Peptidase A8, signal peptidase II (IPR001872)

Short name: Peptidase_A8

Family relationships



Aspartic endopeptidases EC:3.4.23. of vertebrate, fungal and retroviral origin have been characterised [PMID: 1455179]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [PMID: 10625704] and archaean preflagellin have been described [PMID: 16983194, PMID: 14622420].

Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.

This group of aspartic peptidases belong to the MEROPS peptidase family A8 (signal peptidase II family, clan AC). The catalytic residues have not been identified, but three conserved aspartates can be identified from sequence alignments. The type example is the Escherichia coli lipoprotein signal peptidase or SPase II (EC: This enzyme recognises a conserved sequence and cuts in front of a cysteine residue to which a glyceride-fatty acid lipid is attached. SPase II is an integral membrane protein that is anchored in the membrane.

Bacterial cell walls contain large amounts of murein lipoprotein, a small protein that is both N-terminally bound to lipid and attached to membrane peptidoglycan (murein) through the epsilon-amino group of its C-terminal lysine residue [PMID: 7674916]. Secretion of this lipoprotein is facilitated by the action of the lipoprotein signal peptidases in this entry, located in the inner membrane [PMID: 7674916, PMID: 6368552]. They enzyme are inhibited by globomycin and also by pepstatin, suggesting that they are aspartic peptidases [PMID: 7674916].

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004190 aspartic-type endopeptidase activity

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns