Family M43

Family

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

M43A

Summary Holotypes Alignment Tree Genomes Literature

M43B

Summary Holotypes Alignment Tree Genomes Literature

Summary for family M43

NamePeptidase family M43 (cytophagalysin family)
Family type peptidaseM43.001 - cytophagalysin (Cytophaga sp.), MEROPS Accession MER0002084 (peptidase unit: 67-282)
Content of familyPeptidase family M43 contains metallo-endopeptidases.
History Identifier created: Handbook of Proteolytic Enzyme, Academic Press, London (1998)
Catalytic typeMetallo
Active siteFamily 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 specificitiesCytophagalysin (M43.001) cleaves beta-casein at Pro63Gly64 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.
InhibitorsCytophagalysin 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 structurePappalysin 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.
ClanMA
SubclanMA(M)
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 details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsIn 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 relevanceIt 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 M43Sequences:1785
Identifiers:6
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 H231 E232 H235 H241 
Statistics Sequences: 25
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
cytophagalysinM43.001-
subfamily M43A non-peptidase homologuesnon-peptidase homologue-
subfamily M43A unassigned peptidasesunassigned-
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 H563 E564 H567 H573 M637 
Statistics Sequences: 1753
Identifiers: 5
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-1M43.004-
pappalysin-2M43.005-
ulilysinM43.007Yes
Mername-AA293 peptidaseM43.008-
subfamily M43B non-peptidase homologuesnon-peptidase homologue-
subfamily M43B unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
family M43 unassigned peptidasesunassigned-