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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)DescriptionActionsGraphical viewLength
Active sitei1501 Publication1
Active sitei191Nucleophile1 Publication1

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
  • vacuolar protein processing Source: GO_Central
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)DescriptionActionsGraphical viewLength
Mutagenesisi44N → A: Nearly abolishes enzyme activity. 1 Publication1
Mutagenesisi46R → A: Nearly abolishes enzyme activity. 1 Publication1
Mutagenesisi47H → A: 54% Loss of activity. 1 Publication1
Mutagenesisi52C → S: No loss of activity. 1 Publication1
Mutagenesisi150H → A: Complete loss of activity. Abolishes autocatalytic processing. 2 Publications1
Mutagenesisi189E → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi191C → A or S: Abolishes enzyme activity. 2 Publications1
Mutagenesisi233D → A: Abolishes enzyme activity. Abolishes autocatalytic processing. 1 Publication1
Mutagenesisi311D → A: Nearly abolishes enzyme activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1949492.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17By similarityAdd BLAST17
ChainiPRO_000002650418 – 325LegumainAdd BLAST308
PropeptideiPRO_0000026505326 – 435Add BLAST110

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi93N-linked (GlcNAc...)Sequence analysis1
Glycosylationi169N-linked (GlcNAc...)Sequence analysis1
Glycosylationi265N-linked (GlcNAc...)Sequence analysis1
Glycosylationi274N-linked (GlcNAc...)Sequence analysis1
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)DescriptionActionsGraphical viewLength
Sitei325 – 326Cleavage; by autolysis2

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiO89017.
MaxQBiO89017.
PaxDbiO89017.
PeptideAtlasiO89017.
PRIDEiO89017.

PTM databases

iPTMnetiO89017.
PhosphoSitePlusiO89017.
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

BgeeiENSMUSG00000021190.
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 interactor.
IntActiO89017. 2 interactors.
MINTiMINT-4100371.
STRINGi10090.ENSMUSP00000021607.

Chemistry databases

BindingDBiO89017.

Structurei

Secondary structure

1435
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi31 – 37Combined sources7
Helixi42 – 44Combined sources3
Helixi45 – 60Combined sources16
Helixi65 – 67Combined sources3
Beta strandi68 – 71Combined sources4
Beta strandi76 – 79Combined sources4
Beta strandi89 – 91Combined sources3
Helixi107 – 109Combined sources3
Helixi112 – 120Combined sources9
Helixi124 – 126Combined sources3
Beta strandi142 – 149Combined sources8
Beta strandi155 – 157Combined sources3
Beta strandi159 – 164Combined sources6
Helixi165 – 177Combined sources13
Beta strandi182 – 190Combined sources9
Helixi193 – 196Combined sources4
Turni197 – 199Combined sources3
Beta strandi202 – 212Combined sources11
Beta strandi219 – 224Combined sources6
Turni225 – 228Combined sources4
Beta strandi229 – 233Combined sources5
Helixi234 – 245Combined sources12
Turni248 – 250Combined sources3
Helixi253 – 263Combined sources11
Beta strandi270 – 273Combined sources4
Helixi275 – 279Combined sources5
Helixi283 – 286Combined sources4
Helixi309 – 311Combined sources3
Helixi312 – 323Combined sources12
Helixi327 – 359Combined sources33
Helixi363 – 370Combined sources8
Helixi378 – 391Combined sources14
Helixi401 – 406Combined sources6
Helixi407 – 415Combined sources9
Helixi420 – 431Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NOJX-ray2.80A27-289[»]
4NOKX-ray2.50A1-435[»]
4NOLX-ray2.70A/B1-435[»]
4NOMX-ray2.01A1-435[»]
ProteinModelPortaliO89017.
SMRiO89017.
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.
OMAiDRIKLSM.
OrthoDBiEOG091G08C5.
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_011175.3.
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_011175.3.
UniGeneiMm.17185.

3D structure databases

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

Protein-protein interaction databases

BioGridi202402. 1 interactor.
IntActiO89017. 2 interactors.
MINTiMINT-4100371.
STRINGi10090.ENSMUSP00000021607.

Chemistry databases

BindingDBiO89017.
ChEMBLiCHEMBL1949492.

Protein family/group databases

MEROPSiC13.004.

PTM databases

iPTMnetiO89017.
PhosphoSitePlusiO89017.
SwissPalmiO89017.

Proteomic databases

EPDiO89017.
MaxQBiO89017.
PaxDbiO89017.
PeptideAtlasiO89017.
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.
OMAiDRIKLSM.
OrthoDBiEOG091G08C5.
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

BgeeiENSMUSG00000021190.
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...

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: November 2, 2016
This is version 130 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.