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Q99538

- LGMN_HUMAN

UniProt

Q99538 - LGMN_HUMAN

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Protein
Legumain
Gene
LGMN, PRSC1
Organism
Homo sapiens (Human)
Status
Reviewed - 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.1 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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei148 – 1481 Inferred
Active sitei189 – 1891Nucleophile1 Publication
Sitei323 – 3242Cleavage; by autolysis

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. peptidase activity Source: MGI
Complete GO annotation...

GO - Biological processi

  1. antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
  2. innate immune response Source: Reactome
  3. negative regulation of ERBB signaling pathway Source: UniProtKB
  4. negative regulation of multicellular organism growth Source: Ensembl
  5. negative regulation of neuron apoptotic process Source: MGI
  6. proteolysis Source: UniProtKB
  7. proteolysis involved in cellular protein catabolic process Source: UniProtKB
  8. receptor catabolic process Source: UniProtKB
  9. renal system process Source: UniProtKB
  10. response to acid Source: Ensembl
  11. small molecule metabolic process Source: Reactome
  12. steroid metabolic process Source: Reactome
  13. toll-like receptor signaling pathway Source: Reactome
  14. vitamin D metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Enzyme and pathway databases

BRENDAi3.4.22.34. 2681.
ReactomeiREACT_118632. Trafficking and processing of endosomal TLR.
REACT_121399. MHC class II antigen presentation.
REACT_13523. Vitamin D (calciferol) metabolism.
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
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:9472. LGMN.

Subcellular locationi

Lysosome By similarity

GO - Cellular componenti

  1. apical part of cell Source: Ensembl
  2. late endosome Source: Ensembl
  3. lysosomal lumen Source: Reactome
  4. lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi190 – 1901E → K: Increases catalytic activity at pH 5.5. 1 Publication
Mutagenesisi323 – 3231N → D, Q or S: Loss of autoactivation.

Organism-specific databases

PharmGKBiPA30354.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 17171 Publication
Add
BLAST
Chaini18 – 323306Legumain
PRO_0000026502Add
BLAST
Propeptidei324 – 433110
PRO_0000026503Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi91 – 911N-linked (GlcNAc...)2 Publications
Glycosylationi167 – 1671N-linked (GlcNAc...)2 Publications
Glycosylationi263 – 2631N-linked (GlcNAc...)1 Publication
Glycosylationi272 – 2721N-linked (GlcNAc...)1 Publication
Disulfide bondi378 ↔ 412 By similarity
Disulfide bondi390 ↔ 429 By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ99538.
PaxDbiQ99538.
PRIDEiQ99538.

PTM databases

PhosphoSiteiQ99538.

Miscellaneous databases

PMAP-CutDBQ99538.

Expressioni

Tissue specificityi

Ubiquitous. Particularly abundant in kidney, heart and placenta.

Gene expression databases

ArrayExpressiQ99538.
BgeeiQ99538.
CleanExiHS_LGMN.
GenevestigatoriQ99538.

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.1 Publication

Protein-protein interaction databases

BioGridi111624. 11 interactions.
IntActiQ99538. 4 interactions.
MINTiMINT-4537529.
STRINGi9606.ENSP00000334052.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi28 – 358
Helixi40 – 423
Helixi43 – 5816
Helixi63 – 653
Beta strandi66 – 694
Beta strandi87 – 893
Helixi105 – 1073
Helixi110 – 1189
Helixi122 – 1243
Beta strandi140 – 1478
Beta strandi153 – 1553
Beta strandi157 – 1626
Helixi163 – 17513
Beta strandi180 – 1889
Helixi191 – 1944
Turni195 – 1973
Beta strandi202 – 2109
Beta strandi217 – 2226
Turni223 – 2264
Beta strandi227 – 2315
Helixi232 – 24312
Turni246 – 2483
Helixi251 – 26111
Beta strandi268 – 2714
Helixi273 – 2775
Helixi281 – 2844

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4AW9X-ray2.20A26-309[»]
4AWAX-ray2.50A26-309[»]
4AWBX-ray2.70A/B26-309[»]
4FGUX-ray3.90A/B18-433[»]
ProteinModelPortaliQ99538.
SMRiQ99538. Positions 28-433.

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.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG5206.
HOGENOMiHOG000236335.
HOVERGENiHBG031304.
InParanoidiQ99538.
KOiK01369.
OMAiKVMQFQG.
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.

Sequencei

Sequence statusi: Complete.

