Information on EC 3.4.17.10 - carboxypeptidase E

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY hide
3.4.17.10
-
RECOMMENDED NAME
GeneOntology No.
carboxypeptidase E
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
release of C-terminal arginine or lysine residues from polypeptides
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
81876-95-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
tobacco hornworm
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57/BL6 mice
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
the amino acid sequence of carboxypeptidase E appears to be highly conserved among chicken, mouse, and human. The C-terminal sequence of carboxypeptidase E, which serves as an anchor to the membrane of secretory granules, is perfectly conserved between birds and mammals
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Met)enkephalin-Arg + H2O
Tyr-Gly-Gly-Phe-Met + Arg
show the reaction diagram
(Met)enkephalin-Lys + H2O
Tyr-Gly-Gly-Phe-Met + Lys
show the reaction diagram
acetyl-Tyr-Ala-Arg + H2O
acetyl-Tyr-Ala + Arg
show the reaction diagram
benzoyl-Phe-Ala-Arg + H2O
benzoyl-Phe-Ala + Arg
show the reaction diagram
D-Tyr-Ala-His-Lys-Lys + H2O
D-Tyr-Ala-His-Lys + Lys
show the reaction diagram
-
-
-
-
?
Dansyl-Ala-Arg + H2O
Dansyl-Ala + Arg
show the reaction diagram
-
-
-
-
?
dansyl-Gly-Lys + H2O
dansyl-Gly + Lys
show the reaction diagram
-
-
-
-
?
Dansyl-Phe-Ala-Arg + H2O
Dansyl-Phe-Ala + Arg
show the reaction diagram
Dansyl-Phe-Gly-Arg + H2O
Dansyl-Phe-Gly + Arg
show the reaction diagram
-
-
-
-
?
Dansyl-Phe-Ile-Arg + H2O
Dansyl-Phe-Ile + Arg
show the reaction diagram
-
-
-
-
?
dansyl-Phe-Leu-Ala-Arg + H2O
dansyl-Phe-Leu-Ala + Arg
show the reaction diagram
-
-
-
-
?
Dansyl-Phe-Leu-Arg + H2O
Dansyl-Phe-Leu + Arg
show the reaction diagram
dansyl-Phe-Leu-Gly-Arg + H2O
dansyl-Phe-Leu-Gly + Arg
show the reaction diagram
-
-
-
-
?
Dansyl-Pro-Ala-Arg + H2O
Dansyl-Pro-Ala + Arg
show the reaction diagram
-
-
-
-
?
enkephalin precursor + H2O
?
show the reaction diagram
-
-
-
-
?
furylacrylic-Ala-Arg + H2O
furylacrylic-Ala + Arg
show the reaction diagram
-
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
-
?
iodo-acetyl-Tyr-Ala-Arg + H2O
iodo-acetyl-Tyr-Ala + Arg
show the reaction diagram
-
-
-
-
?
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide + pro-islet amyloid polypeptide propeptide
show the reaction diagram
proinsulin tryptic peptides + H2O
?
show the reaction diagram
-
-
-
-
?
[Leu5]enkephalin-Arg6-Arg7 + H2O
[Leu5]enkephalin + Arg
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide + pro-islet amyloid polypeptide propeptide
show the reaction diagram
-
processing in pancreatic beta-cells
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
enhances the binding of CPE to secretogranin III
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
-
4-Chloromercuriphenylsulfonate
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over 95% inhibition at 0.1 mM
Aminopropylmercapto succinic acid
arginine
-
-
Guanidinoethylmercaptosuccinic acid
Leu-enkephalin
Luteinizing hormone-releasing hormone
lysine
-
-
Met-enkephalin
Met-Enkephalin-Arg-Gly-Leu
Met-Enkephalin-Arg6-Phe7
Oxytoxin
p-Chloromercuriphenyl sulfonate
Substance P
sulfhydryl reagents
thyrotropin-releasing hormone
Vasopressin
[Leu5]Enkephalin-Arg6
-
-
[Leu5]Enkephalin-Lys6
-
-
[Met5]Enkephalin-Arg6
-
-
[Met5]Enkephalin-Lys6
-
-
additional information
-
excessive secretogranin III leads to a decrease in CPE-bound proopiomelanocortin-derived intermediate molecules
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
allyl isothiocyanate
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mRNA for carboxypeptidase E is transiently increased in the first 6 h, after which is decreased to below baseline levels, after intracolonically administration of allyl isothiocyanate
additional information
-
tryptic activation of the pancreatic zymogen
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 0.12
Dansyl-Ala-Arg
-
-
0.018 - 0.034
dansyl-Phe-Ala-Arg
0.029 - 0.031
dansyl-Phe-Gly-Arg
-
-
0.068 - 0.077
dansyl-Phe-Ile-Arg
-
-
0.34 - 0.49
dansyl-Phe-Leu-Ala-Arg
-
-
0.0175 - 0.071
dansyl-Phe-Leu-Arg
0.16 - 0.18
dansyl-Phe-Leu-Gly-Arg
-
-
0.058 - 0.062
Dansyl-Pro-Ala-Arg
-
-
0.4
hippuryl-Arg
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-
0.028
iodo-acetyl-Tyr-Ala-Arg
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
13
dansyl-Phe-Ala-Arg
Sus scrofa
-
-
8.5
hippuryl-Arg
Sus scrofa
-
-
16
iodo-acetyl-Tyr-Ala-Arg
Sus scrofa
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120
-
-
additional information
-
metabolic parameters of wild-type, heterozygous and homozygeous enzyme-deficient mutant mice, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 5.5
5 - 6
-
-
5 - 5.5
5.5 - 6.5
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 6.5
-
pH 4: about 20% of activity maximum, pH 6.5: about 15% of activity maximum
5 - 6
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-
5
-
CPE reaction
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.1
-
calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
tissue distribution of CPE
Manually annotated by BRENDA team
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immortalized bronchial epithelial cell line
Manually annotated by BRENDA team
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contitioned culture medium, from hepatoma cells
Manually annotated by BRENDA team
-
transiently expressed in mouse embryos from embryonic day 5.5 to postnatal day 1
Manually annotated by BRENDA team
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specifically expressed in enteroendocrine cell of the murine colon and ileum
Manually annotated by BRENDA team
-
