Peptidase M1, membrane alanine aminopeptidase
IPR014782
Definition
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 ([ec:3.4.11.2]) is part of the HEXXH+E group; it consists entirely of aminopeptidases, spread across a wide variety of species PMID:7674922. Functional studies show that CD13/APN catalyses 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-A4 to form an inflammatory mediator PMID:7674922. This hydrolase has been shown to have aminopeptidase activity PMID:2244921, and the zinc ligands of the M1 family were identified by site-directed mutagenesis on this enzyme PMID:7674922 CD13 participates in trimming peptides bound to MHC class II molecules PMID:8691132 and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils PMID:8627182. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratory tract infections. Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site PMID:7674922. The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases PMID:7674922.
13 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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