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

Q99538-1 [UniParc]FASTAAdd to Basket

« Hide

MVWKVAVFLS VALGIGAVPI DDPEDGGKHW VVIVAGSNGW YNYRHQADAC    50
HAYQIIHRNG IPDEQIVVMM YDDIAYSEDN PTPGIVINRP NGTDVYQGVP 100
KDYTGEDVTP QNFLAVLRGD AEAVKGIGSG KVLKSGPQDH VFIYFTDHGS 150
TGILVFPNED LHVKDLNETI HYMYKHKMYR KMVFYIEACE SGSMMNHLPD 200
NINVYATTAA NPRESSYACY YDEKRSTYLG DWYSVNWMED SDVEDLTKET 250
LHKQYHLVKS HTNTSHVMQY GNKTISTMKV MQFQGMKRKA SSPVPLPPVT 300
HLDLTPSPDV PLTIMKRKLM NTNDLEESRQ LTEEIQRHLD ARHLIEKSVR 350
KIVSLLAASE AEVEQLLSER APLTGHSCYP EALLHFRTHC FNWHSPTYEY 400
ALRHLYVLVN LCEKPYPLHR IKLSMDHVCL GHY 433
Length:433
Mass (Da):49,411
Last modified:May 1, 1997 - v1
Checksum:i081AD2D0D584E72A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181V → I.1 Publication
Corresponds to variant rs2236264 [ dbSNP | Ensembl ].
VAR_024588

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti31 – 311V → A in BAA09530. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y09862 mRNA. Translation: CAA70989.1.
D55696 mRNA. Translation: BAA09530.1.
BC003061 mRNA. Translation: AAH03061.1.
CCDSiCCDS9904.1.
RefSeqiNP_001008530.1. NM_001008530.2.
NP_005597.3. NM_005606.6.
UniGeneiHs.18069.

Genome annotation databases

EnsembliENST00000334869; ENSP00000334052; ENSG00000100600.
ENST00000393218; ENSP00000376911; ENSG00000100600.
GeneIDi5641.
KEGGihsa:5641.
UCSCiuc001yav.3. human.

Polymorphism databases

DMDMi2842759.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y09862 mRNA. Translation: CAA70989.1 .
D55696 mRNA. Translation: BAA09530.1 .
BC003061 mRNA. Translation: AAH03061.1 .
CCDSi CCDS9904.1.
RefSeqi NP_001008530.1. NM_001008530.2.
NP_005597.3. NM_005606.6.
UniGenei Hs.18069.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4AW9 X-ray 2.20 A 26-309 [» ]
4AWA X-ray 2.50 A 26-309 [» ]
4AWB X-ray 2.70 A/B 26-309 [» ]
4FGU X-ray 3.90 A/B 18-433 [» ]
ProteinModelPortali Q99538.
SMRi Q99538. Positions 28-433.
ModBasei Search...

Protein-protein interaction databases

BioGridi 111624. 11 interactions.
IntActi Q99538. 4 interactions.
MINTi MINT-4537529.
STRINGi 9606.ENSP00000334052.

Chemistry

BindingDBi Q99538.
ChEMBLi CHEMBL4244.

Protein family/group databases

MEROPSi C13.004.

PTM databases

PhosphoSitei Q99538.

Polymorphism databases

DMDMi 2842759.

Proteomic databases

MaxQBi Q99538.
PaxDbi Q99538.
PRIDEi Q99538.

Protocols and materials databases

DNASUi 5641.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000334869 ; ENSP00000334052 ; ENSG00000100600 .
ENST00000393218 ; ENSP00000376911 ; ENSG00000100600 .
GeneIDi 5641.
KEGGi hsa:5641.
UCSCi uc001yav.3. human.

Organism-specific databases

CTDi 5641.
GeneCardsi GC14M093170.
HGNCi HGNC:9472. LGMN.
HPAi HPA000799.
HPA001426.
MIMi 602620. gene.
neXtProti NX_Q99538.
PharmGKBi PA30354.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5206.
HOGENOMi HOG000236335.
HOVERGENi HBG031304.
InParanoidi Q99538.
KOi K01369.
OMAi KVMQFQG.
PhylomeDBi Q99538.
TreeFami TF313403.

Enzyme and pathway databases

BRENDAi 3.4.22.34. 2681.
Reactomei REACT_118632. Trafficking and processing of endosomal TLR.
REACT_121399. MHC class II antigen presentation.
REACT_13523. Vitamin D (calciferol) metabolism.
SABIO-RK Q99538.

Miscellaneous databases

ChiTaRSi LGMN. human.
GeneWikii LGMN.
GenomeRNAii 5641.
NextBioi 21918.
PMAP-CutDB Q99538.
PROi Q99538.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q99538.
Bgeei Q99538.
CleanExi HS_LGMN.
Genevestigatori Q99538.

Family and domain databases

InterProi IPR001096. Peptidase_C13.
[Graphical view ]
PANTHERi PTHR12000. PTHR12000. 1 hit.
Pfami PF01650. Peptidase_C13. 1 hit.
[Graphical view ]
PIRSFi PIRSF019663. Legumain. 1 hit.
PRINTSi PR00776. HEMOGLOBNASE.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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, GLYCOSYLATION AT ASN-91; ASN-167; ASN-263 AND ASN-272, SUBUNIT, DOMAIN, MUTAGENESIS OF GLU-190, AUTOCATALYTIC PROCESSING.

Entry informationi

Entry nameiLGMN_HUMAN
AccessioniPrimary (citable) accession number: Q99538
Secondary accession number(s): O00123, Q9BTY1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: September 3, 2014
This is version 134 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

External Data

Dasty 3

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