Information on EC 3.4.17.10 - carboxypeptidase E

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
3.4.17.10
-
RECOMMENDED NAME
GeneOntology No.
carboxypeptidase E
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
release of C-terminal arginine or lysine residues from polypeptides
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
exopeptidase, C-terminus, amino acid
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxypeptidase
-
-
carboxypeptidase E
-
-
-
-
carboxypeptidase E
-
-
carboxypeptidase E
-
-
carboxypeptidase E
-
-
carboxypeptidase E
-
-
carboxypeptidase E
-
-
carboxypeptidase E
P16870
-
carboxypeptidase E
Q00493
-
carboxypeptidase E
-
-
carboxypeptidase E
-
-
carboxypeptidase E/H
-
-
carboxypeptidase H
-
-
carboxypeptidase, enkephalin precursor
-
-
-
-
cobalt stimulated chromaffin granule carboxypeptidase
-
-
-
-
CPE
-
-
-
-
CPE
P16870
-
CPE
Q00493
-
CPH
-
-
-
-
enkephalin convertase
-
-
-
-
enkephalin convertase
-
formerly
enkephalin precursor carboxypeptidase
-
-
-
-
enkephalin-precursor endopeptidase
-
-
-
-
hCPE
-
-
insulin granule-associated carboxypeptidase
-
-
-
-
MCP
-
-
membrane-bound carboxypeptidase
-
-
-
-
peptidyl-L-lysine(-L-arginine) hydrolase
-
-
-
-
Prohormone processing carboxypeptidase
-
-
-
-
metallocarboxypeptidase
-
-
additional information
-
the enzyme belongs to the family of metallocarboxypeptidases
CAS REGISTRY NUMBER
COMMENTARY
81876-95-1
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
physiological function
-
carboxypeptidase E is classically known as an exopeptidase that cleaves carboxy-terminal basic aminoacids from neuropeptide and peptide hormone intermediates resulting in the production of bioactive peptides inneuroendocrine cells. Carboxypeptidase E that is expressed in the nervous and endocrine systems plays multiple non-enzymatic roles in addition to being an exopeptidase The soluble form of carboxypeptidase E acts as a processing enzyme. The membrane-bound form of carboxypeptidase E serves as a sorting receptor for some proneuropeptides and pro-brain derived neurotrophic factor to target them into the regulated secretory pathway.The cytoplasmic tail of the transmembrane form of carboxypeptidase E is shown to be a key molecule in the anchoring of adrenocorticotropic hormone and brain derived neurotrophic factor vesicles to the microtubule-based transport system for post-Golgi delivery of the vesicles to the release site
physiological function
-
glutathione S-transferase pull-down and immunoprecipitation analyses indicate that contactin-associated protein 2 is associated with carboxypeptidase E in vitro and in vivo. Both contactin-associated protein 2 and carboxypeptidase E are expressed predominantly in the CNS. Immunohistochemical analysis reveals that both contactin-associated protein 2- and carboxypeptidase E-like immunoreactivities are found to co-localize in the apical dendrites and cell bodies of rat cortical neurons. In subcellular localization analysis, contactin-associated protein 2- and carboxypeptidase E-like immunoreactivities are co-migrated in the fractions of Golgi/ER. The membrane-bound form of carboxypeptidase E functions as a sorting receptor of prohormones in the trans-Golgi network. Carboxypeptidase E may be a key molecule to regulate contactin-associated protein 2 trafficking to the cell membrane
physiological function
Q00493
glutamatergic and acetylcholine synaptic vesicles in the hypothalamus and chromaffin cell-derived PC12 cells employ the transmembrane carboxypeptidase E cytoplasmic tail to interact with gamma-adducin for recruiting synaptic vesicles to the active and/or pre-active zone to facilitate neurotransmitter release. Carboxypeptidase E is a mediator in the process, that mediates localization of synaptic vesicles to the pre-active zone. Carboxypeptidase E has a non-enzymatic role in the control of classical neurotransmitter release in specific neuron
physiological function
-
carboxypeptidase E plays a role in regulating proper dendritic patterning, especially dendritic pruning and spine formation that are necessary for appropriate synaptogenesis and the establishment of neuronal network
physiological function
-
carboxypeptidase E mediates the effects of nitric oxide synthase 1 adaptor protein on dendrite morphology
physiological function
P16870
the severity of the coronary atherosclerosis estimated by Gensini score is significantly influenced by the presence of the A2925G mutant and G2855A mutant of the carboxypeptidase E gene
physiological function
-
carboxypeptidase E, a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, 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. Moreover, 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. In addition, 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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-Arg + H2O
Tyr-Gly-Gly-Phe-Met + Arg
show the reaction diagram
-
-
-
-
-
(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
-
-
-
-
?
