Carboxypeptidase E

From Wikipedia, the free encyclopedia


Carboxypeptidase E
Identifiers
Symbol(s) CPE;
External IDs OMIM: 114855 MGI: 101932 HomoloGene: 48052
EC number 3.4.17.10
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 1363 12876
Ensembl ENSG00000109472 n/a
Uniprot P16870 n/a
Refseq NM_001873 (mRNA)
NP_001864 (protein)		 XM_976304 (mRNA)
XP_981398 (protein)
Location Chr 4: 166.52 - 166.64 Mb n/a
Pubmed search [1] [2]

Carboxypeptidase E, also known as CPE, is a human gene.[1]

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.[1]


Carboxypeptidase E (also called: carboxypeptidase H, enkephalin convertase) is found in neuroendocrine cells and in adrenal gland chromaffin cells. The glycoprotein can be both membrane-associated or soluble. At the C-end of the molecule lies an amphiphilic α-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 exopeptidase to 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 pituitary and 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 endocrine disorders like obesity and infertility. In some strains of mice, the fat mutation also causes hyperproinsulinemia in 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.

[edit] References

  1. ^ a b Entrez Gene: CPE carboxypeptidase E.

[edit] Further reading

  • Goodge KA, Hutton JC (2000). "Translational regulation of proinsulin biosynthesis and proinsulin conversion in the pancreatic beta-cell.". Semin. Cell Dev. Biol. 11 (4): 235–42. doi:10.1006/scdb.2000.0172. PMID 10966857. 
  • Beinfeld MC (2003). "Biosynthesis and processing of pro CCK: recent progress and future challenges.". Life Sci. 72 (7): 747–57. PMID 12479974. 
  • Manser E, Fernandez D, Loo L, et al. (1990). "Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro.". Biochem. J. 267 (2): 517–25. PMID 2334405. 
  • Fricker LD, Snyder SH (1982). "Enkephalin convertase: purification and characterization of a specific enkephalin-synthesizing carboxypeptidase localized to adrenal chromaffin granules.". Proc. Natl. Acad. Sci. U.S.A. 79 (12): 3886–90. PMID 6808517. 
  • O'Rahilly S, Gray H, Humphreys PJ, et al. (1995). "Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function.". N. Engl. J. Med. 333 (21): 1386–90. PMID 7477119. 
  • Naggert JK, Fricker LD, Varlamov O, et al. (1995). "Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity.". Nat. Genet. 10 (2): 135–42. doi:10.1038/ng0695-135. PMID 7663508. 
  • Song L, Fricker L (1995). "Processing of procarboxypeptidase E into carboxypeptidase E occurs in secretory vesicles.". J. Neurochem. 65 (1): 444–53. PMID 7790890. 
  • Hall C, Manser E, Spurr NK, Lim L (1993). "Assignment of the human carboxypeptidase E (CPE) gene to chromosome 4.". Genomics 15 (2): 461–3. doi:10.1006/geno.1993.1093. PMID 8449522. 
  • Guest PC, Arden SD, Rutherford NG, Hutton JC (1996). "The post-translational processing and intracellular sorting of carboxypeptidase H in the islets of Langerhans.". Mol. Cell. Endocrinol. 113 (1): 99–108. PMID 8674818. 
  • Rovere C, Viale A, Nahon J, Kitabgi P (1996). "Impaired processing of brain proneurotensin and promelanin-concentrating hormone in obese fat/fat mice.". Endocrinology 137 (7): 2954–8. PMID 8770919. 
  • Alcalde L, Tonacchera M, Costagliola S, et al. (1996). "Cloning of candidate autoantigen carboxypeptidase H from a human islet library: sequence identity with human brain CPH.". J. Autoimmun. 9 (4): 525–8. doi:10.1006/jaut.1996.0070. PMID 8864828. 
  • Cool DR, Normant E, Shen F, et al. (1997). "Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice.". Cell 88 (1): 73–83. PMID 9019408. 
  • Maeda K, Okubo K, Shimomura I, et al. (1997). "Analysis of an expression profile of genes in the human adipose tissue.". Gene 190 (2): 227–35. PMID 9197538. 
  • Cain BM, Wang W, Beinfeld MC (1997). "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.". Endocrinology 138 (9): 4034–7. PMID 9275097. 
  • Lacourse KA, Friis-Hansen L, Rehfeld JF, Samuelson LC (1997). "Disturbed progastrin processing in carboxypeptidase E-deficient fat mice.". FEBS Lett. 416 (1): 45–50. PMID 9369230. 
  • Utsunomiya N, Ohagi S, Sanke T, et al. (1998). "Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity.". Diabetologia 41 (6): 701–5. PMID 9662053. 
  • Reznik SE, Salafia CM, Lage JM, Fricker LD (1999). "Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord.". J. Histochem. Cytochem. 46 (12): 1359–68. PMID 9815277. 
  • Fan X, Olson SJ, Johnson MD (2001). "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.". J. Histochem. Cytochem. 49 (6): 783–90. PMID 11373325. 
  • Friis-Hansen L, Lacourse KA, Samuelson LC, Holst JJ (2001). "Attenuated processing of proglucagon and glucagon-like peptide-1 in carboxypeptidase E-deficient mice.". J. Endocrinol. 169 (3): 595–602. PMID 11375130. 

[edit] External links

v • d • e
Hydrolase: proteases (EC 3.4)
Exopeptidase 3.4.11-19
Endopeptidase 3.4.21-24
Cathepsin 3.4.18,21,22,23
A - B - C - D - E - F - G - H - K - L1/L2 - S - W - Z