Family M64


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M64

Family type peptidaseM64.001 - IgA peptidase (Clostridium ramosum-type) (Clostridium ramosum), MEROPS Accession MER0016067 (peptidase unit: 347-627)
Content of familyPeptidase family M64 contains a highly selective metalloendopeptidase.
History Identifier created: MEROPS 6.0 (30 August 2002)
Peptidase families S6 and M26 contain immunoglobulin A1-specific endopeptidases that cleave prolyl bonds within the O-glycosylated, tandemly duplicated octapeptide, Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser, in the hinge region of human IgA1. A 13-residue deletion in this region in human IgA2 allotypes A2m(1) and A2m(2) renders them resistant to cleavage by all these IgA1 peptidases, but the IgA endopeptidase in family M64 is able to cleave IgA2 A2m(1).
Catalytic typeMetallo
Active site residuesH539 E540 H543 D550 
Active siteThe active site residues of the IgA endopeptidase from Clostridium ramosum (M64.001) are located in a motif HEFGHGLLGLGDEY (Kosowska et al., 2002). In the distantly-related homologue from Streptomyces coelicolor the glycine is displaced one residue towards the N-terminus. There is no conserved methionine C-terminal to the zinc-binding site in the peptidases of the family (see the Alignment), so they are not typical members of subclan MA(M).
Activities and specificitiesThe C. ramosum IgA peptidase cleaves both the alpha1 and alpha2 A2m(1) heavy chains at the Val-Pro-Cys-Pro221Val222 peptide bond located just before the hinge region (Fujiyama et al., 1986; Kobayashi et al., 1987). In the IgA2 A2m(2) allotype the critical proline residue is replaced by arginine, making this allotype resistant to cleavage. The C. ramosum IgA peptidase is highly specific, and cleavage of no other protein has been detected (Kosowska et al., 2002).
InhibitorsThe enzyme was neither inhibited by, nor cleaved, alpha2-macroglobulin (Potempa & Poulsen.2004), which places it in a small minority of endopeptidases.
Molecular structureThe IgA endopeptidase of C. ramosum is a large mosaic protein of 1235 residues, with an N-terminal signal peptide and a large C-terminal domain that contains a typical gram-positive cell wall anchor motif. The distantly-related homolog in S. coelicolor is a smaller protein with an unrelated C-terminal domain. MEROPS is not able to define the peptidase unit with confidence.
Basis of clan assignmentPredicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi -  
Plants details  
Animals -  
Viruses -  
Biological functionsThe activity of the enzyme in degrading IgA may help the organism to exist as a commensal organism in the human intestine.
Statistics for family M64Sequences:106
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
IgA peptidase (Clostridium ramosum-type)M64.001-
family M64 unassigned peptidasesunassignedYes