- Carboxypeptidase E
Carboxypeptidase E, also known as CPE, is a human
gene.cite web | title = Entrez Gene: CPE carboxypeptidase E| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1363| accessdate = ]
summary_text = Carboxypeptidase E cleaves C-terminal amino acid residues and is involved in neuropeptide processing. It is a peripheral membrane protein. CPE specifically binds regulated secretory pathway proteins, including prohormones, but not constitutively secreted proteins.cite web | title = Entrez Gene: CPE carboxypeptidase E| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1363| accessdate = ]
Carboxypeptidase E (also called: carboxypeptidase H, enkephalin convertase) is found in
neuroendocrinecells and in adrenal gland chromaffin cells. The glycoproteincan be both membrane-associated or soluble. At the C-end of the molecule lies an amphiphilicα-helix which might be responsible for the membrane localisation. Carboxypeptidase E is found in all species of vertebrates that have been examined, and is also present in many other organisms that have been studied (nematode, sea slug). Interesting, carboxypeptidase E is not found in the fruit fly, and another enzyme (presumably carboxypeptidase D) fills in for carboxypeptidase E in this organism.
Carboxypeptidase E appears to have several functions. The active form of carboxypeptidase E was shown to be in secretory vesicles, where it acts as an
exopeptidaseto activate neuropeptides. It does that by cleaving off basic C-terminal amino acids, producing the active form of the peptide. Products of carboxypeptidase E include insulin, enkephalin, and most other neuroendocrine peptides.
It has also been proposed that membrane-associated carboxypeptidase E acts as a sorting signal for regulated secretory proteins in the trans-Golgi network of the
pituitaryand in secretory granules; regulated secretory proteins are mostly hormones and neuropeptides. However, this role for carboxypeptidase E remains controversial, and some evidence shows that this enzyme is not necessary for the sorting of regulated secretory proteins.
Mice with mutant carboxypeptidase E, Cpefat, display
endocrinedisorders like obesityand infertility. In some strains of mice, the fat mutation also causes hyperproinsulinemiain adult male mice, but this is not found in all strains of mice. The obesity and infertility in the Cpefat mice develop with age; young mice (<8 weeks of age) are fertile and have normal body weight. Peptide processing in Cpefat mice is impaired, with a large accumulation of peptides with C-terminal lysine and/or arginine extensions. Levels of the mature forms of peptides are generally reduced in these mice, but not completely eliminated. It is thought that a related enzyme (carboxypeptidase D) also contributes to neuropeptide processing and gives rise to the mature peptides in the Cpefat mice.
*cite journal | author=Goodge KA, Hutton JC |title=Translational regulation of proinsulin biosynthesis and proinsulin conversion in the pancreatic beta-cell. |journal=Semin. Cell Dev. Biol. |volume=11 |issue= 4 |pages= 235–42 |year= 2000 |pmid= 10966857 |doi= 10.1006/scdb.2000.0172
*cite journal | author=Beinfeld MC |title=Biosynthesis and processing of pro CCK: recent progress and future challenges. |journal=Life Sci. |volume=72 |issue= 7 |pages= 747–57 |year= 2003 |pmid= 12479974 |doi=
*cite journal | author=Manser E, Fernandez D, Loo L, "et al." |title=Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro. |journal=Biochem. J. |volume=267 |issue= 2 |pages= 517–25 |year= 1990 |pmid= 2334405 |doi=
*cite journal | author=Fricker LD, Snyder SH |title=Enkephalin convertase: purification and characterization of a specific enkephalin-synthesizing carboxypeptidase localized to adrenal chromaffin granules. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=79 |issue= 12 |pages= 3886–90 |year= 1982 |pmid= 6808517 |doi=
