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Q99538 (LGMN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Legumain

EC=3.4.22.34
Alternative name(s):
Asparaginyl endopeptidase
Protease, cysteine 1
Gene names
Name:LGMN
Synonyms:PRSC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length433 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8

Catalytic activity

Hydrolysis of proteins and small molecule substrates at -Asn-|-Xaa- bonds. Ref.8

Subunit structure

Monomer. May interact with integrins. Ref.8

Subcellular location

Lysosome By similarity.

Tissue specificity

Ubiquitous. Particularly abundant in kidney, heart and placenta.

Domain

In the zymogen form, the uncleaved propeptide blocks access to the active site. Ref.8

Post-translational modification

Glycosylated.

Activated by autocatalytic processing at pH 4.

Sequence similarities

Belongs to the peptidase C13 family.

Biophysicochemical properties

pH dependence:

Optimum pH is 5.5 for the free enzyme, and pH 6 in the presence of bound integrins. Ref.8

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Thiol protease
   PTMGlycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

negative regulation of ERBB signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from genetic interaction PubMed 18374643. Source: MGI

proteolysis

Inferred from sequence or structural similarity Ref.1. Source: UniProtKB

proteolysis involved in cellular protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

receptor catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

renal system process

Inferred from sequence or structural similarity. Source: UniProtKB

response to acid

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

vitamin D metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentapical part of cell

Inferred from electronic annotation. Source: Ensembl

late endosome

Inferred from electronic annotation. Source: Ensembl

lysosomal lumen

Traceable author statement. Source: Reactome

lysosome

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncysteine-type endopeptidase activity

Inferred from sequence or structural similarity Ref.1. Source: UniProtKB

peptidase activity

Inferred from direct assay PubMed 136644. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Ref.4
Chain18 – 323306Legumain
PRO_0000026502
Propeptide324 – 433110
PRO_0000026503

Sites

Active site1481 Probable
Active site1891Nucleophile Ref.8
Site323 – 3242Cleavage; by autolysis

Amino acid modifications

Glycosylation911N-linked (GlcNAc...) Ref.6
Glycosylation1671N-linked (GlcNAc...) Ref.6
Glycosylation2631N-linked (GlcNAc...) Potential
Glycosylation2721N-linked (GlcNAc...) Potential

Natural variations

Natural variant181V → I. Ref.3
Corresponds to variant rs2236264 [ dbSNP | Ensembl ].
VAR_024588

Experimental info

Mutagenesis1901E → K: Increases catalytic activity at pH 5.5. Ref.8
Mutagenesis3231N → D, Q or S: Loss of autoactivation.
Sequence conflict311V → A in BAA09530. Ref.2

Secondary structure

.............................................. 433
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q99538 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 081AD2D0D584E72A

FASTA43349,411
        10         20         30         40         50         60 
MVWKVAVFLS VALGIGAVPI DDPEDGGKHW VVIVAGSNGW YNYRHQADAC HAYQIIHRNG 

        70         80         90        100        110        120 
IPDEQIVVMM YDDIAYSEDN PTPGIVINRP NGTDVYQGVP KDYTGEDVTP QNFLAVLRGD 

       130        140        150        160        170        180 
AEAVKGIGSG KVLKSGPQDH VFIYFTDHGS TGILVFPNED LHVKDLNETI HYMYKHKMYR 

       190        200        210        220        230        240 
KMVFYIEACE SGSMMNHLPD NINVYATTAA NPRESSYACY YDEKRSTYLG DWYSVNWMED 

       250        260        270        280        290        300 
SDVEDLTKET LHKQYHLVKS HTNTSHVMQY GNKTISTMKV MQFQGMKRKA SSPVPLPPVT 

       310        320        330        340        350        360 
HLDLTPSPDV PLTIMKRKLM NTNDLEESRQ LTEEIQRHLD ARHLIEKSVR KIVSLLAASE 

       370        380        390        400        410        420 
AEVEQLLSER APLTGHSCYP EALLHFRTHC FNWHSPTYEY ALRHLYVLVN LCEKPYPLHR 