CPE expression occurs in gastrin synthesizing cells and in gastrin-somatostatin progenitor cells
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
present in some dendrites and nerve terminals, which contain storage vesicles
Manually annotated by BRENDA team
-
in decidua and chorionic plate at various stages of gestation
Manually annotated by BRENDA team
-
primary, 17 different biopsies
Manually annotated by BRENDA team
-
carboxypeptidase E is expressed in chicken thymus of both young (8-day-old) and older (17-week-old) chickens and in broilers and laying hens
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
associated with brain-derived neurotrophic factor, BDNF, vesicles
Manually annotated by BRENDA team
-
enkephalin-containing chromaffin vesicles in the adrenal medulla, the enzyme is sorted into the secretory pathway via its C-terminal domain
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000
-
non-denaturing PAGE, gel filtration
52000 - 54000
-
gel filtration
52400
-
calculated
70000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 55000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
-
the 55 kDa proenzyme is processed to the 53 kDa mature protein
side-chain modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, partially purified enzyme, 1 month, 90% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ion exchange, heparin affinity and gel filtration chromatography
-
native enzyme from brain to homogeneity by 4-aminobenzoyl affinity chromatography
-
native enzyme from pituitary to homogeneity from pituitary gland by 4-aminobenzoyl-Arg affinity chromatography with elution at pH 8.0
-
partial
-
partially by isolation of beta-islet cells
-
recombinant GST-fusion protein from Escherichia coli strain BL21(DE3) by glutathione affinity, native pro- or mature enzyme from AtT20 cells, best at pH 5.5 in presence of Ca2+ by GST-secretogranin III affinity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a cDNA library is constructed with polyA+ RNA isolated from the neural complex, EST sequences are determined, cluster ID 00509, longest cDNA clone for Ci-CPE ciad075c14, accession no. AK113574
-
a GST-tagged CPE tail fragment is generated using the pGEX4T-2 vector, furthermore the vectors pEGFP-1C, pDsRed2 and pCMV-Myc are used to generate GFP, RFP and Myc fusion proteins
-
CPE gene and total gene quantitative expression analysis in lung tumor tissue, detailed overview
-
CPE tail fragments are subcloned into pGEX4T-2, pEGFP-C1 and pDsRed2, full-length CPE cDNA is inserted into pDsRed-Express-N1
-
DNA and amino acid sequence determination, localization on chromosome 4, several naturally occurring genetic variants exist
-
DNA and amino acid sequence determination, localization on chromosome 8
-
expression as GST-fusion protein in Escherichia coli strain BL21(DE3)
-
expression in HEK-293 cells
-
expression in Sf9/baculovirus
-
HEK 293 T cells are transiently transfected with dopamine transporter or together with carboxypeptidase E, carboxypeptidase E interacts with the dopamine transporter carboxyl terminus and affects dopamine transporter function. Mammalian cell lines coexpressing carboxypeptidase E and dopamine transporter exhibit increased dopamine transporter-mediated dopamine uptake activity compared to cells expressing dopamine transporter alone. Coexpression of an interfering dopamine transporter carboxyl terminus minigene inhibit the effects of carboxypeptidase E on dopamine transporter. Functional changes caused by carboxypeptidase E could be attributed to enhanced dopamine transporter expression and subsequent increase in dopamine transporter cell surface localization, due to decreased dopamine transporter degradation. Carboxypeptidase E association could reduce the phosphorylation state of dopamine transporter on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal dopamine transporter localization
synthetic construct
-
high level expression in insect cells using the baculovirus transfection system, the recombinant enzyme is indistinguishable from the native enzyme, expression in bacteria results in inactive enzyme
-
interaction of the recombinant enzyme with recombinnat eosinophil cationic protein in the yeast two-hybrid system via residues 318-387 of CPE, overview, expression of the enzyme fused to the activation domain of Gal4 in GH3 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
after mild chronic restraint stress, CPE protein and mRNA are significantly elevated in the hippocampal CA3 region, compared to nave littermate
-
beta cells lacking the insulin receptor show a decreased expression of CPE
-
CPE protein expression is up-regulated by insulin stimulation in beta cells lacking the insulin receptor
-
CPE-DELTAN expression is up-regulated in embryonic hippocampal neurons in response to dexamethasone treatment
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R283W
-
naturally occurring genetic variant of the enzyme, the mutant shows altered kinetics, heat stability, and pH optimum, and a 50% reduced activity compared to the wild-type enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
-
carboxypeptidase E is used in an in vitro system for the production of bioactive peptides
diagnostics
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CPE serves as a marker for pulmonary endocrine tumor cells in the lung, enzyme expression correlates with a good prognosis, while expression of gamma-glutamyl hydrolase is correlated with a poor prognosis, overview
drug development
-
carboxypeptidase E plays a role in the regulation of dopamine transporter trafficking and dopamine transporter-mediated dopamine uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity
medicine