UniProtKB - O89017 (LGMN_MOUSE)
Protein
Legumain
Gene
Lgmn
Organism
Mus musculus (Mouse)
Status
Functioni
Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. 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.4 Publications
Catalytic activityi
- Hydrolysis of proteins and small molecule substrates at -Asn-|-Xaa- bonds.3 Publications EC:3.4.22.34
Activity regulationi
Inhibited by cystatin-C.1 Publication
pH dependencei
Optimum pH is 6.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 150 | 1 Publication | 1 | |
Active sitei | 191 | Nucleophile1 Publication | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: UniProtKB
- peptidase activity Source: MGI
GO - Biological processi
- activation of cysteine-type endopeptidase activity Source: MGI
- associative learning Source: ARUK-UCL
- 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-UCL
- memory Source: ARUK-UCL
- negative regulation of ERBB signaling pathway Source: UniProtKB
- negative regulation of gene expression Source: MGI
- negative regulation of multicellular organism growth Source: MGI
- 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-UCL
- positive regulation of mitotic cell cycle Source: MGI
- positive regulation of monocyte chemotaxis Source: MGI
- proteolysis Source: UniProtKB
- proteolysis involved in cellular protein catabolic process Source: UniProtKB
- receptor catabolic process Source: UniProtKB
- renal system process Source: UniProtKB
- response to acidic pH Source: ARUK-UCL
- self proteolysis Source: MGI
- vacuolar protein processing Source: GO_Central
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Enzyme and pathway databases
BRENDAi | 3.4.22.34, 3474 |
Reactomei | R-MMU-1679131, Trafficking and processing of endosomal TLR R-MMU-2132295, MHC class II antigen presentation |
Protein family/group databases
MEROPSi | C13.004 |
Names & Taxonomyi
Protein namesi | Recommended name: Legumain (EC:3.4.22.34)Alternative name(s): Asparaginyl endopeptidase Protease, cysteine 1 |
Gene namesi | Name:Lgmn Synonyms:Prsc1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1330838, Lgmn |
Subcellular locationi
Lysosome
- Lysosome 2 Publications
Endosome
- late endosome Source: MGI
Extracellular region or secreted
- extracellular region Source: MGI
Lysosome
- lysosome Source: UniProtKB
Other locations
- apical part of cell Source: MGI
- cytoplasm Source: MGI
- perinuclear region of cytoplasm Source: MGI
Keywords - Cellular componenti
LysosomePathology & Biotechi
Disruption phenotypei
Young mice initially display no obvious phenotype, but fail to gain weight normally. Mutant mice display pale kidneys with abnormal proliferation of proximal tubule cells, proximal tubule hyperplasia and develop kidney interstitium fibrosis. After 6 months, mutant mice display a decreased glomerular filtration rate, increased plasma creatinine levels and proteinuria. Glomerular lysosomes do not show a generalized defect in protein catabolism. Instead they show defects in the degradation of a set of target proteins, including EGFR.2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 44 | N → A: Nearly abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 46 | R → A: Nearly abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 47 | H → A: 54% Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 52 | C → S: No loss of activity. 1 Publication | 1 | |
Mutagenesisi | 150 | H → A: Complete loss of activity. Abolishes autocatalytic processing. 2 Publications | 1 | |
Mutagenesisi | 189 | E → A: Abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 191 | C → A or S: Abolishes enzyme activity. 2 Publications | 1 | |
Mutagenesisi | 233 | D → A: Abolishes enzyme activity. Abolishes autocatalytic processing. 1 Publication | 1 | |
Mutagenesisi | 311 | D → A: Nearly abolishes enzyme activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL1949492 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | By similarityAdd BLAST | 17 | |
ChainiPRO_0000026504 | 18 – 325 | LegumainAdd BLAST | 308 | |
PropeptideiPRO_0000026505 | 326 – 435 | Add BLAST | 110 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 93 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 169 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 265 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 274 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 380 ↔ 414 | 1 Publication | ||
Disulfide bondi | 392 ↔ 431 | 1 Publication |
Post-translational modificationi
Glycosylated.1 Publication
Activated by autocatalytic processing at pH 4.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 325 – 326 | Cleavage; by autolysis | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, ZymogenProteomic databases
EPDi | O89017 |
jPOSTi | O89017 |
MaxQBi | O89017 |
PaxDbi | O89017 |
PeptideAtlasi | O89017 |
PRIDEi | O89017 |
PTM databases
GlyConnecti | 2463, 1 N-Linked glycan (1 site) |
GlyGeni | O89017, 4 sites |
iPTMneti | O89017 |
MetOSitei | O89017 |
PhosphoSitePlusi | O89017 |
SwissPalmi | O89017 |
Expressioni
Tissue specificityi
Detected in kidney proximal tubules (at protein level). Ubiquitous. Particularly abundant in kidney and placenta.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000021190, Expressed in ileum and 312 other tissues |
ExpressionAtlasi | O89017, baseline and differential |
Genevisiblei | O89017, MM |
Interactioni
Subunit structurei
May interact with integrins (By similarity). Monomer after autocatalytic processing. Homodimer before autocatalytic removal of the propeptide.
