Detail Information for IndEnz0002002256
IED ID IndEnz0002002256
Enzyme Type ID protease002256
Protein Name Legumain
EC 3.4.22.34
Asparaginyl endopeptidase
Protease, cysteine 1
Gene Name LGMN PRSC1
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MVWKVAVFLSVALGIGAVPIDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRPNGTDVYQGVPKDYTGEDVTPQNFLAVLRGDAEAVKGIGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNEDLHVKDLNETIHYMYKHKMYRKMVFYIEACESGSMMNHLPDNINVYATTAANPRESSYACYYDEKRSTYLGDWYSVNWMEDSDVEDLTKETLHKQYHLVKSHTNTSHVMQYGNKTISTMKVMQFQGMKRKASSPVPLPPVTHLDLTPSPDVPLTIMKRKLMNTNDLEESRQLTEEIQRHLDARHLIEKSVRKIVSLLAASEAEVEQLLSERAPLTGHSCYPEALLHFRTHCFNWHSPTYEYALRHLYVLVNLCEKPYPLHRIKLSMDHVCLGHY
Enzyme Length 433
Uniprot Accession Number Q99538
Absorption
Active Site ACT_SITE 148; /evidence=ECO:0000305|PubMed:23776206; ACT_SITE 189; /note=Nucleophile; /evidence=ECO:0000269|PubMed:23776206
Activity Regulation ACTIVITY REGULATION: Inhibited by CST6. {ECO:0000269|PubMed:30425301}.
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=Hydrolysis of proteins and small molecule substrates at -Asn-|-Xaa- bonds.; EC=3.4.22.34; Evidence={ECO:0000269|PubMed:23776206};
DNA Binding
EC Number 3.4.22.34
Enzyme Function FUNCTION: Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. Required for normal lysosomal protein degradation in renal proximal tubules. Required for normal degradation of internalized EGFR. Plays a role in the regulation of cell proliferation via its role in EGFR degradation (By similarity). May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. {ECO:0000250, ECO:0000269|PubMed:23776206}.
Temperature Dependency
PH Dependency BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 5.5 for the free enzyme, and pH 6 in the presence of bound integrins. {ECO:0000269|PubMed:23776206};
Pathway
nucleotide Binding
Features Active site (2); Alternative sequence (3); Beta strand (11); Chain (1); Disulfide bond (2); Glycosylation (4); Helix (11); Mutagenesis (2); Natural variant (1); Propeptide (1); Sequence conflict (1); Signal peptide (1); Site (1); Turn (4)
Keywords 3D-structure;Alternative splicing;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Lysosome;Protease;Reference proteome;Signal;Thiol protease;Zymogen
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Lysosome {ECO:0000250}.
Modified Residue
Post Translational Modification PTM: Glycosylated. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23776206}.; PTM: Activated by autocatalytic processing at pH 4. {ECO:0000269|PubMed:11085925}.
Signal Peptide SIGNAL 1..17; /evidence=ECO:0000269|PubMed:11085925
Structure 3D X-ray crystallography (11)
Cross Reference PDB 4AW9; 4AWA; 4AWB; 4FGU; 4N6N; 4N6O; 5LU8; 5LU9; 5LUA; 5LUB; 7O50;
Mapped Pubmed ID 10052453; 12860980; 15100291; 15788679; 18166152; 18292509; 18374643; 18377911; 18820679; 18931679; 19453521; 19615732; 20074384; 20536387; 20562859; 21402738; 21988832; 22232165; 22441772; 22718532; 22902879; 23124822; 23160071; 23326369; 23416715; 23640887; 23942113; 24023813; 24407422; 24610907; 24742492; 25326800; 25605174; 25630877; 26496610; 26549211; 26607955; 26802645; 26846877; 27102302; 27464733; 27590439; 27793040; 27940038; 27993111; 28162997; 28345579; 28630039; 28671665; 29414692; 30135302; 30429518; 30676070; 31060209; 31400201; 31870625; 32080801; 32506655; 33121976; 33383559; 34582975; 34621593; 8134367;
Motif
Gene Encoded By
Mass 49,411
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda 3.4.22.34;