
R254Q
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natural missense variant, 91% of wild-type activity
R254W
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shows about 50% of wild-type activity
R254W
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natural missense variant, 100% of wild-type activity
R37Q
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mutant shows essentially normal activity and secretion (about 82-88% activity of the wild type enzyme)
R37Q
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natural missense variant, 64% of wild-type activity
V235I
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CTRC activity secreted by cells transfected with variant V235I is moderately reduced (about 65% of the wild type enzyme)
V235I
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natural missense variant, 73% of wild-type activity
V250E
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natural missense variant, 0.08% of wild-type activity
K247-R254del
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natural missense variant, no residual activity
additional information
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deletion mutant K247_R254del shows diminished activity
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
carriers of CTRC mutations may be at a higher risk of developing endoplasmic reticulum stress in the exocrine pancreas. Endoplasmic reticulum stress may contribute to parenchymal damage in chronic pancreatitis through acinar cell apoptosis