By similarity1 PublicationProtein-protein interaction databases
BioGRIDi | 202402, 7 interactors |
IntActi | O89017, 2 interactors |
MINTi | O89017 |
STRINGi | 10090.ENSMUSP00000021607 |
Chemistry databases
BindingDBi | O89017 |
Miscellaneous databases
RNActi | O89017, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O89017 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
In the zymogen form, the uncleaved propeptide blocks access to the active site.By similarity
Sequence similaritiesi
Belongs to the peptidase C13 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG1348, Eukaryota |
GeneTreei | ENSGT00940000154782 |
HOGENOMi | CLU_024160_2_0_1 |
InParanoidi | O89017 |
OMAi | IRYMYEH |
OrthoDBi | 826971at2759 |
PhylomeDBi | O89017 |
TreeFami | TF313403 |
Family and domain databases
InterProi | View protein in InterPro IPR043577, AE IPR001096, Peptidase_C13 |
PANTHERi | PTHR12000, PTHR12000, 1 hit |
Pfami | View protein in Pfam PF01650, Peptidase_C13, 1 hit |
PIRSFi | PIRSF500139, AE, 1 hit PIRSF019663, Legumain, 1 hit |
PRINTSi | PR00776, HEMOGLOBNASE |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
O89017-1 [UniParc]FASTAAdd to basket
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
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ000990 mRNA Translation: CAA04439.1 AF044266 mRNA Translation: AAF21659.1 |
CCDSi | CCDS26119.1 |
RefSeqi | NP_035305.1, NM_011175.3 |
Genome annotation databases
Ensembli | ENSMUST00000021607; ENSMUSP00000021607; ENSMUSG00000021190 ENSMUST00000110020; ENSMUSP00000105647; ENSMUSG00000021190 |
GeneIDi | 19141 |
KEGGi | mmu:19141 |
UCSCi | uc007oue.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ000990 mRNA Translation: CAA04439.1 AF044266 mRNA Translation: AAF21659.1 |
CCDSi | CCDS26119.1 |
RefSeqi | NP_035305.1, NM_011175.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4NOJ | X-ray | 2.80 | A | 27-289 | [»] | |
4NOK | X-ray | 2.50 | A | 1-435 | [»] | |
4NOL | X-ray | 2.70 | A/B | 1-435 | [»] | |
4NOM | X-ray | 2.01 | A | 1-435 | [»] | |
SMRi | O89017 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 202402, 7 interactors |
IntActi | O89017, 2 interactors |
MINTi | O89017 |
STRINGi | 10090.ENSMUSP00000021607 |
Chemistry databases
BindingDBi | O89017 |
ChEMBLi | CHEMBL1949492 |
Protein family/group databases
MEROPSi | C13.004 |
PTM databases
GlyConnecti | 2463, 1 N-Linked glycan (1 site) |
GlyGeni | O89017, 4 sites |
iPTMneti | O89017 |
MetOSitei | O89017 |
PhosphoSitePlusi | O89017 |
SwissPalmi | O89017 |
Proteomic databases
EPDi | O89017 |
jPOSTi | O89017 |
MaxQBi | O89017 |
PaxDbi | O89017 |
PeptideAtlasi | O89017 |
PRIDEi | O89017 |
Protocols and materials databases
Antibodypediai | 17, 307 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000021607; ENSMUSP00000021607; ENSMUSG00000021190 ENSMUST00000110020; ENSMUSP00000105647; ENSMUSG00000021190 |
GeneIDi | 19141 |
KEGGi | mmu:19141 |
UCSCi | uc007oue.1, mouse |
Organism-specific databases
CTDi | 5641 |
MGIi | MGI:1330838, Lgmn |
Phylogenomic databases
eggNOGi | KOG1348, Eukaryota |
GeneTreei | ENSGT00940000154782 |
HOGENOMi | CLU_024160_2_0_1 |
InParanoidi | O89017 |
OMAi | IRYMYEH |
OrthoDBi | 826971at2759 |
PhylomeDBi | O89017 |
TreeFami | TF313403 |
Enzyme and pathway databases
BRENDAi | 3.4.22.34, 3474 |
Reactomei | R-MMU-1679131, Trafficking and processing of endosomal TLR R-MMU-2132295, MHC class II antigen presentation |
Miscellaneous databases
BioGRID-ORCSi | 19141, 1 hit in 17 CRISPR screens |
ChiTaRSi | Lgmn, mouse |
PROi | PR:O89017 |
RNActi | O89017, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000021190, Expressed in ileum and 312 other tissues |
ExpressionAtlasi | O89017, baseline and differential |
Genevisiblei | O89017, MM |
Family and domain databases
InterProi | View protein in InterPro IPR043577, AE IPR001096, Peptidase_C13 |
PANTHERi | PTHR12000, PTHR12000, 1 hit |
Pfami | View protein in Pfam PF01650, Peptidase_C13, 1 hit |
PIRSFi | PIRSF500139, AE, 1 hit PIRSF019663, Legumain, 1 hit |
PRINTSi | PR00776, HEMOGLOBNASE |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LGMN_MOUSE | |
Accessioni | O89017Primary (citable) accession number: O89017 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 24, 2002 |
Last sequence update: | November 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 153 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Peptidase families
Classification of peptidase families and list of entries