Lgmn legumain [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Lgmnprovided by MGI
Official Full Name: legumainprovided by MGI
Primary source: MGI:MGI:1330838
See related: Ensembl:ENSMUSG00000021190 AllianceGenome:MGI:1330838
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: AEP; Prsc1
Summary: This gene encodes a member of the cysteine peptidase family C13 that plays an important role in the endosome/lysosomal degradation system. The encoded inactive preproprotein undergoes autocatalytic removal of the C-terminal inhibitory propeptide to generate the active endopeptidase that cleaves protein substrates on the C-terminal side of asparagine residues. Mice lacking the encoded protein exhibit defects in the lysosomal processing of proteins resulting in their accumulation in the lysosomes, and develop symptoms resembling hemophagocytic lymphohistiocytosis. [provided by RefSeq, Aug 2016]
Expression: Broad expression in kidney adult (RPKM 276.6), placenta adult (RPKM 128.8) and 20 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 E; 12 51.45 cM

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (102360341..102405987, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (102394082..102439728, complement)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Legumain-deficient macrophages regulate inflammation and lipid metabolism in adipose tissues to protect against diet-induced obesity.
Title: Legumain-deficient macrophages regulate inflammation and lipid metabolism in adipose tissues to protect against diet-induced obesity.
CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6.
Title: CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6.
Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.
Title: Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.
Asparagine endopeptidase protects podocytes in adriamycin-induced nephropathy by regulating actin dynamics through cleaving transgelin.
Title: Asparagine endopeptidase protects podocytes in adriamycin-induced nephropathy by regulating actin dynamics through cleaving transgelin.
Legumain Is an Endogenous Modulator of Integrin alphavbeta3 Triggering Vascular Degeneration, Dissection, and Rupture.
Title: Legumain Is an Endogenous Modulator of Integrin αvβ3 Triggering Vascular Degeneration, Dissection, and Rupture.
Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice.
Title: Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice.
Legumain Knockout Protects Against Abeta1-42-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP.
Title: Legumain Knockout Protects Against Aβ(1-42)-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP.
ADAM10 and ADAM17 are degraded by lysosomal pathway via asparagine endopeptidase.
Title: ADAM10 and ADAM17 are degraded by lysosomal pathway via asparagine endopeptidase.
Lgmn was upregulated in lung tissues of PAH mice subjected to hypoxia(HySu) plus SU5416. Deletion of Lgmn systemically inhibits the development of PAH by diminishing ECM protein accumulation in PAs from HySu-treated mice.The synthetic specific Lgmn inhibitor RR-11a protects against PAH. Lgmn promotes ECM protein deposition in PAs involved in activating TGF-beta1.
Title: Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-β1 Signaling.
Study shows that BDNF-mediated Akt directly phosphorylates AEP on T322 and blocks AEP activation, sequestering it in lysosomes. Viral delivery of unphosphorylated T322A mutant into brain of young alpha-SNCA mice accelerates alpha-syn N103 cleavage in alpha-SNCA-Tg mice. Data support the hypothesis that a decrease in BDNF/TrkB signaling in neurodegenerative diseases abolishes p-AEP T322, resulting in AEP upregulation an...
Title: BDNF inhibits neurodegenerative disease-associated asparaginyl endopeptidase activity via phosphorylation by AKT.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Gene trapped (1)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

LGMN-1 (e-PCR)
- UniSTS:511834

AU022324 (e-PCR)
- UniSTS:208854

AI746452 (e-PCR)
- UniSTS:160246

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables endopeptidase activator activity	IEA Inferred from Electronic Annotation more info
enables endopeptidase activator activity	ISO Inferred from Sequence Orthology more info
enables peptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables peptidase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in activation of cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II	ISO Inferred from Sequence Orthology more info
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II	ISS Inferred from Sequence or Structural Similarity more info
involved_in associative learning	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to amyloid-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amyloid-beta	ISO Inferred from Sequence Orthology more info
involved_in cellular response to calcium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to calcium ion	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hepatocyte growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hepatocyte growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in dendritic spine organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in memory	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of ERBB signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of endothelial cell chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of long-term synaptic potentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of monocyte chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of monocyte chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in protein maturation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis involved in protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis involved in protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in renal system process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to acidic pH	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to acidic pH	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to acidic pH	ISO Inferred from Sequence Orthology more info
involved_in self proteolysis	IEA Inferred from Electronic Annotation more info
involved_in self proteolysis	ISO Inferred from Sequence Orthology more info
involved_in vacuolar protein processing	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in apical part of cell	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular region	ISO Inferred from Sequence Orthology more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in lysosomal lumen	ISO Inferred from Sequence Orthology more info
is_active_in lysosomal lumen	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: legumain

Names: asparaginyl endopeptidase; preprolegumain; protease, cysteine, 1

NP_001365804.1

EC 3.4.22.34

NP_035305.1

EC 3.4.22.34

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001378875.1 → NP_001365804.1 legumain preproprotein

Status: REVIEWED

Source sequence(s)

AC122302

UniProtKB/Swiss-Prot

O89017

UniProtKB/TrEMBL

A2RTI3

Related

ENSMUSP00000105647.2, ENSMUST00000110020.8

Conserved Domains (2) summary

pfam01650
Location:31 → 287

Peptidase_C13; Peptidase C13 family

cd21115
Location:311 → 431

legumain_C; C-terminal prodomain of legumain
NM_011175.4 → NP_035305.1 legumain preproprotein

See identical proteins and their annotated locations for NP_035305.1

Status: REVIEWED

Source sequence(s)

AC122302

Consensus CDS

CCDS26119.1

UniProtKB/Swiss-Prot

O89017

UniProtKB/TrEMBL

A2RTI3

Related

ENSMUSP00000021607.9, ENSMUST00000021607.9

Conserved Domains (2) summary

pfam01650
Location:31 → 287

Peptidase_C13; Peptidase C13 family

cd21115
Location:311 → 431

legumain_C; C-terminal prodomain of legumain