(Met)enkephalin-Lys + H2O
Tyr-Gly-Gly-Phe-Met + Lys
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
-
-
-
-
?
benzoyl-Phe-Ala-Arg + H2O
benzoyl-Phe-Ala + Arg
show the reaction diagram
-
-
-
-
?
benzoyl-Phe-Ala-Arg + H2O
benzoyl-Phe-Ala + Arg
show the reaction diagram
-
-
-
-
?
benzoyl-Phe-Ala-Arg + H2O
benzoyl-Phe-Ala + Arg
show the reaction diagram
-
-
-
-
?
benzoyl-Phe-Ala-Arg + H2O
benzoyl-Phe-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-Ala-Arg + H2O
Dansyl-Phe-Ala + Arg
show the reaction diagram
-
-
-
-
?
Dansyl-Phe-Ala-Arg + H2O
Dansyl-Phe-Ala + Arg
show the reaction diagram
-
-
-
-
?
Dansyl-Phe-Ala-Arg + H2O
Dansyl-Phe-Ala + Arg
show the reaction diagram
-
-
-
-
?
Dansyl-Phe-Ala-Arg + H2O
Dansyl-Phe-Ala + Arg
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-Arg + H2O
Dansyl-Phe-Leu + 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
-
-
-
-
?
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide + pro-islet amyloid polypeptide propeptide
show the reaction diagram
-
processing, processing in pancreatic beta-cells
-
-
?
proinsulin tryptic peptides + H2O
?
show the reaction diagram
-
-
-
-
?
[Leu5]enkephalin-Arg6-Arg7 + H2O
[Leu5]enkephalin + Arg
show the reaction diagram
-
-
-
-
?
iodo-acetyl-Tyr-Ala-Arg + H2O
iodo-acetyl-Tyr-Ala + Arg
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
highly specific for C-terminal basic amino acids in decreasing order: Arg, Lys,His, does not cleave other amino acids
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin
-
-
-
additional information
?
-
-
C-terminal histidine is removed at a very slow rate
-
-
-
additional information
?
-
-
conversion of peptide hormone precursor into their smaller active forms
-
-
-
additional information
?
-
-
conversion of peptide hormone precursor into their smaller active forms
-
-
-
additional information
?
-
-
biosynthesis of insulin in pancreatic beta-cells
-
-
-
additional information
?
-
-
highly specific for C-terminal basic amino acids Arg in decreasing order: Arg, Lys, His, does not cleave other amino acids
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin, associated with the biosynthesis of many peptide neurotransmitters and hormones
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin, associated with the biosynthesis of many peptide neurotransmitters and hormones
-
-
-
additional information
?
-
-
the enzyme is a sorting receptor for the regulated secretory pathway. The sorting receptor function of the enzyme necessitates its interaction with glycosphingolipid-cholesterol rafts at the trans-Golgi network, thereby anchoring it in position to bind to its prohormone cargo
-
?
additional information
?
-
-
the enzyme is a sorting receptor that directs the prohormone pro-opiomelanocortin to the regulated secretory pathway and is also a prohormone processing enzyme in neuro/endocrine cells
-
?
additional information
?
-
-
altered biosynthesis of the neuropeptide processing enzyme after brain ischemia: molecular mechanism and implication
-
-
-
additional information
?
-
-
carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina
-
-
-
additional information
?
-
-
interaction between secretogranin III and carboxypeptidase E facilitates prohormone sorting within secretory granules, both proteins form the separate functional sorting complex by anchoring in the cholesterol-rich membranes of the secretory granules, overview, secretogranin III can funtionally compensate for CPEin enzyme-defective mutant mice
-
-
-
additional information
?
-
-
membrane-bound carboxypeptidase E facilitates the entry of eosinophil cationic protein into neuroendocrine cells
-
-
-
additional information
?
-
-
the enzyme contributes to the sorting of proteins into the secretory pathway
-
-
-
additional information
?
-
-
the enzyme contributes to the sorting of proteins into the secretory pathway, and is involved in the biosynthesis of several peptide hormones and neurotransmitters
-
-
-
additional information
?
-
-
the enzyme binds to secretogranin III
-
-
-
additional information
?
-
-
the enzyme removes C-terminal basic residues, Arg, Lys, and to a minor extent also His, from a variety of substrates, but shows no activity against nonbasic residues, the enzyme prefers Met at the P1 position but tolerates all amino acids, showing low activity in cleaving Pro-Arg bonds, it has a preference for tri- and tetrapeptides compared to dipeptides
-
-
-
additional information
?
