O89017 · LGMN_MOUSE
- ProteinLegumain
- GeneLgmn
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids435 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Has a strict specificity for hydrolysis of asparaginyl bonds (PubMed:24407422, PubMed:9742219, PubMed:9891971).
Can also cleave aspartyl bonds slowly, especially under acidic conditions (PubMed:24407422, PubMed:9742219, PubMed:9891971).
Involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system (By similarity).
Also involved in MHC class I antigen presentation in cross-presenting dendritic cells by mediating cleavage and maturation of Perforin-2 (MPEG1), thereby promoting antigen translocation in the cytosol (PubMed:37347855).
Required for normal lysosomal protein degradation in renal proximal tubules (PubMed:17350006, PubMed:21292981).
Required for normal degradation of internalized EGFR (PubMed:21292981).
Plays a role in the regulation of cell proliferation via its role in EGFR degradation (PubMed:21292981).
Can also cleave aspartyl bonds slowly, especially under acidic conditions (PubMed:24407422, PubMed:9742219, PubMed:9891971).
Involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system (By similarity).
Also involved in MHC class I antigen presentation in cross-presenting dendritic cells by mediating cleavage and maturation of Perforin-2 (MPEG1), thereby promoting antigen translocation in the cytosol (PubMed:37347855).
Required for normal lysosomal protein degradation in renal proximal tubules (PubMed:17350006, PubMed:21292981).
Required for normal degradation of internalized EGFR (PubMed:21292981).
Plays a role in the regulation of cell proliferation via its role in EGFR degradation (PubMed:21292981).
Catalytic activity
Activity regulation
Inhibited by cystatin-C.
pH Dependence
Optimum pH is 6.
Features
Showing features for active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 150 | |||||
Sequence: H | ||||||
Active site | 191 | Nucleophile | ||||
Sequence: C | ||||||
Site | 325-326 | Cleavage; by autolysis | ||||
Sequence: ND |
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLegumain
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO89017
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
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.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 44 | Nearly abolishes enzyme activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 46 | Nearly abolishes enzyme activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 47 | 54% Loss of activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 52 | No loss of activity. | ||||
Sequence: C → S | ||||||
Mutagenesis | 150 | Complete loss of activity. Abolishes autocatalytic processing. | ||||
Sequence: H → A | ||||||
Mutagenesis | 189 | Abolishes enzyme activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 191 | Abolishes enzyme activity. | ||||
Sequence: C → A or S | ||||||
Mutagenesis | 233 | Abolishes enzyme activity. Abolishes autocatalytic processing. | ||||
Sequence: D → A | ||||||
Mutagenesis | 311 | Nearly abolishes enzyme activity. | ||||
Sequence: D → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 27 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, glycosylation, propeptide, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-17 | |||||
Sequence: MTWRVAVLLSLVLGAGA | ||||||
Chain | PRO_0000026504 | 18-325 | Legumain | |||
Sequence: VPVGVDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIIVMMYDDIANSEENPTPGVVINRPNGTDVYKGVLKDYTGEDVTPENFLAVLRGDAEAVKGKGSGKVLKSGPRDHVFIYFTDHGATGILVFPNDDLHVKDLNKTIRYMYEHKMYQKMVFYIEACESGSMMNHLPDDINVYATTAANPKESSYACYYDEERGTYLGDWYSVNWMEDSDVEDLTKETLHKQYHLVKSHTNTSHVMQYGNKSISTMKVMQFQGMKHRASSPISLPPVTHLDLTPSPDVPLTILKRKLLRTN | ||||||
Glycosylation | 93 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 169 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 265 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 274 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Propeptide | PRO_0000026505 | 326-435 | ||||
Sequence: DVKESQNLIGQIQQFLDARHVIEKSVHKIVSLLAGFGETAERHLSERTMLTAHDCYQEAVTHFRTHCFNWHSVTYEHALRYLYVLANLCEAPYPIDRIEMAMDKVCLSHY | ||||||
Disulfide bond | 380↔414 | |||||
Sequence: CYQEAVTHFRTHCFNWHSVTYEHALRYLYVLANLC | ||||||
Disulfide bond | 392↔431 | |||||
Sequence: CFNWHSVTYEHALRYLYVLANLCEAPYPIDRIEMAMDKVC |
Post-translational modification
Glycosylated.
Activated by autocatalytic processing at pH 4.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in kidney proximal tubules (at protein level). Ubiquitous. Particularly abundant in kidney and placenta.
Gene expression databases
Structure
Family & Domains
Domain
In the zymogen form, the uncleaved propeptide blocks access to the active site.
Sequence similarities
Belongs to the peptidase C13 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length435
- Mass (Da)49,373
- Last updated1998-11-01 v1
- ChecksumF956B9E10098013D
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ000990 EMBL· GenBank· DDBJ | CAA04439.1 EMBL· GenBank· DDBJ | mRNA | ||
AF044266 EMBL· GenBank· DDBJ | AAF21659.1 EMBL· GenBank· DDBJ | mRNA |