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Tchem
NEU3
Sialidase-3
Protein Summary
Description
Plays a role in modulating the ganglioside content of the lipid bilayer at the level of membrane-bound sialyl glycoconjugates. This gene product belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipids. It is localized in the plasma membrane, and its activity is specific for gangliosides. It may play a role in modulating the ganglioside content of the lipid bilayer. [provided by RefSeq, Jul 2008]
These are targets about which virtually nothing is known. They do not have known drug or small molecule activities - AND - satisfy two or more of the following criteria:
GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.
Results are shown as five categories: (▲▲) significantly up-regulated,
(▲) non-significantly up-regulated, (▼) non-significantly down-regulated,
(▼▼) significantly down-regulated, and not (-) found.
For selected nodes the values are shown on the right hand side.
The median is flagged in a different colour for nodes with multiple
expression values.
Reactome is a manually curated, peer reviewed knowledgebase of human biological pathways and processes, available online as an open access resource that can be freely used and distributed by all members of the biological research community. This view of the Reactome database displays the pathways functionally interacting with NEU3.
Overrepresented Terms from Abstracts 100 terms from up to 100 abstracts, scaled based on the degree of overrepresentation (Fisher's Exact Test p-Value).
Kirolos et al., Journal of leukocyte biology, 2022-12
Abstract: (show)
Some extracellular glycoconjugates have sialic acid as the terminal sugar, and sialidases are enzymes that remove this sugar. Mammals have 4 sialidases and can be elevated in inflammation and fibrosis. In this report, we show that incubation of human neutrophils with the extracellular human sialidase NEU3, but not NEU1, NEU2 or NEU4, induces human male and female neutrophils to change from a round to a more amoeboid morphology, causes the primed human neutrophil markers CD11b, CD18, and CD66a to localize to the cell cortex, and decreases the localization of the unprimed human neutrophil markers CD43 and CD62-L at the cell cortex. NEU3, but not the other 3 sialidases, also causes human male and female neutrophils to increase their F-actin content. Human neutrophils treated with NEU3 show a decrease in cortical levels of Sambucus nigra lectin staining and an increase in cortical levels of peanut agglutinin staining, indicating a NEU3-induced desialylation. The inhibition of NEU3 by the NEU3 inhibitor 2-acetylpyridine attenuated the NEU3 effect on neutrophil morphology, indicating that the effect of NEU3 is dependent on its enzymatic activity. Together, these results indicate that NEU3 can prime human male and female neutrophils, and that NEU3 is a potential regulator of inflammation.
Taeko Miyagi, Koji Yamamoto, Glycoconjugate journal, 2022-10
Abstract: (show)
Sialidases (EC 3.2.1.18, also called neuraminidases) catalyze the removal of α-glycosidically linked sialic acid residues from glycoproteins and glycolipids; this is the initial step in the degradation of these glycoconjugates. Sialidases of mammalian origin have been implicated in not only lysosomal catabolism but also the modulation of functional molecules involved in many biological processes. To date, four types of mammalian sialidases have been cloned and designated as Neu1, Neu2, Neu3 and Neu4. These sialidases differ in their subcellular localization and enzymatic properties, as well as their chromosomal localization, and they are expressed in a tissue-specific manner. Among the sialidases, the plasma membrane-associated sialidase Neu3 appears to play particular roles in controlling transmembrane signaling through the modulation of gangliosides, and its aberrant expression is closely related to various pathogeneses, including that of cancer. Interestingly, the human orthologue NEU3 acts in two ways, catalytic hydrolysis of gangliosides and protein interactions with other signaling molecules. Aberrant NEU3 expression can induce various pathological conditions. This review briefly summarizes recent studies, focusing on the involvement of NEU3 in various pathological phenomena.
