Legumain

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• Hydrolysis of proteins and small molecule substrates at -Asn-|-Xaa- bonds.3 Publications

  Manual assertion based on experiment inⁱ

  • Ref.1

    "Cloning and expression of mouse legumain, a lysosomal endopeptidase."
    Chen J.-M., Dando P.M., Stevens R.A.E., Fortunato M., Barrett A.J.
    Biochem. J. 335:111-117(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
  • Ref.3

    "Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases."
    Chen J.-M., Rawlings N.D., Stevens R.A., Barrett A.J.
    FEBS Lett. 441:361-365(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: ACTIVE SITE, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-47; CYS-52; HIS-150 AND CYS-191.
  • Ref.7

    "Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage."
    Zhao L., Hua T., Crowley C., Ru H., Ni X., Shaw N., Jiao L., Ding W., Qu L., Hung L.W., Huang W., Liu L., Ye K., Ouyang S., Cheng G., Liu Z.J.
    Cell Res. 24:344-358(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AUTOCATALYTIC PROCESSING, DISULFIDE BOND, GLYCOSYLATION, PROPEPTIDE, MUTAGENESIS OF ASN-44; ARG-46; HIS-150; GLU-189; CYS-191; ASP-233 AND ASP-311, ACTIVITY REGULATION.

  EC:3.4.22.34

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationⁱ

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>pH dependenceⁱ

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• cysteine-type endopeptidase activity Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.1

    "Cloning and expression of mouse legumain, a lysosomal endopeptidase."
    Chen J.-M., Dando P.M., Stevens R.A.E., Fortunato M., Barrett A.J.
    Biochem. J. 335:111-117(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
• peptidase activity Source: MGI <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Biosynthetic processing of cathepsins and lysosomal degradation are abolished in asparaginyl endopeptidase-deficient mice."
    Shirahama-Noda K., Yamamoto A., Sugihara K., Hashimoto N., Asano M., Nishimura M., Hara-Nishimura I.
    J. Biol. Chem. 278:33194-33199(2003) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• activation of cysteine-type endopeptidase activity Source: MGI
• associative learning Source: ARUK-UCL <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease."
    Zhang Z., Song M., Liu X., Kang S.S., Kwon I.S., Duong D.M., Seyfried N.T., Hu W.T., Liu Z., Wang J.Z., Cheng L., Sun Y.E., Yu S.P., Levey A.I., Ye K.
    Nat. Med. 20:1254-1262(2014) [PubMed] [Europe PMC] [Abstract]
• cellular response to amyloid-beta Source: MGI
• cellular response to calcium ion Source: MGI
• cellular response to hepatocyte growth factor stimulus Source: MGI
• dendritic spine organization Source: ARUK-UCLInferred from genetic interactionⁱ
  • "Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease."
    Zhang Z., Song M., Liu X., Kang S.S., Kwon I.S., Duong D.M., Seyfried N.T., Hu W.T., Liu Z., Wang J.Z., Cheng L., Sun Y.E., Yu S.P., Levey A.I., Ye K.
    Nat. Med. 20:1254-1262(2014) [PubMed] [Europe PMC] [Abstract]
• memory Source: ARUK-UCLInferred from genetic interactionⁱ
  • "Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease."
    Zhang Z., Song M., Liu X., Kang S.S., Kwon I.S., Duong D.M., Seyfried N.T., Hu W.T., Liu Z., Wang J.Z., Cheng L., Sun Y.E., Yu S.P., Levey A.I., Ye K.
    Nat. Med. 20:1254-1262(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of ERBB signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.6

    "Asparagine endopeptidase is required for normal kidney physiology and homeostasis."
    Miller G., Matthews S.P., Reinheckel T., Fleming S., Watts C.
    FASEB J. 25:1606-1617(2011) [PubMed] [Europe PMC] [Abstract]

