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Protein

Legumain

Gene

LGMN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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 (By similarity). May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system.By similarity1 Publication

Catalytic activityi

Hydrolysis of proteins and small molecule substrates at -Asn-|-Xaa- bonds.1 Publication

pH dependencei

Optimum pH is 5.5 for the free enzyme, and pH 6 in the presence of bound integrins.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1481 Publication1
Active sitei189Nucleophile1 Publication1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: ARUK-UCL
  • peptidase activity Source: MGI

GO - Biological processi

  • activation of cysteine-type endopeptidase activity Source: ARUK-UCL
  • antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
  • associative learning Source: ARUK-UCL
  • cellular response to amyloid-beta Source: ARUK-UCL
  • cellular response to calcium ion Source: ARUK-UCL
  • cellular response to hepatocyte growth factor stimulus Source: ARUK-UCL
  • dendritic spine organization Source: ARUK-UCL
  • memory Source: ARUK-UCL
  • negative regulation of ERBB signaling pathway Source: UniProtKB
  • negative regulation of gene expression Source: ARUK-UCL
  • negative regulation of multicellular organism growth Source: Ensembl
  • negative regulation of neuron apoptotic process Source: MGI
  • positive regulation of cell proliferation Source: ARUK-UCL
  • positive regulation of endothelial cell chemotaxis Source: ARUK-UCL
  • positive regulation of long-term synaptic potentiation Source: ARUK-UCL
  • positive regulation of mitotic cell cycle Source: ARUK-UCL
  • positive regulation of monocyte chemotaxis Source: ARUK-UCL
  • 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: ARUK-UCL
  • vacuolar protein processing Source: GO_Central
  • vitamin D metabolic process Source: Reactome

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease

Enzyme and pathway databases

BRENDAi3.4.22.34 2681
ReactomeiR-HSA-1679131 Trafficking and processing of endosomal TLR
R-HSA-196791 Vitamin D (calciferol) metabolism
R-HSA-2132295 MHC class II antigen presentation
SABIO-RKiQ99538

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100600.14
HGNCiHGNC:9472 LGMN
MIMi602620 gene
neXtProtiNX_Q99538

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi190E → K: Increases catalytic activity at pH 5.5. 1 Publication1
Mutagenesisi323N → D, Q or S: Loss of autoactivation. 1

Organism-specific databases

DisGeNETi5641
OpenTargetsiENSG00000100600
PharmGKBiPA30354

Chemistry databases

ChEMBLiCHEMBL4244
GuidetoPHARMACOLOGYi2380

Polymorphism and mutation databases

BioMutaiLGMN
DMDMi2842759

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 171 PublicationAdd BLAST17
ChainiPRO_000002650218 – 323LegumainAdd BLAST306
PropeptideiPRO_0000026503324 – 433Add BLAST110

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi91N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi167N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi263N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi272N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi378 ↔ 412By similarity
Disulfide bondi390 ↔ 429By similarity

Post-translational modificationi

Glycosylated.2 Publications
Activated by autocatalytic processing at pH 4.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei323 – 324Cleavage; by autolysis2

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiQ99538
MaxQBiQ99538
PaxDbiQ99538
PeptideAtlasiQ99538
PRIDEiQ99538
ProteomicsDBi78313

PTM databases

iPTMnetiQ99538
PhosphoSitePlusiQ99538

Miscellaneous databases

PMAP-CutDBiQ99538

Expressioni

Tissue specificityi

Ubiquitous. Particularly abundant in kidney, heart and placenta.

Gene expression databases

BgeeiENSG00000100600
CleanExiHS_LGMN
ExpressionAtlasiQ99538 baseline and differential
GenevisibleiQ99538 HS

Organism-specific databases

HPAiHPA001426

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi111624, 19 interactors
IntActiQ99538, 10 interactors
STRINGi9606.ENSP00000334052

Chemistry databases

BindingDBiQ99538

Structurei

Secondary structure

1433
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 35Combined sources8
Helixi40 – 42Combined sources3
Helixi43 – 58Combined sources16
Helixi63 – 65Combined sources3
Beta strandi66 – 69Combined sources4
Beta strandi87 – 89Combined sources3
Helixi105 – 107Combined sources3
Helixi110 – 118Combined sources9
Turni121 – 126Combined sources6
Beta strandi140 – 146Combined sources7
Beta strandi153 – 155Combined sources3
Beta strandi157 – 162Combined sources6
Helixi163 – 175Combined sources13
Beta strandi180 – 186Combined sources7
Helixi191 – 194Combined sources4
Turni195 – 197Combined sources3
Beta strandi202 – 210Combined sources9
Beta strandi217 – 222Combined sources6
Turni223 – 226Combined sources4
Beta strandi227 – 231Combined sources5
Helixi232 – 243Combined sources12
Turni246 – 248Combined sources3
Helixi251 – 261Combined sources11
Beta strandi268 – 271Combined sources4
Helixi273 – 277Combined sources5
Helixi281 – 284Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4AW9X-ray2.20A26-309[»]
4AWAX-ray2.50A26-309[»]
4AWBX-ray2.70A/B26-309[»]
4FGUX-ray3.90A/B18-433[»]
4N6NX-ray1.87A26-303[»]
4N6OX-ray1.80A26-303[»]
5LU8X-ray1.95A26-288[»]
5LU9X-ray2.27A26-288[»]
5LUAX-ray2.00A/B26-287[»]
5LUBX-ray2.10A/B26-287[»]
ProteinModelPortaliQ99538
SMRiQ99538
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

