Summary for peptidase M16.011: falcilysin

Summary Alignment Tree Sequences Sequence features Distribution Literature Substrates Inhibitors

 

Names
MEROPS Namefalcilysin
Other namesmetalloendopeptidase (Plasmodium falciparum)
Name and HistoryDegradation of hemoglobin by the intra-erythrocytic stages of the malaria parasite is predominantly undertaken by plasmepsins and falcipains in the acidic food vacuole (Gluzman et al., 1994). However, 24 cleavages could not be attributed to known peptidases, which led to the discovery of falcilysin (Eggleson et al., 1999).
Domain architecture
MEROPS Classification
Classification Clan ME >> Subclan (none) >> Family M16 >> Subfamily C >> M16.011
Holotypefalcilysin (Plasmodium falciparum) (peptidase unit: 121-583), MERNUM MER0015088
History Identifier created: MEROPS 5.1 (22 June 2000)
Activity
Catalytic typeMetallo
NC-IUBMBNot yet included in IUBMB recommendations.
Proteolytic eventsCutDB database (7 cleavages)
SpecificityFalcilysin is an oligopeptidase with a preference for peptides 11-15 amino acids in length, but can cleave peptides up to twenty residues long (Eggleson et al., 1999). Specificity differs with pH. From substrate specificity profiling and analysis of hemoglobin cleavage sites, at acidic pH there is a preference for asparagine in P4, polar or charged residues (especially Ser, Thr and Ile) in P1, glutamine or a charged residue in P2, and a charged residue in P4'. At neutral pH, falcilysin shows a strong preference for Arg or Ser at P1 and Gly or Arg at P3 (Murata & Goldberg, 2003).
pH optimumFalcilysin displays both acidic (5.2) and neutral (7.2) pH optima (Murata & Goldberg, 2003).
LocationFalcilysin is peripheral membrane protein located in food vacuoles of the intra-erythrocytic stages in the life cycle (Murata & Goldberg, 2003), apicoplast and other uncharacterized vesicular structures (Ponpuak et al., 2007). It is also expressed in the cytoplasm, which suggests falcilysin has another as yet unidentified role (Murata & Goldberg, 2003).
PhysiologyIn addition to the further degradation of peptides derived from hemoglobin in the food vacuole, in the apicoplast falcilysin degrades free transit peptides liberated by a stromal processing peptidase (Ponpuak et al., 2007).
Contributing authorsNeil D. Rawlings, InterPro, Proteins Cluster, EMBL European Bioinformatics Institute, Hinxton, Cambridgeshire, CB10 1SD, UK
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/k/kdlScissile bond-/-/-/- (based on 10 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 1 0 0 0 1 0 0 1
Pro 0 0 0 0 0 0 2 0
Ala 3 2 0 0 0 0 2 0
Val 0 1 1 0 1 1 1 0
Leu 2 1 0 2 1 1 2 0
Ile 1 0 0 0 0 1 0 0
Met 0 0 0 0 0 1 0 0
Phe 0 1 0 0 1 2 0 0
Tyr 0 1 0 0 1 0 0 0
Trp 1 0 0 0 0 0 0 0
Ser 0 0 2 0 0 1 1 1
Thr 1 2 0 1 0 0 0 0
Cys 0 0 0 0 0 0 0 0
Asn 0 0 0 0 0 1 1 2
Gln 0 0 2 0 1 0 0 1
Asp 0 0 0 2 2 0 0 1
Glu 0 0 0 0 0 0 1 0
Lys 0 1 3 4 1 0 0 2
Arg 0 0 0 1 1 2 0 0
His 1 1 2 0 0 0 0 2