{PDOC00123} {PS00132; CARBOXYPEPT_ZN_1} {PS00133; CARBOXYPEPT_ZN_2} {BEGIN} *********************************************************** * Zinc carboxypeptidases, zinc-binding regions signatures * *********************************************************** 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. -Consensus pattern: [PK]-x-[LIVMFY]-x-[LIVMFY]-x(2)-{E}-x-H-[STAG]-x-E-x- [LIVM]-[STAG]-{L}-x(5)-[LIVMFYTA] [H and E are zinc ligands] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: Bacillus sphaericus endopeptidase I which hydrolyses the gamma-D-Glu-(L)meso-diaminopimelic acid bond of spore cortex peptidoglycan [6] and which is possibly distantly related to zinc carboxypeptidases. -Consensus pattern: H-[STAG]-{ADNV}-{VGFI}-{YAR}-[LIVME]-{SDEP}-x-[LIVMFYW]-P- [FYW] [H is a zinc ligand] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: 52. -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. [ 1] Tan F., Chan S.J., Steiner D.F., Schilling J.W., Skidgel R.A. "Molecular cloning and sequencing of the cDNA for human membrane-bound carboxypeptidase M. Comparison with carboxypeptidases A, B, H, and N." J. Biol. Chem. 264:13165-13170(1989). PubMed=2753907 [ 2] Reynolds D.S., Stevens R.L., Gurley D.S., Lane W.S., Austen K.F., Serafin W.E. "Isolation and molecular cloning of mast cell carboxypeptidase A. A novel member of the carboxypeptidase gene family." J. Biol. Chem. 264:20094-20099(1989). PubMed=2584208 [ 3] Narahashi Y. "The amino acid sequence of zinc-carboxypeptidase from Streptomyces griseus." J. Biochem. 107:879-886(1990). PubMed=2118139 [ 4] Teplyakov A., Polyakov K., Obmolova G., Strokopytov B., Kuranova I., Osterman A., Grishin N., Smulevitch S., Zagnitko O., Galperina O. "Crystal structure of carboxypeptidase T from Thermoactinomyces vulgaris." Eur. J. Biochem. 208:281-288(1992). PubMed=1521526 [ 5] He G.-P., Muise A., Li A.W., Ro H.-S. "A eukaryotic transcriptional repressor with carboxypeptidase activity." Nature 378:92-96(1995). PubMed=7477299; DOI=10.1038/378092a0 [ 6] Hourdou M.-L., Guinand M., Vacheron M.J., Michel G., Denoroy L., Duez C.M., Englebert S., Joris B., Weber G., Ghuysen J.-M. "Characterization 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." Biochem. J. 292:563-570(1993). PubMed=8503890 [ 7] Rawlings N.D., Barrett A.J. "Evolutionary families of metallopeptidases." Methods Enzymol. 248:183-228(1995). PubMed=7674922 [E1] https://www.uniprot.org/docs/peptidas -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}