Family M48

Family

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

M48A

Summary Holotypes Alignment Tree Genomes Literature

M48B

Summary Holotypes Alignment Tree Genomes Literature

M48C

Summary Holotypes Alignment Tree Genomes Literature

Summary for family M48

NamePeptidase family M48 (Ste24 endopeptidase family)
Family type peptidaseM48.001 - Ste24 peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0002635 (peptidase unit: 162-453)
Content of familyPeptidase family M48 contains metalloendopeptidases.
History Identifier created: Handbook of Proteolytic Enzyme, Academic Press, London (1998)
Mating in yeast involves two pheromones, designated the a- and alpha-mating factors. Each is secreted by a different haploid cell type, which then fuse to form a diploid cell. Processing of the a-mating factor from its precursor involves three proteolytic processing events performed by prenyl peptidase 2 (M79.001), Ste24 endopeptidase (M48.001) and Axl1 peptidase (M16.007). Homologues have been found in animals, plants and bacteria.
Catalytic typeMetallo
Active sitePeptidases in family M48 contain a single catalytic zinc ion tetrahedrally co-ordinated by two histidines within an HEXXH motif, an as yet undetermined third residue and water. The glutamate within the HEXXH motif is assumed to be a catalytic residue. Site-directed mutagenesis of the His and Glu residues within the HEXXH motif of Ste24 endopeptidase has confirmed that these are essential for catalysis (Fujimura-Kamada et al., 1997).
Activities and specificitiesEukaryotic peptidases from family M48 have a requirement for substrates that are prenylated at a C-terminal motif known as CAAX, in which A is an aliphatic residue, and the lipid is attached to the cysteine residue. Ste24 endopeptidase is important for the processing of the yeast a-mating factor precursor. Two cleavages are performed: release of a C-terminal tetrapeptide (cleavage occurring at a farnesylated Cys residue, Boyartchuk et al., 1997) followed by release of the first of two N-terminal peptides (Fujimura-Kamada et al., 1997). Although the biological function of human farnesylated-protein converting enzyme 1 (M48.003) is unknown, it is capable of processing the yeast a-mating factor precursor (Schmidt et al., 2000). Homologues from eukaryotes other than yeast probably have broader substrate specificities: the homologue from Arabidopsis thaliana has been shown to cleave several prenylated proteins (Bracha et al., 2002).
InhibitorsThe metal chelator 1,10-phenanthroline has been shown to inhibit Ste24 endopeptidase (Tam et al., 2001).
Molecular structureThe Ste24 endopeptidase is an integral membrane protein with seven transmembrane domains. It resides in the membrane of the endoplasmic reticulum, with the N-terminus in the lumen and the active site and the C-terminus in the cytoplasm (Tam et al., 2001). The HEXXH motif is extracellular but adjacent to a transmembrane domain and therefore close to the membrane surface. The Oma1 endopeptidase (M48.018) is located within the mitochondrial inner membrane (Kaser et al., 2003).
ClanMA
SubclanMA(E)
Basis of clan assignmentFamily M48 is included in clan MA on the basis of comparisons of hidden Markov models derived from the MEROPS family alignments
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsSte24 endopeptidase is essential for mating in Saccharomyces, but it is not essential for viability (Fujimura-Kamada et al., 1997). Without Ste24 endopeptidase, the a-mating factor precursor is not completely processed in the MATa haploid cell type. Human farnesylated-protein converting enzyme 1 may be important for processing prelamin A, a farnesylated protein that is cleaved twice. In cells with a defective peptidase gene, incompletely processed prelamin A accumulates in the nuclear envelope (Pendas et al., 2002). Farnesylated-protein converting enzyme 1 performs the second processing step for prelamin A, releasing a fifteen-residue peptide containing the prenylated C-terminal Cys (Bergo et al., 2002; Pendas et al., 2002). The Oma1 endopeptidase is believed to degrade misfolded membrane proteins, thereby helping to maintain the integrity of the mitochondrial inner membrane (Kaser et al., 2003). In bacteria, the HtpX endopeptidase is induced by heat shock and may be involved in the degradation of abnormal proteins because these accumulate in htpX mutants (Kornitzer et al., 1991.
Pharmaceutical and biotech relevanceDeficiencies in lamin A, a component of the nuclear lamina, lead to abnormalities in the nuclear architecture, and knockouts of farnesylated-protein converting enzyme 1 in mice cause growth retardation, muscular dystrophy and premature death (Pendas et al., 2002; Bergo et al., 2002).
Statistics for family M48Sequences:12399
Identifiers:22
Identifiers with PDB entries:4
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M48A
Name Peptidase subfamily M48A
Subfamily type peptidase M48.001 - Ste24 peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0002635 (peptidase unit: 162-453)
Active site residues H297 E298 H301 E390 
Statistics Sequences: 4554
Identifiers: 9
Identifiers with PDB entries: 2
Other databases INTERPRO IPR001915
PANTHER PTHR10120
PFAM PF01435
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Ste24 peptidaseM48.001Yes
farnesylated-protein converting enzyme 1M48.003Yes
Mername-AA052 peptidaseM48.008-
YhfN peptidaseM48.009-
STE24 peptidase (Sarcomastigophora-type)M48.020-
CG9002 protein (Drosophila melanogaster)M48.A05-
CG9001 protein (Drosophila melanogaster)M48.A06-
DDB_G0270268 g.p. (Dictyostelium discoideum)M48.A07-
zmpste24 g.p. (Dictyostelium discoideum-type)M48.A08-
subfamily M48A non-peptidase homologuesnon-peptidase homologue-
subfamily M48A unassigned peptidasesunassigned-
Subfamily M48B
Name Peptidase subfamily M48B
Subfamily type peptidase M48.002 - HtpX peptidase (Escherichia coli), MEROPS Accession MER0002637 (peptidase unit: 78-286)
Active site residues H139 E140 H143 E222 
Statistics Sequences: 5042
Identifiers: 5
Identifiers with PDB entries: 1
Other databases INTERPRO IPR001915
PANTHER PTHR10120
PFAM PF01435
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
HtpX peptidaseM48.002Yes
HtpX-2 peptidaseM48.004-
PAB0555-type putative peptidaseM48.010-
M48.021-
PF1597 g.p. (Pyrococcus furiosus)M48.A10-
yxkI g.p. (Bacillus subtilis)M48.A11-
subfamily M48B non-peptidase homologuesnon-peptidase homologue-
subfamily M48B unassigned peptidasesunassigned-
Subfamily M48C
Name Peptidase subfamily M48C
Subfamily type peptidase M48.018 - Oma1 peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0026545 (peptidase unit: 56-325)
Active site residues H203 E204 H207 E257 
Statistics Sequences: 2653
Identifiers: 7
Identifiers with PDB entries: 1
Other databases INTERPRO IPR001915
PANTHER PTHR22726
PFAM PF01435
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
metalloprotease-related protein-1M48.017-
Oma1 peptidaseM48.018-
GSU1437 putative peptidaseM48.019Yes
At5g51740 (Arabidopsis thaliana)-type peptidaseM48.A01-
YcaL protein (Escherichia coli)M48.A03-
low osmolarity induced peptidaseM48.A04-
BepA (Escherichia coli)M48.A12-
subfamily M48C non-peptidase homologuesnon-peptidase homologue-
subfamily M48C unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
DDB_G0286165 g.p. (Dictyostelium discoideum)M48.A09-
family M48 non-peptidase homologuesnon-peptidase homologue-
family M48 unassigned peptidasesunassigned-