Q99538 (LGMN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Legumain
EC=3.4.22.34

Alternative name(s):
Asparaginyl endopeptidase
Protease, cysteine 1

Gene names

Name:	LGMN
Synonyms:	PRSC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	433 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system.
Catalytic activity	Hydrolysis of proteins and small molecule substrates at -Asn-|-Xaa- bonds.
Subcellular location	Lysosome By similarity.
Tissue specificity	Ubiquitous. Particularly abundant in kidney, heart and placenta.
Post-translational modification	Glycosylated.
Sequence similarities	Belongs to the peptidase C13 family.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Thiol protease
PTM	Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antigen 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 multicellular organism growth Inferred from electronic annotation. Source: Compara 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 response to acid Inferred from electronic annotation. Source: Compara vitamin D metabolic process Traceable author statement. Source: Reactome
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara late endosome Inferred from electronic annotation. Source: Compara lysosomal lumen Traceable author statement. Source: Reactome
Molecular_function	cysteine-type endopeptidase activity Inferred from sequence or structural similarity Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Ref.4
	Chain	18 – 323	306	Legumain		PRO_0000026502
	Propeptide	324 – 433	110			PRO_0000026503
Sites
	Active site	148	1	Potential
	Active site	189	1	Potential
	Site	323 – 324	2	Cleavage; by autolysis
Amino acid modifications
	Glycosylation	91	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	167	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	263	1	N-linked (GlcNAc...) Potential
	Glycosylation	272	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	18	1	V → I. Ref.3 Corresponds to variant rs2236264 [ dbSNP | Ensembl ].		VAR_024588
Experimental info
	Mutagenesis	323	1	N → D, Q or S: Loss of autoactivation.
	Sequence conflict	31	1	V → A in BAA09530. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q99538 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 081AD2D0D584E72A	FASTA	433	49,411
	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

References

	« Hide 'large scale' referencesShow '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.
[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, MASS SPECTROMETRY. 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].
+	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.
IPI	IPI00293303.
RefSeq	NP_001008530.1. NM_001008530.2. NP_005597.3. NM_005606.6.
UniGene	Hs.741226.
3D structure databases
ProteinModelPortal	Q99538.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99538. 4 interactions.
STRING	9606.ENSP00000334052.
Protein family/group databases
MEROPS	C13.004.
PTM databases
PhosphoSite	Q99538.
Polymorphism databases
DMDM	2842759.
Proteomic databases
PaxDb	Q99538.
PRIDE	Q99538.
Protocols and materials databases
DNASU	5641.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334869; ENSP00000334052; ENSG00000100600. ENST00000393218; ENSP00000376911; ENSG00000100600.
GeneID	5641.
KEGG	hsa:5641.
UCSC	uc001yav.3. human.
Organism-specific databases
CTD	5641.
GeneCards	GC14M093170.
HGNC	HGNC:9472. LGMN.
HPA	HPA001426.
MIM	602620. gene.
neXtProt	NX_Q99538.
PharmGKB	PA30354.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5206.
HOGENOM	HOG000236335.
HOVERGEN	HBG031304.
InParanoid	Q99538.
KO	K01369.
OMA	FPNDDLH.
PhylomeDB	Q99538.
Enzyme and pathway databases
BRENDA	3.4.22.34. 2681.
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones. REACT_6900. Immune System.
SABIO-RK	Q99538.
Gene expression databases
ArrayExpress	Q99538.
Bgee	Q99538.
CleanEx	HS_LGMN.
Genevestigator	Q99538.
GermOnline	ENSG00000100600. Homo sapiens.
Family and domain databases
InterPro	IPR001096. Peptidase_C13. [Graphical view]
PANTHER	PTHR12000. PTHR12000. 1 hit.
Pfam	PF01650. Peptidase_C13. 1 hit. [Graphical view]
PIRSF	PIRSF019663. Legumain. 1 hit.
PRINTS	PR00776. HEMOGLOBNASE.
ProtoNet	Search...
Other
BindingDB	Q99538.
ChEMBL	CHEMBL4244.
ChiTaRS	LGMN. human.
GenomeRNAi	5641.
NextBio	21918.
PMAP-CutDB	Q99538.
SOURCE	Search...

Entry information

Entry name

LGMN_HUMAN

Accession

Primary (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 3, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.