Family A8


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family A8

NamePeptidase family A8 (signal peptidase II family)
Family type peptidaseA08.001 - signal peptidase II (Escherichia coli), MEROPS Accession MER0001313 (peptidase unit: 1-164)
Content of familyPeptidase family A8 contains an endopeptidase, the bacterial signal peptidase II.
History Identifier created: Proteolysis in Cell Function, pp13-21, IOS Press, Amsterdam (1997)
Catalytic typeAspartic
Active site residuesD114 D141 
Active siteTwo aspartate residues have been shown by site-directed mutagenesis to be essential for activity (Tjalsma et al., 1999). These occur in the motifs GNXXDRX and FNXAD where X is a hydrophobic residue.
Activities and specificitiesCleavage of the prelipoprotein occurs on the amino side of a modified cysteine residue, the thiol group of which is substituted with a diacylglyceryl group (an activity of phosphatidylglycerol:prolipoprotein diacylglyceryl transferase). The consensus around the cleavage site is known as the 'lipobox sequence' and is Leu-Xaa-YaaCys in which Xaa is Ala or Ser and Yaa is Gly or Ala. The specificity of the peptidase was examined in detail by Gonnet et al. (2004).
InhibitorsThe cyclic pentapeptide antibiotic globomycin is a potent noncompetitive inhibitor. Pepstatin, Tos-Arg-OMe and mercuric chloride also inhibit at concentrations below 1 mM (Sankaran, 2004).
Molecular structureSignal peptidase II is membrane bound with four transmembrane domains. The active site is close to the membrane surface between transmembrane domains three and four on the periplasmic side. Although the tertiary structure has not been determined, the fold is unlikely to be similar to that of any other aspartic peptidase and so family A8 is assigned to its own clan, AC.
Basis of clan assignmentType family of clan AC.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsSignal peptidase II removes the signal peptide from the N-terminus of the murein prolipoprotein, an essential step in the production of the bacterial cell wall. Homologues are known from nearly every bacterial genome so far completely sequenced. A few bacteria, including Pseudomonas fluorescens and Staphylococcus epidermidis, contain two family A8 homologues.
ReviewsSankaran (2004)
Statistics for family A8Sequences:6504
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR001872
PFAM PF01252
Peptidases and Homologues MEROPS ID Structure
signal peptidase IIA08.001Yes
family A8 non-peptidase homologuesnon-peptidase homologue-
family A8 unassigned peptidasesunassigned-