       430 
IKLSMDHVCL GHY 

« Hide

References

« Hide 'large scale' references
[1]"Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase."
Chen J.-M., Dando P.M., Rawlings N.D., Brown M.A., Young N.E., Stevens R.A.E., Hewitt E., Watts C., Barrett A.J.
J. Biol. Chem. 272:8090-8098(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"Molecular cloning of a human cDNA encoding putative cysteine protease (PRSC1) and its chromosome assignment to 14q32.1."
Tanaka T., Inazawa J., Nakamura Y.
Cytogenet. Cell Genet. 74:120-123(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-18.
Tissue: Placenta.
[4]"Activation of human prolegumain by cleavage at a C-terminal asparagine residue."
Chen J.-M., Fortunato M., Barrett A.J.
Biochem. J. 352:327-334(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-24 AND 324-330, PROTEOLYTIC PROCESSING.
[5]"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: CHARACTERIZATION OF ACTIVITY ON ASPARTATE BONDS, AUTOCATALYTIC CLEAVAGE.
[6]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-91 AND ASN-167.
Tissue: Liver.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Mechanistic and structural studies on legumain explain its zymogenicity, distinct activation pathways, and regulation."
Dall E., Brandstetter H.
Proc. Natl. Acad. Sci. U.S.A. 110:10940-10945(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 26-309, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, PROPEPTIDE, SUBUNIT, DOMAIN, MUTAGENESIS OF GLU-190, AUTOCATALYTIC PROCESSING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y09862 mRNA. Translation: CAA70989.1.
D55696 mRNA. Translation: BAA09530.1.
BC003061 mRNA. Translation: AAH03061.1.
RefSeqNP_001008530.1. NM_001008530.2.
NP_005597.3. NM_005606.6.
UniGeneHs.18069.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4AW9X-ray2.20A26-309[»]
4AWAX-ray2.50A26-309[»]
4AWBX-ray2.70A/B26-309[»]
4FGUX-ray3.90A/B19-433[»]
ProteinModelPortalQ99538.
SMRQ99538. Positions 28-433.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111624. 8 interactions.
IntActQ99538. 4 interactions.
MINTMINT-4537529.
STRING9606.ENSP00000334052.

Chemistry

BindingDBQ99538.
ChEMBLCHEMBL4244.

Protein family/group databases

MEROPSC13.004.

PTM databases

PhosphoSiteQ99538.

Polymorphism databases

DMDM2842759.

Proteomic databases

PaxDbQ99538.
PRIDEQ99538.

Protocols and materials databases

DNASU5641.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334869; ENSP00000334052; ENSG00000100600.
ENST00000393218; ENSP00000376911; ENSG00000100600.
GeneID5641.
KEGGhsa:5641.
UCSCuc001yav.3. human.

Organism-specific databases

CTD5641.
GeneCardsGC14M093170.
HGNCHGNC:9472. LGMN.
HPAHPA000799.
HPA001426.
MIM602620. gene.
neXtProtNX_Q99538.
PharmGKBPA30354.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5206.
HOGENOMHOG000236335.
HOVERGENHBG031304.
InParanoidQ99538.
KOK01369.
OMAKVMQFQG.
PhylomeDBQ99538.
TreeFamTF313403.

Enzyme and pathway databases

BRENDA3.4.22.34. 2681.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
REACT_6900. Immune System.
SABIO-RKQ99538.

Gene expression databases

ArrayExpressQ99538.
BgeeQ99538.
CleanExHS_LGMN.
GenevestigatorQ99538.

Family and domain databases

InterProIPR001096. Peptidase_C13.
[Graphical view]
PANTHERPTHR12000. PTHR12000. 1 hit.
PfamPF01650. Peptidase_C13. 1 hit.
[Graphical view]
PIRSFPIRSF019663. Legumain. 1 hit.
PRINTSPR00776. HEMOGLOBNASE.
ProtoNetSearch...

Other

ChiTaRSLGMN. human.
GeneWikiLGMN.
GenomeRNAi5641.
NextBio21918.
PMAP-CutDBQ99538.
PROQ99538.
SOURCESearch...

Entry information

Entry nameLGMN_HUMAN
AccessionPrimary (citable) accession number: Q99538
Secondary accession number(s): O00123, Q9BTY1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM