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evolution
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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
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cpe -/- mice is used as a model of EEC dysfunction. Using this model it is shown that CPE exhibits a relevant for EEC function and intestinal homeostasis
malfunction
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in Neuro 2a cells that lack CPE, PC1/3 and PC2, proglucagon co-localise with the Golgi marker p115 as determined by quantitative immunofluorescence microscopy. siRNA-mediated knockdown of CPE disrupts regulated secretion of glucagon from pancreatic-derived alphaTC1-6 cells, but not of GLP-1 from intestinal cell-derived GLUTag cells
malfunction
in two types of carboxypeptidase E mutant mice, Cpefat/Cpefat and Cpe knockout, loss of normal carboxypeptidase E leads to a lot of disorders, including diabetes, hyperproinsulinemia, low bone mineral density and deficits in learning and memory
malfunction
in two types of carboxypeptidase E mutant mice, Cpefat/Cpefat and Cpe knockout, loss of normal carboxypeptidase E leads to a lot of disorders, including diabetes, hyperproinsulinemia, low bone mineral density and deficits in learning and memory
physiological function
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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
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carboxypeptidase E mediates the effects of nitric oxide synthase 1 adaptor protein on dendrite morphology
physiological function
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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
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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
physiological function
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
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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
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
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CPE acts extracellularly through activation of ERK and AKT signaling pathways to up-regulate expression of the anti-apoptotic protein BCL-2 to mediate neuroprotection of neurons during stress
physiological function
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CPE can mediate neuroprotection of the hippocampal neurons during mild chronic restraint stress and may play an important role in maintaining allostasis
physiological function
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CPE exhibits antibacterial activity in human semen
physiological function
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CPE-DELTA neuroprotects neurons against glutamate neuroexcitotoxicity and H2O2-induced oxidative stress.CPE-DELTAN acts by increasing the transcription and secretion of fibroblast growth factor (FGF2)
physiological function
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sorting of proglucagon to secretory granules is mediated by carboxypeptidase E
physiological function
overexpression of the secreted form of CPE is accompanied by differential regulation of mRNAs connected to the motility-associated networks, among others adhesion kinase FAK, p21-activated kinase PAK, cell division cycle 42 (Cdc42), integrin, STAT3 as well as TGF-beta. Especially SLUG is downregulated in sCPE-overexpressing glioma cells, paralleled by reduced expression of matrix-metalloproteinases (MMP) and, in consequence, by decreased cell migration. Expression of SLUG is regulated by ERK since inhibition of ERK reverted sCPE-mediated SLUG downregulation and enhanced cell motility. In a mouse glioma model, overexpression of the sectreted form of CPE significantly prolonges survival
physiological function
the enzyme cleaves C-terminal basic amino acids from prohormone intermediates to produce mature peptide hormones and neuropeptides in the endocrine and central nervous systems. It also plays a critical role in prohormone sorting and secretory vesicle transportation. The enzyme exerts multiple non-enzymatic physiological roles in maintaining normal central nervous system function and in neurodevelopment. This includes potent neuroprotective and anti-depressant activities, as well as stem cell differentiation functions. In addition, N-terminal truncated variants of the enzyme regulate expression of important neurodevelopmental genes
physiological function
the enzyme cleaves C-terminal basic amino acids from prohormone intermediates to produce mature peptide hormones and neuropeptides in the endocrine and central nervous systems. It also plays a critical role in prohormone sorting and secretory vesicle transportation. The enzyme exerts multiple non-enzymatic physiological roles in maintaining normal central nervous system function and in neurodevelopment. This includes potent neuroprotective and anti-depressant activities, as well as stem cell differentiation functions. In addition, N-terminal truncated variants of the enzyme regulate expression of important neurodevelopmental genes
physiological function
the enzyme is involved in proneuropeptide processing. It is also a neurotrophic factor (NF-a1) and has important roles in neuroprotection, stem cell differentiation, and neurite outgrowth, independent of enzymatic activity
physiological function
the enzyme is involved in the biosynthesis of a wide range of neuropeptides and peptide hormones in endocrine tissues, and in the nervous system. Membrane carboxypeptidase E mediates the targeting of prohormones to the regulated secretory pathway, while soluble carboxypeptidase E acts as an exopeptidase and cleaves C-terminal basic residues from peptide intermediates to generate bioactive peptides. Carboxypeptidase E also participates in protein internalization, vesicle transport and regulation of signaling pathways
physiological function
the enzyme is involved in the biosynthesis of a wide range of neuropeptides and peptide hormones in endocrine tissues, and in the nervous system. Membrane carboxypeptidase E mediates the targeting of prohormones to the regulated secretory pathway, while soluble carboxypeptidase E acts as an exopeptidase and cleaves C-terminal basic residues from peptide intermediates to generate bioactive peptides. Carboxypeptidase E also participates in protein internalization, vesicle transport and regulation of signaling pathways
physiological function
the enzyme plays a critical role in prohormone sorting and secretory vesicle transportation
physiological function
the enzyme plays a critical role in prohormone sorting and secretory vesicle transportation
physiological function
the enzyme plays a key role in sorting prohormones, such as pro-opiomelanocortin, to regulated secretory vesicles. Human growth hormone directly interacts with carboxypeptidase E