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NEU1


Official Full Name
neuraminidase 1
Organism
Homo sapiens
Gene ID
4758
Background
The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity. [provided by RefSeq, Jul 2008]
Synonyms
NEU; NANH; SIAL1

Cat.No. Product Name Price
SHH026731 shRNA set against Rat Egfl7(NM_139104.1) Inquiry
SHH283817 shRNA set against Human EGFL7 (NM_201446.2) Inquiry
SHH338655 shRNA set against Rat Matn4 (NM_001106539.1) Inquiry
SHW009688 shRNA set against Danio rerio EGFL7 (NM_001040385) Inquiry
SHW001067 shRNA set against Chicken NEURL (NM_001012910) Inquiry
SHH351500 shRNA set against Rat NEURL (NM_001107605.1) Inquiry
SHH351496 shRNA set against Mouse NEURL (NM_001013414.2) Inquiry
SHH351493 shRNA set against Human NEURL (NM_004210.4) Inquiry
SHH351452 shRNA set against Rat NEU1 (NM_031522.3) Inquiry
SHH351448 shRNA set against Mouse NEU1 (NM_010893.3) Inquiry
SHH351444 shRNA set against Human NEU1 (NM_000434.3) Inquiry
SHH338651 shRNA set against Mouse Matn4 (NM_013592.4) Inquiry
SHH338647 shRNA set against Human Matn4 (NM_003833.3) Inquiry
SHH283825 shRNA set against Rat EGFL7 (NM_139104.1) Inquiry
SHH283821 shRNA set against Mouse EGFL7 (NM_178444.4) Inquiry
SHW009900 shRNA set against Danio rerio NEU1 (NM_001044909) Inquiry
SHW018584 shRNA set against Danio rerio MATN4 (NM_213549) Inquiry
Cat.No. Product Name Price
SKO0029 EGFL7 Validated sgRNA vector Inquiry
CDCR059128 Mouse Egfl7 ORF clone (NM_001164564.1) Inquiry
CDCR381429 Rat Egfl7 ORF Clone(NM_139104.1) Inquiry
CDCS405661 Human NEU1 ORF Clone (BC000722) Inquiry
CDCR274836 Mouse Egfl7 ORF Clone(NM_178444.4) Inquiry
CDFR005705 Rat Matn4 cDNA Clone(NM_001106539.1) Inquiry
MiUTR3H-10101 EGFL7 miRNA 3'UTR clone Inquiry
CDFR012682 Rat Neu1 cDNA Clone(NM_031522.3) Inquiry
CDFR014382 Rat Egfl7 cDNA Clone(NM_139104.1) Inquiry
MiUTR1H-06724 NEU1 miRNA 3'UTR clone Inquiry
MiUTR1R-01666 EGFL7 miRNA 3'UTR clone Inquiry
MiUTR3H-10100 EGFL7 miRNA 3'UTR clone Inquiry
CDFR007290 Rat Neurl cDNA Clone(NM_001107605.1) Inquiry
CDCS415965 Human MATN4 ORF Clone (BC141811) Inquiry
CDCS414213 Human EGFL7 ORF Clone (BC012377) Inquiry
CDCR379715 Rat Neu1 ORF Clone(NM_031522.3) Inquiry
CDCR374340 Rat Neurl ORF Clone(NM_001107605.1) Inquiry
CDCS415966 Human MATN4 ORF Clone (BC131763) Inquiry
CDCR287416 Human NEURL ORF Clone(NM_004210.4) Inquiry
CDCR249795 Mouse Neu1 ORF Clone(NM_010893.3) Inquiry
CDCR059122 Mouse Egfl7 ORF clone (NM_198725.2) Inquiry
CDCL130923 Human MATN4 ORF clone (NM_003833.3) Inquiry
CDCB194184 Rabbit NEURL1 ORF clone (XM_008270468.1) Inquiry
CDCB192401 Rabbit NEU1 ORF clone (XM_002714312.2) Inquiry
CDCB191421 Rabbit CXHXorf58 ORF clone (XM_008272451.1) Inquiry
CDCB186697 Rabbit MATN4 ORF clone (XM_002721209.2) Inquiry
CDCB180059 Danio rerio MATN4 ORF Clone (NM_213549) Inquiry
CDCB171375 Danio rerio NEU1 ORF Clone (NM_001044909) Inquiry
CDCB171163 Danio rerio EGFL7 ORF Clone (NM_001040385) Inquiry
CDCB162542 Chicken NEURL ORF Clone (NM_001012910) Inquiry
CDCB160318 Human EGFL7 ORF clone (NM_016215.3) Inquiry
CDCB160066 Human NEU1 ORF clone (BC000722) Inquiry
CDCB159525 Human MATN4 ORF clone (BC141811) Inquiry
CDCR373323 Rat Matn4 ORF Clone(NM_001106539.1) Inquiry
CDCB157204 Mouse EGFL7 ORF clone (NM_178444.3) Inquiry

