Family M43
Summary for family M43
| Name | Peptidase family M43 (cytophagalysin family) |
|---|---|
| Family type peptidase | M43.001 - cytophagalysin (Cytophaga sp.), MEROPS Accession MER0002084 (peptidase unit: 67-282) |
| Content of family | Peptidase family M43 contains metallo-endopeptidases. |
| History |
Identifier created: Handbook of Proteolytic Enzyme, Academic Press, London (1998) |
| Catalytic type | Metallo |
| Active site | Family M43 members contain three zinc binding histidines and a catalytic glutamate in an HEXXHXXGXXH motif. There are two subfamilies, and the sequences of peptidases in subfamily M43B contain a conserved methionine (C-terminal to the HEXXHXXGXXH motif) found in other members of clan MA(M). |
| Activities and specificities | Cytophagalysin (M43.001) cleaves beta-casein at Pro63 Gly64 and Met102Ala103. Both pappalysin-1 (M43.004) and papplysin-2 (M43.005) can cleave insulin-like growth factor binding-protein 5 (IGFBP-5) at Ser143Lys144 (Laursen et al., 2001). Pappalysin-1 can cleave IGFBP-1 at Met135Lys136 and also IGFBP-4. Boldt et al. (2001) also showed that pappalysin-1 can cleave itself at Phe386Asn387, causing a loss of peptidase activity. |
| Inhibitors | Cytophagalysin is inhibited by the metal chelator EDTA at millimolar concentrations Kamio & Sasagawa, 2004. Pappalysin-1 is also inhibited by metal chelating agents, including EDTA and 1,10-phenanthroline. |
| Molecular structure | Pappalysin is secreted as a 400-kDa dimer. The majority of sequences in family M43 (in subfamily B) show a conserved Met residue C-terminal to the zinc-binding motif that presumably indicates the presence of a "Met-turn" analogous to that in astacin (M12.001), the type peptidase of subclan M of clan MA. |
| Clan | MA |
| Subclan | MA(M) |
| Basis of clan assignment | Predicted 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 | details | ||
| Protozoa | details | ||
| Fungi | - | ||
| Plants | details | ||
| Animals | details | ||
| Viruses | details |
| Biological functions | In vivo pappalysin circulates bound to proMBP, and in the complex the proteolytic activity of pappalysin-1 is reduced more than 100-fold (Overgaard et al., 2000). | |
| Pharmaceutical and biotech relevance | It is recognised that low first trimester levels of pappalysin-1 correlate with Down"s syndrome (Haddow et al., 1998). Pappalysin-1 is also present in unstable atherosclerotic plaques, and is a marker of acute coronary syndromes (Bayes-Genis et al., 2001). | |
| Statistics for family M43 | Sequences: | 1491 |
| Identifiers: | 7 | |
| Identifiers with PDB entries: | 1 | |
| Downloadable files | Sequence library (FastA format) | |
| Sequence alignment (FastA format) | ||
| Phylogenetic tree (Newick format) | ||
| Subfamily M43A | ||||
| Name | Peptidase subfamily M43A | |||
| Subfamily type peptidase | M43.001 - cytophagalysin (Cytophaga sp.), MEROPS Accession MER0002084 (peptidase unit: 67-282) | |||
| Active site residues | E232 | |||
| Statistics | Sequences: | 49 | ||
| Identifiers: | 1 | |||
| Identifiers with PDB entries: | 0 | |||
| Other databases | INTERPRO | IPR008754 | ||
| PFAM | PF05572 | |||
| Downloadable files | Sequence library [FastA format] | Sequence alignment [FastA format] | Phylogenetic tree [Newick format] | |
| Peptidases and Homologues | MEROPS ID | Structure |
|---|---|---|
| cytophagalysin | M43.001 | - |
| Subfamily M43A non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M43A unassigned peptidases | unassigned | - |
| Subfamily M43B | ||||
| Name | Peptidase subfamily M43B | |||
| Subfamily type peptidase | M43.004 - pappalysin-1 (Homo sapiens), MEROPS Accession MER0002217 (peptidase unit: 442-873) | |||
| Active site residues | E564 M637 | |||
| Statistics | Sequences: | 1422 | ||
| Identifiers: | 6 | |||
| Identifiers with PDB entries: | 1 | |||
| Other databases | INTERPRO | IPR008754 | ||
| PANTHER | PTHR19325 | |||
| PFAM | PF05572 | |||
| Downloadable files | Sequence library [FastA format] | Sequence alignment [FastA format] | Phylogenetic tree [Newick format] | |
| Peptidases and Homologues | MEROPS ID | Structure |
|---|---|---|
| metallopeptidase MEP1 (Metarhizium-type) | M43.002 | - |
| pappalysin-1 | M43.004 | - |
| pappalysin-2 | M43.005 | - |
| ulilysin (Methanosarcina acetivorans) | M43.007 | Yes |
| Mername-AA293 peptidase | M43.008 | - |
| mirolysin (Tannerella forsythia) | M43.009 | - |
| Subfamily M43B non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M43B unassigned peptidases | unassigned | - |
| Peptidases not assigned to subfamily |
| Peptidases and Homologues | MEROPS ID | Structure |
|---|---|---|
| Family M43 unassigned peptidases | unassigned | - |