-
-
biosynthesis of neuropeptides and peptide hormones
-
-
-
additional information
?
-
-
catalyzes the removal of C-terminal amino acids from proteins and peptides
-
-
-
additional information
?
-
-
FMRFamide-like peptide (FLP) precursors, neuropeptide-like protein (NLP) precursors
-
-
-
additional information
?
-
-
the CPE reaction trims off C-terminal basic residues of peptides
-
-
-
additional information
?
-
-
release of C-terminal arginine or lysine residues from polypeptides
-
-
-
additional information
?
-
-
release of C-terminal arginine or lysine residues from polypeptides
-
-
-
additional information
?
-
-
release of C-terminal arginine or lysine residues from polypeptides
-
-
-
additional information
?
-
-
carboxypeptidase E interacts with the dopamine transporter carboxyl terminus and affects dopamine transporter function, 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
-
-
-
additional information
?
-
-
carboxypeptidase E, a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, 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. Moreover, 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. In addition, 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
-
-
-
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
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide + pro-islet amyloid polypeptide propeptide
show the reaction diagram
-
processing in pancreatic beta-cells
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
C-terminal histidine is removed at a very slow rate
-
-
-
additional information
?
-
-
conversion of peptide hormone precursor into their smaller active forms
-
-
-
additional information
?
-
-
conversion of peptide hormone precursor into their smaller active forms
-
-
-
additional information
?
-
-
biosynthesis of insulin in pancreatic beta-cells
-
-
-
additional information
?
-
-
highly specific for C-terminal basic amino acids Arg in decreasing order: Arg, Lys, His, does not cleave other amino acids
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin, associated with the biosynthesis of many peptide neurotransmitters and hormones
-
-
-
additional information
?
-
-
releases C-terminal arginine or lysine residues from the hexapeptide precursor of [Met]enkephalin and [Leu]enkephalin, forming the pentapeptide enkephalin, associated with the biosynthesis of many peptide neurotransmitters and hormones
-
-
-
additional information
?
-
-
the enzyme is a sorting receptor for the regulated secretory pathway. The sorting receptor function of the enzyme necessitates its interaction with glycosphingolipid-cholesterol rafts at the trans-Golgi network, thereby anchoring it in position to bind to its prohormone cargo
-
?
additional information
?
-
-
the enzyme is a sorting receptor that directs the prohormone pro-opiomelanocortin to the regulated secretory pathway and is also a prohormone processing enzyme in neuro/endocrine cells
-
?
additional information
?
-
-
altered biosynthesis of the neuropeptide processing enzyme after brain ischemia: molecular mechanism and implication
-
-
-
additional information
?
-
-
carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina
-
-
-
additional information
?
-
-
interaction between secretogranin III and carboxypeptidase E facilitates prohormone sorting within secretory granules, both proteins form the separate functional sorting complex by anchoring in the cholesterol-rich membranes of the secretory granules, overview, secretogranin III can funtionally compensate for CPEin enzyme-defective mutant mice
-
-
-
additional information
?
-
-
membrane-bound carboxypeptidase E facilitates the entry of eosinophil cationic protein into neuroendocrine cells
-
-
-
additional information
?
-
-
the enzyme contributes to the sorting of proteins into the secretory pathway
-
-
-
additional information
?
-
-
the enzyme contributes to the sorting of proteins into the secretory pathway, and is involved in the biosynthesis of several peptide hormones and neurotransmitters
-
-
-
additional information
?
-
-
biosynthesis of neuropeptides and peptide hormones
-
-
-
additional information
?
-
-
catalyzes the removal of C-terminal amino acids from proteins and peptides
-
-
-
additional information
?
-
-
FMRFamide-like peptide (FLP) precursors, neuropeptide-like protein (NLP) precursors
-
-
-
additional information
?
-
-
release of C-terminal arginine or lysine residues from polypeptides
-
-
-
additional information
?
-
-
release of C-terminal arginine or lysine residues from polypeptides
-
-
-
additional information
?
-
-
release of C-terminal arginine or lysine residues from polypeptides
-
-
-
additional information
?
