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Protein

Legumain

Gene

LGMN

Organism
Homo sapiens (Human)
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. 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: UniProtKB
  • peptidase activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Enzyme and pathway databases

BioCyciZFISH:HS02119-MONOMER.
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-RKQ99538.

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

HGNCiHGNC:9472. LGMN.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • late endosome Source: Ensembl
  • lysosomal lumen Source: Reactome
  • lysosome Source: UniProtKB
Complete GO annotation...

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...)2 Publications1
Glycosylationi167N-linked (GlcNAc...)2 Publications1
Glycosylationi263N-linked (GlcNAc...)1 Publication1
Glycosylationi272N-linked (GlcNAc...)1 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.

PTM databases

iPTMnetiQ99538.
PhosphoSitePlusiQ99538.

Miscellaneous databases

PMAP-CutDBQ99538.

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

HPAiHPA000799.
HPA001426.

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. 18 interactors.
IntActiQ99538. 9 interactors.
MINTiMINT-4537529.
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[»]
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.
OMAiDRIKLSM.
OrthoDBiEOG091G08C5.
PhylomeDBiQ99538.
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.

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 → I.1 PublicationCorresponds to variant rs2236264dbSNPEnsembl.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

Cross-referencesi

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.

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[»]
ProteinModelPortaliQ99538.
SMRiQ99538.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111624. 18 interactors.
IntActiQ99538. 9 interactors.
MINTiMINT-4537529.
STRINGi9606.ENSP00000334052.

Chemistry databases

BindingDBiQ99538.
ChEMBLiCHEMBL4244.
GuidetoPHARMACOLOGYi2380.

Protein family/group databases

MEROPSiC13.004.

PTM databases

iPTMnetiQ99538.
PhosphoSitePlusiQ99538.

Polymorphism and mutation databases

BioMutaiLGMN.
DMDMi2842759.

Proteomic databases

EPDiQ99538.
MaxQBiQ99538.
PaxDbiQ99538.
PeptideAtlasiQ99538.
PRIDEiQ99538.

Protocols and materials databases

DNASUi5641.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi5641.
DisGeNETi5641.
GeneCardsiLGMN.
HGNCiHGNC:9472. LGMN.
HPAiHPA000799.
HPA001426.
MIMi602620. gene.
neXtProtiNX_Q99538.
OpenTargetsiENSG00000100600.
PharmGKBiPA30354.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS02119-MONOMER.
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-RKQ99538.

Miscellaneous databases

ChiTaRSiLGMN. human.
GeneWikiiLGMN.
GenomeRNAii5641.
PMAP-CutDBQ99538.
PROiQ99538.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100600.
CleanExiHS_LGMN.
ExpressionAtlasiQ99538. baseline and differential.
GenevisibleiQ99538. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q99538
Secondary accession number(s): O00123
, Q86TV2, Q86TV3, Q9BTY1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: November 2, 2016
This is version 157 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.