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    Lgmn legumain [ Mus musculus (house mouse) ]

    Gene ID: 19141, updated on 13-Jul-2021

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    ADAM10 and ADAM17 are degraded by lysosomal pathway via asparagine endopeptidase.

    ADAM10 and ADAM17 are degraded by lysosomal pathway via asparagine endopeptidase.
    Zhang X, Tang L, Zhang Z.

    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.

    Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-β1 Signaling.
    Bai P, Lyu L, Yu T, Zuo C, Fu J, He Y, Wan Q, Wan N, Jia D, Lyu A.

    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...

    BDNF inhibits neurodegenerative disease-associated asparaginyl endopeptidase activity via phosphorylation by AKT.
    Wang ZH, Wu W, Kang SS, Liu X, Wu Z, Peng J, Yu SP, Manfredsson FP, Sandoval IM, Liu X, Wang JZ, Ye K., Free PMC Article

    AEP mediates tau-splicing imbalance in tauopathies via cleaving SRPK2.

    Delta-secretase (AEP) mediates tau-splicing imbalance and accelerates cognitive decline in tauopathies.
    Wang ZH, Liu P, Liu X, Yu SP, Wang JZ, Ye K., Free PMC Article

    Asparagine endopeptidase knockout (AEP KO) displayed lower anxiety-like behavior and more advanced exploratory behavior, reduced depressive-like behaviors, and elevated spatial learning and memory ability. Enhanced synaptic plasticity as well as the increased expressions of SYP and PSD-95 proteins in hippocampus were shown in AEP KO mice. BDNF protein was reduced and NF-kappaB p65 protein was increased in their hippoca...

    Deletion of asparagine endopeptidase reduces anxiety- and depressive-like behaviors and improves abilities of spatial cognition in mice.
    Gao J, Li K, Du L, Yin H, Tan X, Yang Z.

    findings thus support that AEP-mediated cleavage of alpha-Syn at N103 is required for the association and activation of MAO-B, mediating Parkinson's disease pathogenesis.

    α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease.
    Kang SS, Ahn EH, Zhang Z, Liu X, Manfredsson FP, Sandoval IM, Dhakal S, Iuvone PM, Cao X, Ye K., Free PMC Article

    Legumain regulates oxLDL-induced macrophage apoptosis by enhancing the autophagy pathway.

    Legumain suppresses OxLDL-induced macrophage apoptosis through enhancement of the autophagy pathway.
    Sun W, Lin Y, Chen L, Ma R, Cao J, Yao J, Chen K, Wan J.

    Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

    Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.
    Jafari A, Qanie D, Andersen TL, Zhang Y, Chen L, Postert B, Parsons S, Ditzel N, Khosla S, Johansen HT, Kjærsgaard-Andersen P, Delaisse JM, Abdallah BM, Hesselson D, Solberg R, Kassem M., Free PMC Article

    This study showed that legumain may serve as a biomarker of disease, and that the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer.

    Legumain is activated in macrophages during pancreatitis.
    Edgington-Mitchell LE, Wartmann T, Fleming AK, Gocheva V, van der Linden WA, Withana NP, Verdoes M, Aurelio L, Edgington-Mitchell D, Lieu T, Parker BS, Graham B, Reinheckel T, Furness JB, Joyce JA, Storz P, Halangk W, Bogyo M, Bunnett NW., Free PMC Article

    AEP acts as a delta-secretase, cleaving APP at N373 and N585 residues, selectively influencing the amyloidogenic fragmentation of APP. AEP contributes to the age-dependent pathogenic mechanisms in Alzheimer disease.

    Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease.
    Zhang Z, Song M, Liu X, Su Kang S, Duong DM, Seyfried NT, Cao X, Cheng L, Sun YE, Ping Yu S, Jia J, Levey AI, Ye K., Free PMC Article

    results suggest that legumain expression and activation and cleavage of annexin A2 are regulated by DJ-1 through p53

    Expression and protease activity of mouse legumain are regulated by the oncogene/transcription co-activator, DJ-1 through p53 and cleavage of annexin A2 is increased in DJ-1-knockout cells.
    Yamane T, Yamamoto Y, Nakano Y, Nakagaki T, Ohkubo I, Ariga H.

