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Protein

Legumain

Gene

Lgmn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Enzyme regulationi

Inhibited by cystatin-C.1 Publication

pH dependencei

Optimum pH is 6.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei150 – 15011 Publication
Active sitei191 – 1911Nucleophile1 Publication

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • peptidase activity Source: MGI

GO - Biological processi

  • negative regulation of ERBB signaling pathway Source: UniProtKB
  • negative regulation of multicellular organism growth Source: MGI
  • negative regulation of neuron apoptotic process 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: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Enzyme and pathway databases

BRENDAi3.4.22.34. 3474.
ReactomeiR-MMU-1679131. Trafficking and processing of endosomal TLR.
R-MMU-196791. Vitamin D (calciferol) metabolism.
R-MMU-2132295. MHC class II antigen presentation.

Protein family/group databases

MEROPSiC13.004.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1330838. Lgmn.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: MGI
  • extracellular exosome Source: MGI
  • late endosome Source: MGI
  • lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441N → A: Nearly abolishes enzyme activity. 1 Publication
Mutagenesisi46 – 461R → A: Nearly abolishes enzyme activity. 1 Publication
Mutagenesisi47 – 471H → A: 54% Loss of activity. 1 Publication
Mutagenesisi52 – 521C → S: No loss of activity. 1 Publication
Mutagenesisi150 – 1501H → A: Complete loss of activity. Abolishes autocatalytic processing. 2 Publications
Mutagenesisi189 – 1891E → A: Abolishes enzyme activity. 1 Publication
Mutagenesisi191 – 1911C → A or S: Abolishes enzyme activity. 2 Publications
Mutagenesisi233 – 2331D → A: Abolishes enzyme activity. Abolishes autocatalytic processing. 1 Publication
Mutagenesisi311 – 3111D → A: Nearly abolishes enzyme activity. 1 Publication

Chemistry

ChEMBLiCHEMBL1949492.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717By similarityAdd
BLAST
Chaini18 – 325308LegumainPRO_0000026504Add
BLAST
Propeptidei326 – 435110PRO_0000026505Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi93 – 931N-linked (GlcNAc...)Sequence analysis
Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence analysis
Glycosylationi265 – 2651N-linked (GlcNAc...)Sequence analysis
Glycosylationi274 – 2741N-linked (GlcNAc...)Sequence analysis
Disulfide bondi380 ↔ 4141 Publication
Disulfide bondi392 ↔ 4311 Publication

Post-translational modificationi

Glycosylated.1 Publication
Activated by autocatalytic processing at pH 4.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei325 – 3262Cleavage; by autolysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiO89017.
MaxQBiO89017.
PaxDbiO89017.
PRIDEiO89017.

PTM databases

iPTMnetiO89017.
PhosphoSiteiO89017.
SwissPalmiO89017.

Miscellaneous databases

PMAP-CutDBO89017.

Expressioni

Tissue specificityi

Detected in kidney proximal tubules (at protein level). Ubiquitous. Particularly abundant in kidney and placenta.2 Publications

Gene expression databases

BgeeiO89017.
CleanExiMM_LGMN.
ExpressionAtlasiO89017. baseline and differential.
GenevisibleiO89017. MM.

Interactioni

Subunit structurei

May interact with integrins (By similarity). Monomer after autocatalytic processing. Homodimer before autocatalytic removal of the propeptide.By similarity1 Publication

Protein-protein interaction databases

BioGridi202402. 1 interaction.
IntActiO89017. 2 interactions.
MINTiMINT-4100371.
STRINGi10090.ENSMUSP00000021607.

Chemistry

BindingDBiO89017.

Structurei

Secondary structure

1
435
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi31 – 377Combined sources
Helixi42 – 443Combined sources
Helixi45 – 6016Combined sources
Helixi65 – 673Combined sources
Beta strandi68 – 714Combined sources
Beta strandi76 – 794Combined sources
Beta strandi89 – 913Combined sources
Helixi107 – 1093Combined sources
Helixi112 – 1209Combined sources
Helixi124 – 1263Combined sources
Beta strandi142 – 1498Combined sources
Beta strandi155 – 1573Combined sources
Beta strandi159 – 1646Combined sources
Helixi165 – 17713Combined sources
Beta strandi182 – 1909Combined sources
Helixi193 – 1964Combined sources
Turni197 – 1993Combined sources
Beta strandi202 – 21211Combined sources
Beta strandi219 – 2246Combined sources
Turni225 – 2284Combined sources
Beta strandi229 – 2335Combined sources
Helixi234 – 24512Combined sources
Turni248 – 2503Combined sources
Helixi253 – 26311Combined sources
Beta strandi270 – 2734Combined sources
Helixi275 – 2795Combined sources
Helixi283 – 2864Combined sources
Helixi309 – 3113Combined sources
Helixi312 – 32312Combined sources
Helixi327 – 35933Combined sources
Helixi363 – 3708Combined sources
Helixi378 – 39114Combined sources
Helixi401 – 4066Combined sources
Helixi407 – 4159Combined sources
Helixi420 – 43112Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4NOJX-ray2.80A27-289[»]
4NOKX-ray2.50A1-435[»]
4NOLX-ray2.70A/B1-435[»]
4NOMX-ray2.01A1-435[»]
ProteinModelPortaliO89017.
SMRiO89017. Positions 26-432.
ModBaseiSearch...
MobiDBiSearch...