Bovio et al., International journal of molecular sciences, 2020-11-20
Abstract: (show)
The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors' activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway. In order to better understand the EGFR-NEU3 interplay and the mechanisms of pharmacological resistance, we investigated the role of NEU3 deregulation in cetuximab-treated CRC cell lines transiently transfected with NEU3 using Western blot analysis. Our results indicate that NEU3 overexpression can enhance EGFR activation only if EGFR is overexpressed, indicating the existence of a threshold for NEU3-mediated EGFR activation. This enhancement mainly leads to the constitutive activation of the MAP kinase pathway. Consequently, we suggest that the evaluation of NEU3 expression cannot entirely substitute the evaluation of EGFR because EGFR-negative cases cannot be stimulated by NEU3. Furthermore, NEU3-mediated hyperactivation of EGFR is counterbalanced by the administration of cetuximab, hypothesizing that a combined treatment of NEU3- and EGFR-targeted therapies may represent a valid option for CRC patients, which must be investigated in the future.
Ghiroldi et al., The Biochemical journal, 2020-09-18
Abstract: (show)
Cardiac fibrosis is a key physiological response to cardiac tissue injury to protect the heart from wall rupture. However, its progression increases heart stiffness, eventually causing a decrease in heart contractility. Unfortunately, to date, no efficient antifibrotic therapies are available to the clinic. This is primarily due to the complexity of the process, which involves several cell types and signaling pathways. For instance, the transforming growth factor beta (TGF-β) signaling pathway has been recognized to be vital for myofibroblasts activation and fibrosis progression. In this context, complex sphingolipids, such as ganglioside GM3, have been shown to be directly involved in TGF-β receptor 1 (TGF-R1) activation. In this work, we report that an induced up-regulation of sialidase Neu3, a glycohydrolytic enzyme involved in ganglioside cell homeostasis, can significantly reduce cardiac fibrosis in primary cultures of human cardiac fibroblasts by inhibiting the TGF-β signaling pathway, ultimately decreasing collagen I deposition. These results support the notion that modulating ganglioside GM3 cell content could represent a novel therapeutic approach for cardiac fibrosis, warranting for further investigations.
Pulmonary fibrosis is a chronic and generally fatal disorder characterized by progressive formation of scar-like tissue in the lungs. Sialic acids are often found as the terminal sugar on extracellular glycoconjugates such as protein glycosylations. Sialidases, also known as neuraminidases, desialylate glycoconjugates. Serum amyloid P (SAP), a pentameric serum glycoprotein that has two sialic acids on each polypeptide, inhibits the differentiation of monocytes into fibrocytes and promotes human PBMCs to accumulate high extracellular levels of IL-10. When SAP is desialylated with sialidase, the effects of SAP on fibrocyte differentiation and IL-10 accumulation are strongly inhibited. Intriguingly, in patients with pulmonary fibrosis, there are increased levels of sialidase activity in the bronchoalveolar lavage fluid, increased levels of sialidases in the lungs, and decreased levels of SAP in the sera. To elucidate the role of SAP desialylation in idiopathic pulmonary fibrosis (IPF) pathogenesis, we purified SAP from the serum of IPF patients and healthy controls and measured the extent of sialylation and bioactivity of the purified SAP. We find that some IPF patients have abnormally high levels of the sialidase NEU3 in their sera and that the SAP in the sera of IPF patients has an abnormally high extent of desialylation and an abnormally low ability to inhibit fibrocyte differentiation and induce extracellular IL-10 accumulation by PBMC. These results suggest that SAP desialylation may play a role in IPF pathogenesis and that inhibiting NEU3 could be a potential therapeutic target for IPF.
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Description of the protein which includes the UniProt Function and the NCBI Gene Summary.
Uniprot linked accession values, symbols or commonly used abbreviations associated with this particular target.
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Group 10 secretory phospholipase A2
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Function terms describe molecular activities performed by gene products. Terms may be broad, such as "catalytic activity" or narrow, such as "adenylate cyclase activity".
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This component shows publications, as determined by manual curation and entity matching to text in the title or abstract. Displayed data is from NCBI. Additional references based on entity matching to the abstracts and full text (when available) from JensenLab is available in the download. Click the "?" for more details.
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The KEGG Pathways a target has in common with the main target for this Details Page
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There are several new features in Pharos version 3.18, including updated data for Publications and Expression, and added features for displaying data from the Pharos community.