Family M3


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


Summary Holotypes Alignment Tree Genomes Literature


Summary Holotypes Alignment Tree Genomes Literature


Summary Holotypes Genomes Literature

Summary for family M3

Family type peptidaseM03.001 - thimet oligopeptidase (Rattus norvegicus), MEROPS Accession MER0001149 (peptidase unit: 2-687)
Content of familyPeptidase family M3 contains metallopeptidases with varied activities.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeMetallo
Active siteLike all peptidases in subclan MA(E), the peptidases in family M3 contain the HEXXH motif that forms the active site in conjunction with a C-terminally-located Glu residue. A single zinc ion is ligated by the sidechains of the two His residues, and the more C-terminal Glu.
Activities and specificitiesVaried peptidase reactions are catalysed by members of family M3. The commonest is a form of endopeptidase activity that is restricted to substrates of low molecule mass, and is therefore termed 'oligopeptidase'. Both thimet oligopeptidase (M03.001) and neurolysin (M03.002) are oligopeptidases, acting only on substrates of less than about 19 amino acid residues, with a particular preference for cleaving near the C-terminus (Knight et al., 1995). The bacterial peptidyl-dipeptidase Dcp (M03.005) liberates C-terminal dipeptides, but the most unusual form of peptidase activity in the family is that of the mitochondrial intermediate peptidase (M03.006) that cleaves N-terminal octapeptides from proteins during their import into mitochondria (Isaya & Kalousek, 1995).
InhibitorsNo protein inhibitors of peptidases in this family have been described. Some oligopeptides are inhibitory, and many potent small-molecule inhibitors have been synthesised (e.g. Vincent et al., 1997 ).
Molecular structureThe peptidases of family M3 are high-molecular-mass (about 80 kDa) zinc metalloendopeptidases. The molecular structure of neurolysin (M03.002) described by Brown et al., (2001) shows that large structural elements prevent the access of substrates to the active site except through a deep narrow channel. This doubtless accounts for the oligopeptidase specificity. The structure of neurolysin shows similarities to those of peptidyl-dipeptidase A peptidase unit 2 (M02.004) and carboxypeptidase Pfu (M32.002) (Natesh et al., 2003), in other families of subclan MA(E).
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of thermolysin, the type example for clan MA.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsMost of the peptidases are synthesised without signal peptides or propeptides, and function intracellularly. Mitochondrial intermediate peptidase is an exception, having a typical mitochondrial leader peptide. One likely function of peptidases in family M3 is the intracellular degradation of oligopeptides. These could include cleaved signal peptides, and products of protein degradation. In vertebrate organisms, some of these peptides might otherwise be bound by MHC class I (York et al., 2003). Many mammalian, biologically-active peptides are excellent substrates for the oligopeptidase actions of thimet oligopeptidase and neurolysin, and some authors have proposed important roles for the enzymes in the catabolism of such peptides. In support of this, evidence has been offered that the predominantly intracellular enzymes are to some extent membrane-bound or secreted.
Statistics for family M3Sequences:16702
Identifiers with PDB entries:8
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M3A
Name Peptidase subfamily M3A
Subfamily type peptidase M03.001 - thimet oligopeptidase (Rattus norvegicus), MEROPS Accession MER0001149 (peptidase unit: 2-687)
Active site residues H473 E474 H477 E502 
Statistics Sequences: 8807
Identifiers: 15
Identifiers with PDB entries: 5
Other databases CATH 3.40.390.10
PFAM PF01432
SCOP 55505
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
thimet oligopeptidaseM03.001Yes
oligopeptidase AM03.004-
peptidyl-dipeptidase DcpM03.005Yes
mitochondrial intermediate peptidaseM03.006-
oligopeptidase MepBM03.009-
Mername-AA154 proteinM03.971-
TOP1 peptidase (Arabidopsis thaliana)M03.A01Yes
TOP2 peptidase (Arabidopsis thaliana)M03.A02Yes
TOPL peptidase (Arabidopsis thaliana)M03.A03-
DDB_G0292362 g.p. (Dictyostelium discoideum)M03.A07-
PF10_0058 g.p. (Plasmodium falciparum)M03.A11-
OCT1 (Arabidopsis thaliana)M03.A12-
Subfamily M3A non-peptidase homologuesnon-peptidase homologue-
Subfamily M3A unassigned peptidasesunassigned-
Subfamily M3B
Name Peptidase subfamily M3B
Subfamily type peptidase M03.007 - oligopeptidase F (Lactococcus lactis), MEROPS Accession MER0001163 (peptidase unit: 290-571)
Active site residues H387 E388 H391 E415 
Statistics Sequences: 5677
Identifiers: 2
Identifiers with PDB entries: 2
Other databases INTERPRO IPR004438
PFAM PF01432
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
oligopeptidase FM03.007Yes
BSSC8_09230 g.p. (Bacillus subtilis)M03.A08-
Subfamily M3B non-peptidase homologuesnon-peptidase homologue-
Subfamily M3B unassigned peptidasesunassignedYes
Subfamily M3C
Name Peptidase subfamily M3C
Subfamily type peptidase M03.010 - Pz-peptidase A (Geobacillus sp. MO-1), MEROPS Accession MER0078856 (peptidase unit: 149-439)
Active site residues H356 E357 H360 E384 
Statistics Sequences: 614
Identifiers: 1
Identifiers with PDB entries: 1
Other databases INTERPRO IPR011976
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Pz-peptidase AM03.010Yes
Subfamily M3C non-peptidase homologuesnon-peptidase homologue-
Subfamily M3C unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
Family M3 unassigned peptidasesunassigned-