    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
• negative regulation of gene expression Source: MGI
• negative regulation of multicellular organism growth Source: MGIInferred from mutant phenotypeⁱ
  • "Biosynthetic processing of cathepsins and lysosomal degradation are abolished in asparaginyl endopeptidase-deficient mice."
    Shirahama-Noda K., Yamamoto A., Sugihara K., Hashimoto N., Asano M., Nishimura M., Hara-Nishimura I.
    J. Biol. Chem. 278:33194-33199(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neuron apoptotic process Source: MGI
• positive regulation of cell population proliferation Source: MGI
• positive regulation of endothelial cell chemotaxis Source: MGI
• positive regulation of long-term synaptic potentiation Source: ARUK-UCLInferred from genetic interactionⁱ
  • "Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease."
    Zhang Z., Song M., Liu X., Kang S.S., Kwon I.S., Duong D.M., Seyfried N.T., Hu W.T., Liu Z., Wang J.Z., Cheng L., Sun Y.E., Yu S.P., Levey A.I., Ye K.
    Nat. Med. 20:1254-1262(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitotic cell cycle Source: MGI
• positive regulation of monocyte chemotaxis Source: MGI
• proteolysis Source: UniProtKBInferred from direct assayⁱ
  • Ref.1

    "Cloning and expression of mouse legumain, a lysosomal endopeptidase."
    Chen J.-M., Dando P.M., Stevens R.A.E., Fortunato M., Barrett A.J.
    Biochem. J. 335:111-117(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
• proteolysis involved in cellular protein catabolic process Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.4

    "Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells."
    Morita Y., Araki H., Sugimoto T., Takeuchi K., Yamane T., Maeda T., Yamamoto Y., Nishi K., Asano M., Shirahama-Noda K., Nishimura M., Uzu T., Hara-Nishimura I., Koya D., Kashiwagi A., Ohkubo I.
    FEBS Lett. 581:1417-1424(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
• receptor catabolic process Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.6

    "Asparagine endopeptidase is required for normal kidney physiology and homeostasis."
    Miller G., Matthews S.P., Reinheckel T., Fleming S., Watts C.
    FASEB J. 25:1606-1617(2011) [PubMed] [Europe PMC] [Abstract]

    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
• renal system process Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.6

    "Asparagine endopeptidase is required for normal kidney physiology and homeostasis."
    Miller G., Matthews S.P., Reinheckel T., Fleming S., Watts C.
    FASEB J. 25:1606-1617(2011) [PubMed] [Europe PMC] [Abstract]

    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
• response to acidic pH Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease."
    Zhang Z., Song M., Liu X., Kang S.S., Kwon I.S., Duong D.M., Seyfried N.T., Hu W.T., Liu Z., Wang J.Z., Cheng L., Sun Y.E., Yu S.P., Levey A.I., Ye K.
    Nat. Med. 20:1254-1262(2014) [PubMed] [Europe PMC] [Abstract]
• self proteolysis Source: MGI
• vacuolar protein processing Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypeⁱ

Mutagenesis

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Sites

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

        10         20         30         40         50
MTWRVAVLLS LVLGAGAVPV GVDDPEDGGK HWVVIVAGSN GWYNYRHQAD 
        60         70         80         90        100
ACHAYQIIHR NGIPDEQIIV MMYDDIANSE ENPTPGVVIN RPNGTDVYKG 
       110        120        130        140        150
VLKDYTGEDV TPENFLAVLR GDAEAVKGKG SGKVLKSGPR DHVFIYFTDH 
       160        170        180        190        200
GATGILVFPN DDLHVKDLNK TIRYMYEHKM YQKMVFYIEA CESGSMMNHL 
       210        220        230        240        250
PDDINVYATT AANPKESSYA CYYDEERGTY LGDWYSVNWM EDSDVEDLTK 
       260        270        280        290        300
ETLHKQYHLV KSHTNTSHVM QYGNKSISTM KVMQFQGMKH RASSPISLPP 
       310        320        330        340        350
VTHLDLTPSP DVPLTILKRK LLRTNDVKES QNLIGQIQQF LDARHVIEKS 
       360        370        380        390        400
VHKIVSLLAG FGETAERHLS ERTMLTAHDC YQEAVTHFRT HCFNWHSVTY 
       410        420        430 
EHALRYLYVL ANLCEAPYPI DRIEMAMDKV CLSHY                 

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. Peptidase families
   Classification of peptidase families and list of entries
2. SIMILARITY comments
   Index of protein domains and families
3. MGD cross-references
   Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
4. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references