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PROSITE documentation PDOC00123 [for PROSITE entry PS00133]

Zinc carboxypeptidases, zinc-binding regions signatures





Description

There are a number of different types of zinc-dependent carboxypeptidases (EC 3.4.17.-) [1,2]. All these enzymes seem to be structurally and functionally related. The enzymes that belong to this family are listed below.

  • Carboxypeptidase A1 (EC 3.4.17.1), a pancreatic digestive enzyme that can removes all C-terminal amino acids with the exception of Arg, Lys and Pro.
  • Carboxypeptidase A2 (EC 3.4.17.15), a pancreatic digestive enzyme with a specificity similar to that of carboxypeptidase A1, but with a preference for bulkier C-terminal residues.
  • Carboxypeptidase B (EC 3.4.17.2), also a pancreatic digestive enzyme, but that preferentially removes C-terminal Arg and Lys.
  • Carboxypeptidase N (EC 3.4.17.3) (also known as arginine carboxypeptidase), a plasma enzyme which protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation.
  • Carboxypeptidase H (EC 3.4.17.10) (also known as enkephalin convertase or carboxypeptidase E), an enzyme located in secretory granules of pancreatic islets, adrenal gland, pituitary and brain. This enzyme removes residual C- terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing.
  • Carboxypeptidase M (EC 3.4.17.12), a membrane bound Arg and Lys specific enzyme. It is ideally situated to act on peptide hormones at local tissue sites where it could control their activity before or after interaction with specific plasma membrane receptors.
  • Mast cell carboxypeptidase (EC 3.4.17.1), an enzyme with a specificity to carboxypeptidase A, but found in the secretory granules of mast cells.
  • Streptomyces griseus carboxypeptidase (Cpase SG) (EC 3.4.17.-) [3], which combines the specificities of mammalian carboxypeptidases A and B.
  • Thermoactinomyces vulgaris carboxypeptidase T (EC 3.4.17.18) (CPT) [4], which also combines the specificities of carboxypeptidases A and B.
  • AEBP1 [5], a transcriptional repressor active in preadipocytes. AEBP1 seems to regulate transcription by cleavage of other transcriptional proteins.
  • Yeast hypothetical protein YHR132c.

All of these enzymes bind an atom of zinc. Three conserved residues are implicated in the binding of the zinc atom: two histidines and a glutamic acid We have derived two signature patterns which contain these three zinc-ligands.

Note:

If a protein includes both signatures, the probability of it being a eukaryotic zinc carboxypeptidase is 100%

Note:

These proteins belong to families M14A/M14B in the classification of peptidases [7,E1].

Last update:

April 2006 / Pattern revised.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

CARBOXYPEPT_ZN_2, PS00133; Zinc carboxypeptidases, zinc-binding region 2 signature  (PATTERN)

CARBOXYPEPT_ZN_1, PS00132; Zinc carboxypeptidases, zinc-binding region 1 signature  (PATTERN)


References

1AuthorsTan F. Chan S.J. Steiner D.F. Schilling J.W. Skidgel R.A.
TitleMolecular cloning and sequencing of the cDNA for human membrane-bound carboxypeptidase M. Comparison with carboxypeptidases A, B, H, and N.
SourceJ. Biol. Chem. 264:13165-13170(1989).
PubMed ID2753907

2AuthorsReynolds D.S. Stevens R.L. Gurley D.S. Lane W.S. Austen K.F. Serafin W.E.
TitleIsolation and molecular cloning of mast cell carboxypeptidase A. A novel member of the carboxypeptidase gene family.
SourceJ. Biol. Chem. 264:20094-20099(1989).
PubMed ID2584208

3AuthorsNarahashi Y.
TitleThe amino acid sequence of zinc-carboxypeptidase from Streptomyces griseus.
SourceJ. Biochem. 107:879-886(1990).
PubMed ID2118139

4AuthorsTeplyakov A. Polyakov K. Obmolova G. Strokopytov B. Kuranova I. Osterman A. Grishin N. Smulevitch S. Zagnitko O. Galperina O.
TitleCrystal structure of carboxypeptidase T from Thermoactinomyces vulgaris.
SourceEur. J. Biochem. 208:281-288(1992).
PubMed ID1521526

5AuthorsHe G.-P. Muise A. Li A.W. Ro H.-S.
TitleA eukaryotic transcriptional repressor with carboxypeptidase activity.
SourceNature 378:92-96(1995).
PubMed ID7477299
DOI10.1038/378092a0

6AuthorsHourdou M.-L. Guinand M. Vacheron M.J. Michel G. Denoroy L. Duez C.M. Englebert S. Joris B. Weber G. Ghuysen J.-M.
TitleCharacterization of the sporulation-related gamma-D-glutamyl-(L)meso-diaminopimelic-acid-hydrolysing peptidase I of Bacillus sphaericus NCTC 9602 as a member of the metallo(zinc) carboxypeptidase A family. Modular design of the protein.
SourceBiochem. J. 292:563-570(1993).
PubMed ID8503890

7AuthorsRawlings N.D. Barrett A.J.
TitleEvolutionary families of metallopeptidases.
SourceMethods Enzymol. 248:183-228(1995).
PubMed ID7674922

E1Titlehttps://www.uniprot.org/docs/peptidas



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