Carboxypeptidase E

Source: Wikipedia, the free encyclopedia.
CPE
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000109472

ENSMUSG00000037852

UniProt

P16870

Q00493

RefSeq (mRNA)

NM_001873

NM_013494

RefSeq (protein)

NP_001864

NP_038522

Location (UCSC)Chr 4: 165.36 – 165.5 MbChr 8: 65.05 – 65.15 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Carboxypeptidase E (CPE), also known as carboxypeptidase H (CPH) and enkephalin convertase, is an

polypeptides
.

CPE is involved in the biosynthesis of most neuropeptides and peptide hormones.[6] The production of neuropeptides and peptide hormones typically requires two sets of enzymes that cleave the peptide precursors, which are small proteins. First, proprotein convertases cut the precursor at specific sites to generate intermediates containing C-terminal basic residues (lysine and/or arginine). These intermediates are then cleaved by CPE to remove the basic residues. For some peptides, additional processing steps, such as C-terminal amidation, are subsequently required to generate the bioactive peptide, although for many peptides the action of the proprotein convertases and CPE is sufficient to produce the bioactive peptide.[7]

Tissue distribution

Carboxypeptidase E is found in brain and throughout the neuroendocrine system, including the

amphiphilic
α-helix within the C-terminal region of the protein.

Species distribution

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). Carboxypeptidase E is not found in the fruit fly (Drosophila), and another enzyme (presumably carboxypeptidase D) fills in for carboxypeptidase E in this organism. In humans, CPE is encoded by the CPE gene.[5][8]

Function

Carboxypeptidase E
Identifiers
ExPASy
NiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Carboxypeptidase E functions in the production of nearly all neuropeptides and peptide hormones. The enzyme 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, the enkephalins, vasopressin, oxytocin, and most other neuroendocrine peptide hormones and neuropeptides.

It has been proposed that membrane-associated carboxypeptidase E acts as a

pituitary and in secretory granules; regulated secretory proteins are mostly hormones and neuropeptides.[9]
However, this role for carboxypeptidase E remains controversial, and evidence shows that this enzyme is not necessary for the sorting of regulated secretory proteins.

Clinical significance

Mice with mutant carboxypeptidase E, Cpefat, display

endocrine disorders like obesity and infertility.[10] 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 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.

Mutations in the CPE gene are not common within the human population, but have been identified. One patient with extreme obesity (Body Mass Index >50) was found to have a mutation that deleted nearly the entire CPE gene.[11] This patient had intellectual disability (inability to read or write) and had abnormal glucose homeostasis, similar to mice lacking CPE activity.

In obesity, high levels of circulating free fatty acids have been reported to cause a decrease in the amount of carboxypeptidase E protein in pancreatic

ER stress).[12]
However, because CPE is not a rate-limiting enzyme for the production of most neuropeptides and peptide hormones, it is not clear how relatively modest decreases in CPE activity can cause physiological effects.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109472 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037852 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: CPE carboxypeptidase E".
  6. PMID 2897826
    .
  7. ISBN 978-1-61504-521-1. {{cite book}}: |journal= ignored (help
    )
  8. PMID 2334405
    .
  9. S2CID 18629145
    .
  10. S2CID 19798125
    .
  11. PMID 26120850
    .
  12. PMID 18550819
    .

Further reading

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Carboxypeptidase_E&oldid=1195397704"