Family M67


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


Summary Holotypes Alignment Tree Genomes Literature


Summary Holotypes Alignment Tree Genomes Literature


Summary Holotypes Alignment Tree Genomes Literature

Summary for family M67

Family type peptidaseM67.001 - RPN11 peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0003198 (peptidase unit: 1-167)
Content of familyFamily M67 contains isopeptidases that release ubiquitin from ubiquitinated proteins.
History Identifier created: MEROPS 6.1 (10 January 2003)
Proteins that are destined for degradation by the 26S proteasome (XT01-002) are tagged with polyubiquitin. There are many peptidases that release ubiquitin from tagged proteins but the majority of them are cysteine peptidases (see families C12, C19, C64 and C65). However, the Poh1 peptidase (M67.001) also releases ubiquitin from tagged proteins, but it is a metallopeptidase and one of the components of the PA700 multisubunit complex. This complex binds to the 20S proteasome (XT01-001) to form the 26S proteasome (Yao & Cohen, 2002).
Catalytic typeMetallo
Active sitePeptidases in family M67 bind one zinc ion per molecule. The metal ligands and an active site residue have been identified by site-directed mutagenesis (Maytal-Kivity et al., 2002; Verma et al., 2002). The metal ligands are two histidines within the motif HXH and an aspartate C-terminal to this motif. A glutamate N-terminal to this motif is a catalytic residue (see the Alignment).
Activities and specificitiesAMSH peptidase (M67.006) has been shown to be an isopeptidase cleaving Lys48-linked tetra-ubiquitin and Lys63-linked polyubiquitin chains (McCullough et al., 2004).
Molecular structureThe tertiary structure determined for JAMM-like protein (M67.010) from Archeaoglobus fulgidus shows a single domain consisting of a five-stranded beta sheet between two helices (Tran et al., 2003). The structure is unlike that of any other peptidase and family M67 is the type family of clan MP. Unlike many other metallopeptidases, the histidine zinc ligands are in beta structures rather than helices. The Poh1 peptidase is a larger, multidomain protein with the peptidase unit residing in an N-terminal domain (Rinaldi et al., 2004).
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsFor proteins to be degraded by the proteasome they must first be unfolded and the ubiquitin tags removed; these are the functions of the PA700, 19S and COP9 complexes. AMSH is associated with endosomes affecting the rate of turnover of receptor proteins which are ubiquitinated and sorted to the lysosome for degradation (McCullough et al., 2004). The Poh1 peptidase also functions to maintain mitochondrial integrity, by means of a C-terminal domain (Rinaldi et al., 2004). The first functional characterization of a prokaryotic peptidase (M67.010) with the JAMM motif was provided by Burns et al. (2005).
Pharmaceutical and biotech relevanceThe Poh1 peptidase is overexpressed in mammalian cells in response to certain cytotoxic drugs and may contribute to the escape of tumor cells from cytotoxic drugs (Spataro et al., 2002).
Statistics for family M67Sequences:7438
Identifiers with PDB entries:12
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M67A
Name Peptidase subfamily M67A
Subfamily type peptidase M67.001 - RPN11 peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0003198 (peptidase unit: 1-167)
Active site residues E48 H109 H111 D122 
Statistics Sequences: 5226
Identifiers: 18
Identifiers with PDB entries: 6
Other databases INTERPRO IPR000555
PFAM PF01398
PFAM PF05021
PFAM PF14464
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
RPN11 peptidaseM67.001Yes
Csn5 peptidaseM67.002Yes
Brcc36 isopeptidaseM67.004-
histone H2A deubiquitinase MYSM1M67.005Yes
C6.1A-like putative peptidaseM67.007-
putative peptidase (Homo sapiens chromosome 2)M67.008-
MPN domain-containing protein (Homo sapiens)M67.011-
COP9 signalosome subunit 6M67.972Yes
26S proteasome non-ATPase regulatory subunit 7M67.973Yes
IFP38 peptidase homologueM67.975-
Mername-AA307 proteinM67.976-
At1g22920 (Arabidopsis thaliana)M67.A01-
At1g71230 (Arabidopsis thaliana)M67.A02-
At1g80210 (Arabidopsis thaliana)M67.A03-
F37A4.5 protein (Caenorhabditis elegans)M67.A10-
rpn-11 g.p. (Caenorhabditis elegans)M67.A11-
mybH g.p. (Dictyostelium discoideum)M67.A12-
csn5 g.p. (Dictyostelium discoideum)M67.A13-
subfamily M67A non-peptidase homologuesnon-peptidase homologue-
subfamily M67A unassigned peptidasesunassignedYes
Subfamily M67B
Name Peptidase subfamily M67B
Subfamily type peptidase M67.010 - JAMM-like protein ({Archaeoglobus}-type) (Archaeoglobus fulgidus), MEROPS Accession MER0031571 (peptidase unit: 1-121)
Active site residues E22 H67 H69 D80 
Statistics Sequences: 558
Identifiers: 2
Identifiers with PDB entries: 1
Other databases CATH
PFAM PF01398
PFAM PF14464
SCOP 102713
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Mec peptidaseM67.009-
JAMM-like protein (Archaeoglobus-type)M67.010Yes
subfamily M67B non-peptidase homologuesnon-peptidase homologue-
subfamily M67B unassigned peptidasesunassigned-
Subfamily M67C
Name Peptidase subfamily M67C
Subfamily type peptidase M67.006 - STAMBP isopeptidase (Homo sapiens), MEROPS Accession MER0030146 (peptidase unit: 251-383)
Active site residues E280 H335 H337 D348 
Statistics Sequences: 803
Identifiers: 8
Identifiers with PDB entries: 3
Other databases INTERPRO IPR000555
PFAM PF01398
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Mername-AA165 peptidaseM67.003Yes
STAMBP isopeptidaseM67.006Yes
At1g48790 (Arabidopsis thaliana)-type peptidaseM67.A04-
At1g10600 (Arabidopsis thaliana)-type peptidaseM67.A05-
At4g16144 (Arabidopsis thaliana)-type peptidaseM67.A06-
Cg2224 protein (Drosophila melanogaster)M67.A09-
sst2 g.p. (Schizosaccharomyces pombe)M67.A14Yes
DG1039 g.p. (Dictyostelium discoideum)M67.A15-
subfamily M67C non-peptidase homologuesnon-peptidase homologue-
subfamily M67C unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
Mername-AA168 proteinM67.971Yes
eukaryotic translation initiation factor 3 subunit FM67.974Yes
family M67 non-peptidase homologuesnon-peptidase homologue-
family M67 unassigned peptidasesunassigned-