-
-
carboxypeptidase E interacts with the dopamine transporter carboxyl terminus and affects dopamine transporter function, 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
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
enhances the binding of CPE to secretogranin III
Co2+
-
stimulates in the millimolar concentration range
Co2+
-
activates
Co2+
-
activates
Co2+
-
activates
Co2+
-
activates
NiCl2
-
stimulates
NiCl2
-
stimulates
Zn2+
-
-
Zn2+
-
metalloenzyme
Co2+
-
activates
additional information
-
metallocarboxypeptidase
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
-
4-Chloromercuriphenylsulfonate
-
over 95% inhibition at 0.1 mM
Aminopropylmercapto succinic acid
-
-
arginine
-
-
Guanidinoethylmercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
HgCl2
-
over 95% inhibition at 0.01 mM
Leu-enkephalin
-
-
Leu-enkephalin
-
-
Luteinizing hormone-releasing hormone
-
-
Met-enkephalin
-
-
Met-enkephalin
-
-
Met-Enkephalin-Arg-Gly-Leu
-
-
p-Chloromercuriphenyl sulfonate
-
-
p-Chloromercuriphenyl sulfonate
-
-
sulfhydryl reagents
-
-
thyrotropin-releasing hormone
-
-
[Leu5]Enkephalin-Arg6
-
-
[Leu5]Enkephalin-Lys6
-
-
[Met5]Enkephalin-Arg6
-
-
[Met5]Enkephalin-Lys6
-
-
Met-Enkephalin-Arg6-Phe7
-
-
additional information
-
excessive secretogranin III leads to a decrease in CPE-bound proopiomelanocortin-derived intermediate molecules
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
allyl isothiocyanate
-
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
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.1
0.12
Dansyl-Ala-Arg
-
-
0.018
-
dansyl-Phe-Ala-Arg
-
pituitary
0.019
-
dansyl-Phe-Ala-Arg
-
adrenal
0.022
-
dansyl-Phe-Ala-Arg
-
brain
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
-
dansyl-Phe-Leu-Arg
-
-
0.027
-
dansyl-Phe-Leu-Arg
-
in presence of CoCl2
0.066
0.071
dansyl-Phe-Leu-Arg
-
-
0.07
-
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
-
-
0.028
-
iodo-acetyl-Tyr-Ala-Arg
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
13
-
dansyl-Phe-Ala-Arg
-
-
8.5
-
hippuryl-Arg
-
-
16
-
iodo-acetyl-Tyr-Ala-Arg
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
120
-
-
-
additional information
-
-
metabolic parameters of wild-type, heterozygous and homozygeous enzyme-deficient mutant mice, overview
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
6
-
-
5.5
-
-
assay at
5.5
-
-
-
5.5
-
-
-
5.6
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
6.5
-
pH 4: about 20% of activity maximum, pH 6.5: about 15% of activity maximum
5
6
-
-
5
-
-
CPE reaction
additional information
-
-
rapid decline in activity at pH values above pH 5.5
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
CPE reaction
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.1
-
-
calculated
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
tissue distribution of CPE
Manually annotated by BRENDA team
-
pituitary corticotrope-derived cells
Manually annotated by BRENDA team
-
immortalized bronchial epithelial cell line
Manually annotated by BRENDA team
-
cortex and striatum
Manually annotated by BRENDA team
-
cortex, striatum, hippocampus
Manually annotated by BRENDA team
-
distal colon
Manually annotated by BRENDA team
-
contitioned culture medium, from hepatoma cells
Manually annotated by BRENDA team
-
neural complex in the endocrine system
Manually annotated by BRENDA team
-
endocrine tissue
Manually annotated by BRENDA team
-
CPE expression occurs in gastrin synthesizing cells and in gastrin-somatostatin progenitor cells
Manually annotated by BRENDA team
-
present in some dendrites and nerve terminals, which contain storage vesicles
Manually annotated by BRENDA team
-
neuroendocrine chromaffin cell, sympathoadrenal chromaffin cell, chromaffin granule
Manually annotated by BRENDA team
-
cortical, culture
Manually annotated by BRENDA team
-
neuronal tissue
Manually annotated by BRENDA team
-
hippocampal and cortical neuron
Manually annotated by BRENDA team
-
pancreatic islets
Manually annotated by BRENDA team
-
neural lobe and intermediate lobe pituitary
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
-
inner, expression analysis
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
-
no expression in mature somatostatin cells and in the majority of serotonin cells
Manually annotated by BRENDA team
additional information
-
gene expression analysis in lung tumor tissue, overview
Manually annotated by BRENDA team
additional information
-
unprocessed pro-enzyme accumulates in cortical neurons after ischemia
Manually annotated by BRENDA team
additional information
-
2 forms: soluble and membrane-bound are present in most tissues
Manually annotated by BRENDA team
additional information
-
-
Manually annotated by BRENDA team
additional information
-
no activity: rat liver, rat spleen, rat lung, rat kidney, rat mammary gland
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
anchored to secretory granules via a C-terminal transmembrane insertion. The membrane-binding domain of the enzyme must adopt an alpha-helical configuration to bind to lipids and the enzyme may require another integral membrane chaperone protein to insert through the lipid bilayer in a transmembrane fashion
Manually annotated by BRENDA team
-