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

Signal

Phylogenomic databases

eggNOGiKOG1348. Eukaryota.
COG5206. LUCA.
GeneTreeiENSGT00530000063391.
HOGENOMiHOG000236335.
HOVERGENiHBG031304.
InParanoidiO89017.
KOiK01369.
OMAiPQDHVFV.
OrthoDBiEOG779NXS.
PhylomeDBiO89017.
TreeFamiTF313403.

Family and domain databases

InterProiIPR001096. Peptidase_C13.
[Graphical view]
PANTHERiPTHR12000. PTHR12000. 1 hit.
PfamiPF01650. Peptidase_C13. 1 hit.
[Graphical view]
PIRSFiPIRSF019663. Legumain. 1 hit.
PRINTSiPR00776. HEMOGLOBNASE.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O89017-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:435
Mass (Da):49,373
Last modified:November 1, 1998 - v1
Checksum:iF956B9E10098013D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ000990 mRNA. Translation: CAA04439.1.
AF044266 mRNA. Translation: AAF21659.1.
CCDSiCCDS26119.1.
RefSeqiNP_035305.1. NM_011175.2.
UniGeneiMm.17185.

Genome annotation databases

EnsembliENSMUST00000021607; ENSMUSP00000021607; ENSMUSG00000021190.
ENSMUST00000110020; ENSMUSP00000105647; ENSMUSG00000021190.
GeneIDi19141.
KEGGimmu:19141.
UCSCiuc007oue.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ000990 mRNA. Translation: CAA04439.1.
AF044266 mRNA. Translation: AAF21659.1.
CCDSiCCDS26119.1.
RefSeqiNP_035305.1. NM_011175.2.
UniGeneiMm.17185.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4NOJX-ray2.80A27-289[»]
4NOKX-ray2.50A1-435[»]
4NOLX-ray2.70A/B1-435[»]
4NOMX-ray2.01A1-435[»]
ProteinModelPortaliO89017.
SMRiO89017. Positions 26-432.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202402. 1 interaction.
IntActiO89017. 2 interactions.
MINTiMINT-4100371.
STRINGi10090.ENSMUSP00000021607.

Chemistry

BindingDBiO89017.
ChEMBLiCHEMBL1949492.

Protein family/group databases

MEROPSiC13.004.

PTM databases

iPTMnetiO89017.
PhosphoSiteiO89017.
SwissPalmiO89017.

Proteomic databases

EPDiO89017.
MaxQBiO89017.
PaxDbiO89017.
PRIDEiO89017.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021607; ENSMUSP00000021607; ENSMUSG00000021190.
ENSMUST00000110020; ENSMUSP00000105647; ENSMUSG00000021190.
GeneIDi19141.
KEGGimmu:19141.
UCSCiuc007oue.1. mouse.

Organism-specific databases

CTDi5641.
MGIiMGI:1330838. Lgmn.

Phylogenomic databases

eggNOGiKOG1348. Eukaryota.
COG5206. LUCA.
GeneTreeiENSGT00530000063391.
HOGENOMiHOG000236335.
HOVERGENiHBG031304.
InParanoidiO89017.
KOiK01369.
OMAiPQDHVFV.
OrthoDBiEOG779NXS.
PhylomeDBiO89017.
TreeFamiTF313403.

Enzyme and pathway databases

BRENDAi3.4.22.34. 3474.
ReactomeiR-MMU-1679131. Trafficking and processing of endosomal TLR.
R-MMU-196791. Vitamin D (calciferol) metabolism.
R-MMU-2132295. MHC class II antigen presentation.

Miscellaneous databases

ChiTaRSiLgmn. mouse.
PMAP-CutDBO89017.
PROiO89017.
SOURCEiSearch...

Gene expression databases

BgeeiO89017.
CleanExiMM_LGMN.
ExpressionAtlasiO89017. baseline and differential.
GenevisibleiO89017. MM.

Family and domain databases

InterProiIPR001096. Peptidase_C13.
[Graphical view]
PANTHERiPTHR12000. PTHR12000. 1 hit.
PfamiPF01650. Peptidase_C13. 1 hit.
[Graphical view]
PIRSFiPIRSF019663. Legumain. 1 hit.
PRINTSiPR00776. HEMOGLOBNASE.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
  2. "Autocatalytic activation of human legumain at aspartic acid residues."
    Halfon S., Patel S., Vega F., Zurawski S., Zurawski G.
    FEBS Lett. 438:114-118(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  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.
  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.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  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.
  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, ENZYME REGULATION.

Entry informationi

Entry nameiLGMN_MOUSE
AccessioniPrimary (citable) accession number: O89017
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 24, 2002
Last sequence update: November 1, 1998
Last modified: June 8, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.