Family M67
Summary for family M67
| Family type peptidase | M67.001 - PSMD14 peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0003198 (peptidase unit: 1-167) |
| Content of family | Family 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 type | Metallo |
| Active site | Peptidases 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 specificities | AMSH 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 structure | The 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). |
| Clan | MP |
| Biological functions | For 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 relevance | The 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 M67 | Sequences: | 7179 |
| Identifiers: | 31 |
| Identifiers with PDB entries: | 15 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| PSMD14 peptidase | M67.001 | Yes |
| Csn5 peptidase | M67.002 | Yes |
| Brcc36 isopeptidase | M67.004 | Yes |
| histone H2A deubiquitinase MYSM1 | M67.005 | Yes |
| C6.1A-like putative peptidase | M67.007 | - |
| putative peptidase (Homo sapiens chromosome 2) | M67.008 | - |
| MPN domain-containing protein (Homo sapiens) | M67.011 | - |
| COP9 signalosome subunit 6 | M67.972 | Yes |
| 26S proteasome non-ATPase regulatory subunit 7 | M67.973 | Yes |
| IFP38 peptidase homologue | M67.975 | - |
| Mername-AA307 protein | M67.976 | - |
| At1g22920 (Arabidopsis thaliana) | M67.A01 | - |
| At1g71230 (Arabidopsis thaliana) | M67.A02 | - |
| At1g80210 (Arabidopsis thaliana) | M67.A03 | - |
| F37A4.5 protein (Caenorhabditis elegans) | M67.A10 | Yes |
| 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 homologues | non-peptidase homologue | - |
| Subfamily M67A unassigned peptidases | unassigned | Yes |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| STAM-binding protein-like 1 | M67.003 | Yes |
| STAMBP isopeptidase | M67.006 | Yes |
| At1g48790 (Arabidopsis thaliana)-type peptidase | M67.A04 | - |
| At1g10600 (Arabidopsis thaliana)-type peptidase | M67.A05 | - |
| At4g16144 (Arabidopsis thaliana)-type peptidase | M67.A06 | - |
| Cg2224 protein (Drosophila melanogaster) | M67.A09 | - |
| sst2 g.p. (Schizosaccharomyces pombe) | M67.A14 | Yes |
| DG1039 g.p. (Dictyostelium discoideum) | M67.A15 | - |
| Subfamily M67C non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M67C unassigned peptidases | unassigned | - |
|
Peptidases not assigned to subfamily
|
| Peptidases and Homologues |
MEROPS ID |
Structure |
| Mername-AA168 protein | M67.971 | Yes |
| eukaryotic translation initiation factor 3 subunit F | M67.974 | Yes |
| Family M67 non-peptidase homologues | non-peptidase homologue | - |
| Family M67 unassigned peptidases | unassigned | - |
