Summary for peptidase C13.004: legumain, animal-type

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namelegumain, animal-type
Other namesAEP, asparaginyl endopeptidase (AEP), LGMN g.p. (Homo sapiens), osteoclast inhibitory peptide 2, PRSC1 g.p. [obs.] (Homo sapiens)
Domain architecture
MEROPS Classification
Classification Clan CD >> Subclan (none) >> Family C13 >> Subfamily (none) >> C13.004
Holotypelegumain, animal-type (Homo sapiens), Uniprot accession Q99538 (peptidase unit: 25-286), MERNUM MER0001800
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00098
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.34
EnzymologyBRENDA database
Proteolytic eventsCutDB database (17 cleavages)
Activity statushuman: active (Chen et al., 1997)
mouse: active (Chen et al., 1998)
SpecificityAlthough it is frequently describes as an asparaginyl endopeptidase, only certain asparagine bonds are cleaved. At low pH, aspartic bonds are cleaved (Dando et al., 1999).
pH optimumMaximally active at pH 5.8, but stable in the range pH 4-6.
Special substrateZ-Ala-Ala-Asn-NHMec
StructureLegumain is synthesized as a preproprotein with an N-terminal signal peptide and a C-terminal activation peptide.
LocationLysosomal.
PhysiologyImportant for degradation of cytoplasmic and extracellular proteins in the lysosome. Implicated in processing of some antigens for the MHC class II immune response (Manoury et al., 1998).
Biological aspectsLegumain releases its own C-terminal propeptide (Chen et al., 2000). Animal legumain is surprisingly absent in insects.
KnockoutKnockout mice show that legumain is essential for processing of cathepsin L (C01.032), but not for class II MHC-restricted antigen presentation (Maehr et al., 2005).
Distinguishing featuresLegumain is unaffected by E-64, but is inhibited by some cystatins. Specificity for asparagine is unique amongst cysteine peptidases.
Pathways KEGGAntigen processing and presentation
KEGGLysosome
Contributing authorsNeil D. Rawlings, Bateman Group, Wellcome Trust Sanger Institute and EMBL European Bioinformatics Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/LGMN
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/NScissile bond-/-/-/- (based on 81 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 3 4 5 0 7 3 2 3
Pro 1 9 5 0 0 6 4 4
Ala 6 10 6 0 8 5 6 3
Val 5 6 4 0 5 11 6 4
Leu 6 7 3 0 4 7 11 6
Ile 8 5 5 0 5 6 6 7
Met 3 1 1 0 2 2 2 1
Phe 3 4 3 0 3 1 1 2
Tyr 1 2 2 0 4 2 2 4
Trp 1 0 1 0 0 2 1 2
Ser 4 7 6 0 3 3 6 6
Thr 5 3 10 0 2 4 7 3
Cys 1 1 2 0 0 1 2 3
Asn 2 4 6 76 6 3 1 4
Gln 5 6 2 0 3 2 1 1
Asp 5 1 4 5 8 3 6 3
Glu 3 1 5 0 6 4 4 7
Lys 3 4 5 0 7 6 5 2
Arg 5 3 3 0 2 4 2 5
His 3 2 2 0 1 1 0 2
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
LGMN 14q32.1 ENSG00000100600 5641 LGMN 602620
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Lgmn 12:F1 ENSMUSG00000021190 19141 MGI:1330838