In the zymogen form, the uncleaved propeptide blocks access to the active site.1 Publication

Sequence similaritiesi

Belongs to the peptidase C13 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1348 Eukaryota
COG5206 LUCA
GeneTreeiENSGT00530000063391
HOGENOMiHOG000236335
HOVERGENiHBG031304
InParanoidiQ99538
KOiK01369
OMAiKVMQFQG
OrthoDBiEOG091G08C5
PhylomeDBiQ99538
TreeFamiTF313403

Family and domain databases

InterProiView protein in InterPro
IPR001096 Peptidase_C13
PANTHERiPTHR12000 PTHR12000, 1 hit
PfamiView protein in Pfam
PF01650 Peptidase_C13, 1 hit
PIRSFiPIRSF019663 Legumain, 1 hit
PRINTSiPR00776 HEMOGLOBNASE

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99538-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVWKVAVFLS VALGIGAVPI DDPEDGGKHW VVIVAGSNGW YNYRHQADAC
60 70 80 90 100
HAYQIIHRNG IPDEQIVVMM YDDIAYSEDN PTPGIVINRP NGTDVYQGVP
110 120 130 140 150
KDYTGEDVTP QNFLAVLRGD AEAVKGIGSG KVLKSGPQDH VFIYFTDHGS
160 170 180 190 200
TGILVFPNED LHVKDLNETI HYMYKHKMYR KMVFYIEACE SGSMMNHLPD
210 220 230 240 250
NINVYATTAA NPRESSYACY YDEKRSTYLG DWYSVNWMED SDVEDLTKET
260 270 280 290 300
LHKQYHLVKS HTNTSHVMQY GNKTISTMKV MQFQGMKRKA SSPVPLPPVT
310 320 330 340 350
HLDLTPSPDV PLTIMKRKLM NTNDLEESRQ LTEEIQRHLD ARHLIEKSVR
360 370 380 390 400
KIVSLLAASE AEVEQLLSER APLTGHSCYP EALLHFRTHC FNWHSPTYEY
410 420 430
ALRHLYVLVN LCEKPYPLHR IKLSMDHVCL GHY
Length:433
Mass (Da):49,411
Last modified:May 1, 1997 - v1
Checksum:i081AD2D0D584E72A
GO
Isoform 2 (identifier: Q99538-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     341-397: Missing.

Note: No experimental confirmation available.
Show »
Length:376
Mass (Da):42,948
Checksum:i582E0D702B640C1F
GO
Isoform 3 (identifier: Q99538-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     341-372: ARHLIEKSVRKIVSLLAASEAEVEQLLSERAP → DKIVHGPRVPWSLLKSCLLEAFPSVSAPPTVC
     373-433: Missing.

Note: No experimental confirmation available.
Show »
Length:372
Mass (Da):42,008
Checksum:i915FFBB4216E8BF6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31V → A in BAA09530 (PubMed:8893817).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02458818V → I1 PublicationCorresponds to variant dbSNP:rs2236264Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056454341 – 397Missing in isoform 2. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_056455341 – 372ARHLI…SERAP → DKIVHGPRVPWSLLKSCLLE AFPSVSAPPTVC in isoform 3. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_056456373 – 433Missing in isoform 3. 1 PublicationAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09862 mRNA Translation: CAA70989.1
D55696 mRNA Translation: BAA09530.1
BX161380 mRNA Translation: CAD61872.1
BX161422 mRNA Translation: CAD61895.1
AL132987 Genomic DNA No translation available.
AL136332 Genomic DNA No translation available.
BC003061 mRNA Translation: AAH03061.1
CCDSiCCDS9904.1 [Q99538-1]
RefSeqiNP_001008530.1, NM_001008530.2 [Q99538-1]
NP_005597.3, NM_005606.6 [Q99538-1]
XP_005267919.1, XM_005267862.3 [Q99538-2]
XP_005267920.1, XM_005267863.3 [Q99538-3]
XP_016876952.1, XM_017021463.1 [Q99538-1]
XP_016876953.1, XM_017021464.1 [Q99538-1]
XP_016876954.1, XM_017021465.1 [Q99538-1]
XP_016876955.1, XM_017021466.1 [Q99538-2]
XP_016876956.1, XM_017021467.1 [Q99538-3]
UniGeneiHs.18069

Genome annotation databases

EnsembliENST00000334869; ENSP00000334052; ENSG00000100600 [Q99538-1]
ENST00000393218; ENSP00000376911; ENSG00000100600 [Q99538-1]
ENST00000555699; ENSP00000451861; ENSG00000100600 [Q99538-3]
ENST00000557434; ENSP00000452572; ENSG00000100600 [Q99538-2]
GeneIDi5641
KEGGihsa:5641
UCSCiuc001yav.4 human [Q99538-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLGMN_HUMAN
AccessioniPrimary (citable) accession number: Q99538
Secondary accession number(s): O00123
, Q86TV2, Q86TV3, Q9BTY1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: June 20, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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