secretory granule membrane derived from trans-Golgi network, associated with detergent-resistant lipid domains, or rafts, within secretory granule membranes
Manually annotated by BRENDA team
-
the enzyme is sorted into the secretory pathway via its C-terminal domain
Manually annotated by BRENDA team
-
membrane-associated via a C-terminal amphipathic sequence
Manually annotated by BRENDA team
-
pH-dependent membrane anchor
Manually annotated by BRENDA team
-
from neural lobe pituitary and intermediate lobe pituitary
Manually annotated by BRENDA team
-
the enzyme binds specifically to cholesterol-rich secretory granule membranes competing with secretogranin III, excessive secretogranin III leads to a decrease in CPE-bound proopiomelanocortin-derived intermediate molecules
Manually annotated by BRENDA team
-
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
-
subcellular localization of wild-type and mutant enzymes in the retina, overview
-
Manually annotated by BRENDA team
additional information
-
co-existence of chromogranin A and carboxypeptidase E in identical neuroendocrine cells in the thymus
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50000
-
-
non-denaturing PAGE, gel filtration
52000
54000
-
gel filtration
52400
-
-
calculated
53000
-
-
soluble protein
53000
-
-
SDS-PAGE
55000
-
-
membrane-associated form
55000
-
-
non-denaturing PAGE
70000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 52000-56000
?
-
x * 53000-59000, different enzyme forms, SDS-PAGE
monomer
-
1 * 55000, SDS-PAGE
additional information
-
structure overview
additional information
-
? * 57000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
glycosylation does not appear to affect the enzyme activity
side-chain modification
-
glycoprotein
glycoprotein
-
glycosylation does not appear to affect the enzyme activity
side-chain modification
-
glycoprotein
side-chain modification
-
glycoprotein
glycoprotein
-
glycosylation does not appear to affect the enzyme activity
glycoprotein
-
alterations in the glycosylation status of the enzyme during ischemia, unprocessed pro-enzyme accumulates in cortical neurons after ischemia
proteolytic modification
-
the 55 kDa proenzyme is processed to the 53 kDa mature protein
side-chain modification
-
glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4°C, partially purified enzyme, 1 month, 90% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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
-
native enzyme from brain to homogeneity by 4-aminobenzoyl affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Sf9/baculovirus
-
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
-
CPE gene and total gene quantitative expression analysis in lung tumor tissue, detailed overview
-
DNA and amino acid sequence determination, localization on chromosome 4, several naturally occurring genetic variants exist
-
expression in HEK-293 cells
-
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
-
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
-
DNA and amino acid sequence determination, localization on chromosome 8
-
expression as GST-fusion protein in Escherichia coli strain BL21(DE3)
-
CPE tail fragments are subcloned into pGEX4T-2, pEGFP-C1 and pDsRed2, full-length CPE cDNA is inserted into pDsRed-Express-N1
-
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
-
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
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
S202P
-
enzyme-defective mutant CPEfat/fat mice show a point mutation in the coding region of the gene encoding the enzyme, and lack enzyme activity completely, which affects peptide processing the mutant mice
S202P
-
inactive mutant, mice without carboxypeptidase E activity are overweight
additional information
-
construction of deletion mutant of CPE
additional information
-
the polymorphisms 801 C to T and 847 C to T are explored
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
-
metabolic analysis of female and male heterozygous and homozygeous enzyme-deficient mutant mice, CPEfat/fat, in comparison to the wild-type mice, the mutant mice show reduced pro-islet amyloid polypeptide processing activity and reduced levels of PC2-chaperone protein 7B2 and prohormone invertase PC2, but not PC1/3, in beta cells, overview
additional information
-
enzyme-defective CPEfat mice show elevated levels of secretogranin III and chromogranin A in the pituitary compensating for the lacking CPE sorting function, overview
additional information
-
a spontaneous Cpefat/fat mutant strain produces an inactive enzyme, which results in diminished cell survival after ischemic stress in the brain in vivo and in neuronal cells in vitro, overview
additional information
-
mutant mice lacking the enzyme and mutant mice with defective enzymes, Cpefat/fat and Cpefat/+ mutants, show abnormal electroretinography responses, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
biotechnology
-
carboxypeptidase E is used in an in vitro system for the production of bioactive peptides
diagnostics
-
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
-
the polymorphism 801 C to T in the carboxypeptidase E exon5 gene may contribiute to the angiographical characteristics of coronary atherosclerosis
medicine
-
enzyme is a potentially important drug target
medicine
-
allyl isothiocyanate induces colon inflammation