*cite journal | author=O'Rahilly S, Gray H, Humphreys PJ, "et al." |title=Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. |journal=N. Engl. J. Med. |volume=333 |issue= 21 |pages= 1386–90 |year= 1995 |pmid= 7477119 |doi=
*cite journal | author=Naggert JK, Fricker LD, Varlamov O, "et al." |title=Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. |journal=Nat. Genet. |volume=10 |issue= 2 |pages= 135–42 |year= 1995 |pmid= 7663508 |doi= 10.1038/ng0695-135
*cite journal | author=Song L, Fricker L |title=Processing of procarboxypeptidase E into carboxypeptidase E occurs in secretory vesicles. |journal=J. Neurochem. |volume=65 |issue= 1 |pages= 444–53 |year= 1995 |pmid= 7790890 |doi=
*cite journal | author=Hall C, Manser E, Spurr NK, Lim L |title=Assignment of the human carboxypeptidase E (CPE) gene to chromosome 4. |journal=Genomics |volume=15 |issue= 2 |pages= 461–3 |year= 1993 |pmid= 8449522 |doi= 10.1006/geno.1993.1093
*cite journal | author=Guest PC, Arden SD, Rutherford NG, Hutton JC |title=The post-translational processing and intracellular sorting of carboxypeptidase H in the islets of Langerhans. |journal=Mol. Cell. Endocrinol. |volume=113 |issue= 1 |pages= 99–108 |year= 1996 |pmid= 8674818 |doi=
*cite journal | author=Rovere C, Viale A, Nahon J, Kitabgi P |title=Impaired processing of brain proneurotensin and promelanin-concentrating hormone in obese fat/fat mice. |journal=Endocrinology |volume=137 |issue= 7 |pages= 2954–8 |year= 1996 |pmid= 8770919 |doi=
*cite journal | author=Alcalde L, Tonacchera M, Costagliola S, "et al." |title=Cloning of candidate autoantigen carboxypeptidase H from a human islet library: sequence identity with human brain CPH. |journal=J. Autoimmun. |volume=9 |issue= 4 |pages= 525–8 |year= 1996 |pmid= 8864828 |doi= 10.1006/jaut.1996.0070
*cite journal | author=Cool DR, Normant E, Shen F, "et al." |title=Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. |journal=Cell |volume=88 |issue= 1 |pages= 73–83 |year= 1997 |pmid= 9019408 |doi=
*cite journal | author=Maeda K, Okubo K, Shimomura I, "et al." |title=Analysis of an expression profile of genes in the human adipose tissue. |journal=Gene |volume=190 |issue= 2 |pages= 227–35 |year= 1997 |pmid= 9197538 |doi=
*cite journal | author=Cain BM, Wang W, Beinfeld MC |title=Cholecystokinin (CCK) levels are greatly reduced in the brains but not the duodenums of Cpe(fat)/Cpe(fat) mice: a regional difference in the involvement of carboxypeptidase E (Cpe) in pro-CCK processing. |journal=Endocrinology |volume=138 |issue= 9 |pages= 4034–7 |year= 1997 |pmid= 9275097 |doi=
*cite journal | author=Lacourse KA, Friis-Hansen L, Rehfeld JF, Samuelson LC |title=Disturbed progastrin processing in carboxypeptidase E-deficient fat mice. |journal=FEBS Lett. |volume=416 |issue= 1 |pages= 45–50 |year= 1997 |pmid= 9369230 |doi=
*cite journal | author=Utsunomiya N, Ohagi S, Sanke T, "et al." |title=Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity. |journal=Diabetologia |volume=41 |issue= 6 |pages= 701–5 |year= 1998 |pmid= 9662053 |doi=
*cite journal | author=Reznik SE, Salafia CM, Lage JM, Fricker LD |title=Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord. |journal=J. Histochem. Cytochem. |volume=46 |issue= 12 |pages= 1359–68 |year= 1999 |pmid= 9815277 |doi=
*cite journal | author=Fan X, Olson SJ, Johnson MD |title=Immunohistochemical localization and comparison of carboxypeptidases D, E, and Z, alpha-MSH, ACTH, and MIB-1 between human anterior and corticotroph cell "basophil invasion" of the posterior pituitary. |journal=J. Histochem. Cytochem. |volume=49 |issue= 6 |pages= 783–90 |year= 2001 |pmid= 11373325 |doi=
*cite journal | author=Friis-Hansen L, Lacourse KA, Samuelson LC, Holst JJ |title=Attenuated processing of proglucagon and glucagon-like peptide-1 in carboxypeptidase E-deficient mice. |journal=J. Endocrinol. |volume=169 |issue= 3 |pages= 595–602 |year= 2001 |pmid= 11375130 |doi=
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