InterPro domain: IPR001930

This group of metallopeptidases belong to the MEROPS peptidase family M1 (clan MA(E)), the type example being aminopeptidase N from Homo sapiens (Human). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.

Membrane alanine aminopeptidase ( 3.4.11.2 ) is part of the HEXXH ⁺ Egroup; it consists entirely of aminopeptidases, spread across a widevariety of species [ 1 ]. Functional studies show that CD13/APN catalyzes the removal of single amino acids from the amino terminus of small peptides and probably plays a role in their final digestion; one family member (leukotriene-A4 hydrolase) is known to hydrolyse the epoxide leukotriene-A4to form an inflammatory mediator [ 2 ]. This hydrolase has been shown tohave aminopeptidase activity [ 2 ], and the zinc ligands of the M1 familywere identified by site-directed mutagenesis on this enzyme [ 3 ] CD13 participates in trimming peptides bound to MHC class II molecules [ 3 ] and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils [ 4 ]. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratory tract infections.

1. Evolutionary families of metallopeptidases. Meth. Enzymol. 248, 183-228
2. Leukotriene A4 hydrolase: a zinc metalloenzyme. Biochem. Biophys. Res. Commun. 172, 965-70
3. T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides. J. Exp. Med. 184, 183-9
4. Deletion of the NH2-terminal residue converts monocyte chemotactic protein 1 from an activator of basophil mediator release to an eosinophil chemoattractant. J. Exp. Med. 183, 681-5