Family M18


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family M18

Family type peptidaseM18.001 - aminopeptidase I (Saccharomyces cerevisiae), MEROPS Accession MER0001255 (peptidase unit: 46-514)
Content of familyPeptidase family M18 contains metalloaminopeptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
Family M18 is widely distributed in bacteria and eukaryotes, but only two peptidases in the family have yet been characterised in any detail: yeast aminopeptidase I (M18.001) and mammalian aspartyl aminopeptidase (M18.002).
Catalytic typeMetallo
Active site residuesH132 D134 D303 E339 E340 D385 H479 
Active siteActive site residues have not been identified with certainty, but for aspartyl aminopeptidase (M18.002), mutation of three His residues abolished enzymatic activity (Wilk et al., 2002). The first and third of these residues correspond with the first (H132) and last (H479) of the seven active site residues proposed for the family by MEROPS (see above). The other residues proposed by MEROPS (D134, D303, E339, E340, D385, H479) are well conserved in the alignment for the family, and agree with those in the families of clan MH (M20, M28, M42).
Activities and specificitiesYeast aminopeptidase I is active only in its dodecameric form (see below). It has broad substrate specificity, acting on N-terminal leucine and most other amino acids, but acts only slowly on LeuNHPhNO2 (Metz & Rohm, 1976). In contrast, the mammalian aspartyl aminopeptidase is highly selective for hydrolysis of N-terminal Asp or Glu residues from peptides, and does not accept the arylamide leaving groups that are used in test substrates for many other aminopeptidases (Wilk et al., 1998). A coupled assay with AspAla-Pro-NHNap was used in which dipeptidyl-peptidase IV (S09.003) completed the liberation of the detectable 2-naphthylamine.
Molecular structureThe mature yeast aminopeptidase I is a non-disulfide-linked dodecamer, in which each monomer contains two zinc ions (Metz & Rohm, 1976; Metz et al., 1977). It is notable that the bacterial aminopeptidase, M42.003, also in clan MH, similarly exists as a homo-dodecameric complex (Russo & Baumann, 2004). .
Basis of clan assignmentFor members of this family and family M28 predicted metal ligands occur in the same order in the sequence: H, D, E, D/E, H; and active site residues in the motifs HXD and EE
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsThe precursor of yeast aminopepeptidase I is synthesized without a signal peptide. As described by Andrei-Selmer et al. (2001), the cytosolic protein dodecamerizes and is enclosed in a double-membrane vesicle, which is transported to and fuses with the vacuole. The precursor sequence of aminopeptidase I is removed, probably by cerevisin (S08.052). The mammalian aspartyl aminopeptidase is a cytosolic enzyme, and probably contributes to the catabolism of peptides including those produced by the proteasome. It might well contribute to the N-terminal "trimming" of peptides that are destined for the MHC class I system.
Statistics for family M18Sequences:3103
Identifiers with PDB entries:4
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR001948
PFAM PF02127
Peptidases and Homologues MEROPS ID Structure
aminopeptidase IM18.001Yes
aspartyl aminopeptidaseM18.002Yes
aspartyl aminopeptidase (Plasmodium-type)M18.003Yes
apeA putative peptidaseM18.004Yes
At5g60160 (Arabidopsis thaliana)-like peptidaseM18.A01-
At5g04710 (Arabidopsis thaliana)M18.A02-
family M18 non-peptidase homologuesnon-peptidase homologue-
family M18 unassigned peptidasesunassigned-