    AEP acts as a crucial mediator of tau-related clinical and neuropathological changes.

    Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease.
    Zhang Z, Song M, Liu X, Kang SS, Kwon IS, Duong DM, Seyfried NT, Hu WT, Liu Z, Wang JZ, Cheng L, Sun YE, Yu SP, Levey AI, Ye K., Free PMC Article

    TDP-43 is cleaved by AEP in brain.

    Asparaginyl endopeptidase cleaves TDP-43 in brain.
    Herskowitz JH, Gozal YM, Duong DM, Dammer EB, Gearing M, Ye K, Lah JJ, Peng J, Levey AI, Seyfried NT., Free PMC Article

    TLR7 requires a proteolytic cleavage by AEP to generate a C-terminal fragment competent for signaling.

    Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
    Maschalidi S, Hässler S, Blanc F, Sepulveda FE, Tohme M, Chignard M, van Endert P, Si-Tahar M, Descamps D, Manoury B., Free PMC Article

    We identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum toxin substrate 2 (RAC2), among others, in an invasive pre-B-cell line that produced leukemia in NOD-SCID mice

    RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia.
    Holland M, Castro FV, Alexander S, Smith D, Liu J, Walker M, Bitton D, Mulryan K, Ashton G, Blaylock M, Bagley S, Connolly Y, Bridgeman J, Miller C, Krishnan S, Dempsey C, Masurekar A, Stern P, Whetton A, Saha V.

    AEP is required for normal protein catabolism by PTCs, and its loss induces proliferative and other abnormalities in the murine kidney, at least in part through defective regulation of the EGF receptor

    Asparagine endopeptidase is required for normal kidney physiology and homeostasis.
    Miller G, Matthews SP, Reinheckel T, Fleming S, Watts C.

    Immunohistochemical analyses revealed the expression of legumain in Iba1(+) microglial cells and glial fibrillary acidic protein-positive astrocytes of the peri-infarct area in mice after transient occlusion of the middle cerebral artery.

    The asparaginyl endopeptidase legumain after experimental stroke.
    Ishizaki T, Erickson A, Kuric E, Shamloo M, Hara-Nishimura I, Inácio AR, Wieloch T, Ruscher K., Free PMC Article

    mutant mice lacking AEP develop fever, cytopenia, hepatosplenomegaly, and hemophagocytosis, extramedullary hematopoiesis in the spleen and abnormally enlarged histiocytes with ingested red blood cells in bone marrow.

    Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome.
    Chan CB, Abe M, Hashimoto N, Hao C, Williams IR, Liu X, Nakao S, Yamamoto A, Zheng C, Henter JI, Meeths M, Nordenskjold M, Li SY, Hara-Nishimura I, Asano M, Ye K., Free PMC Article

    AEP has a pivotal role in the endosomal/lysosomal degradation system

    Biosynthetic processing of cathepsins and lysosomal degradation are abolished in asparaginyl endopeptidase-deficient mice.
    Shirahama-Noda K, Yamamoto A, Sugihara K, Hashimoto N, Asano M, Nishimura M, Hara-Nishimura I.

    Legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells.

    Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells.
    Morita Y, Araki H, Sugimoto T, Takeuchi K, Yamane T, Maeda T, Yamamoto Y, Nishi K, Asano M, Shirahama-Noda K, Nishimura M, Uzu T, Hara-Nishimura I, Koya D, Kashiwagi A, Ohkubo I.

    Lysosomal asparaginyl endopeptidase (AEP) is essential for processing of cathepsin L but not for class II major histocompatibility complex (MHC)-restricted antigen presentation.

    Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice.
    Maehr R, Hang HC, Mintern JD, Kim YM, Cuvillier A, Nishimura M, Yamada K, Shirahama-Noda K, Hara-Nishimura I, Ploegh HL.

    unrestricted legumain activity is involved in disturbed epidermal cornification in cystatin M/E deficient mice.

    Evidence that unrestricted legumain activity is involved in disturbed epidermal cornification in cystatin M/E deficient mice.
    Zeeuwen PL, van Vlijmen-Willems IM, Olthuis D, Johansen HT, Hitomi K, Hara-Nishimura I, Powers JC, James KE, op den Camp HJ, Lemmens R, Schalkwijk J.

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