Detailed Information

Sialic acid is widely present in living organisms and is often present at the end of the sugar chain of sugar complexes. It is essential for the development of tissues and organs, especially the brain, and is closely related to the occurrence and development of various diseases. When sialic acid is hydrolyzed by sialidase, the conformation of the glycoconjugate can be altered to regulate the biological function of the relevant factor. Sialidase is widely present in living organisms. Four sialidases have been found in mammals. They are named Neu1, Neu2, Neu3 and Neu4 depending on the splicing substrate and the distribution within the cell. Among them, the study of Neu1 is more in-depth.

The Biological Function of NEU1

Neu1 is expressed in lysosomes, and it needs to form a complex with protective protein/cathepsin A (PPCA) and β-gal (β-galactosidase) to exert its function. The activity of PPCA is not necessary for the activity of Neu1 and β-gal enzymes. It acts as a molecular chaperone to help Neu1 fold, stabilize, oligomerize and activate. When PPCA depolymerizes with Neu1, it can cause compound dissociation and Neu1 inactivation.

Elastin-binding protein (EBP) is a β-gal cleavage mutant that forms a complex with Neu1 and PPCA on the cell surface. Cell surface Neu1 activity is a prerequisite for the release of elastin. Sialidase inhibitors inhibit the assembly of elastin fibers in human dermal fibroblasts, aortic smooth muscle cells, and the formation of elastic fibers, which can be successfully reversed when exogenously overexpressing Neu1.

Neu1-mediated Cellular Receptor Signaling

EGFR is a cell surface receptor glycoprotein belonging to the epidermal growth factor family and has receptor tyrosine kinases activity that can be recognized by a variety of ligands. On the cell surface, MUC1 regulates the EGFR signaling pathway by interacting with EGFR. Using immunohistochemistry, it was found that in triple-negative breast cancer, the expression of EGFR was significantly increased compared with the normal group, and the expression of Neu1 was down-regulated, and the degree of autophagy in cancer tissues was significantly lower than that in normal tissues. By analyzing their correlation, it was found that EGFR-MUC1-Neu1 complex abnormality caused by decreased autophagy in triple-negative breast cancer, leading to changes in its related signaling pathway, indicating that Neu1 is involved in lysosomal pathway-mediated autophagy and endocytosis.

Neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP9) cross-talk in alliance with G proteincoupled receptor(s) (GPCR) regulates receptor tyrosine kinases (RTKs). Figure 1. Neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP9) cross-talk in alliance with G proteincoupled receptor(s) (GPCR) regulates receptor tyrosine kinases (RTKs). (Haxho, F., et al. 2015)

NEU1 and Tumor

The change in the expression level of Neu1 is also related to the degree of deterioration of various tumors. Neu1 can inhibit the extracellular secretion of lysosome by shearing the sialic acid modification of LAMP1. As the extracellular secretion of lysosomes in tumor cells is aggravated, the secretion of hydrolases and exosomes increases, which promotes the invasion of the matrix and the spread of invasive signals and the clearance of chemotherapy drugs. In the mouse model of Arf knockout (Arf -/-), it was found that low expression of Neu1 (Neu1+/-) facilitates the formation of invasive pleomorphic sarcoma, promotes epithelial and mesenchymal cell marker molecules, and increases the expression of the extracellular secreted factors LAMP1 and Myosin-11. These characteristics are similar to those of human metastatic pleomorphic sarcoma, suggesting that lysosomal regulatory pathways are critical for tumor development and drug resistance. Thus, it has been proposed to inhibit tumor invasion and drug resistance by inhibiting the extracellular secretion of lysosomes.

Overexpression of Neu1 in malignant melanoma cells B16-BL6, cells showed inhibition of lung metastasis and tumor formation, cell growth retardation, and increased sensitivity to apoptosis. When the colon cancer cell line HT29 overexpressing Neu1 was injected into the spleen of mice, its ability to metastasize to the liver was significantly lower than that of the control group, and it was found that Neu1 can cause its phosphorylation down-regulation by hydrolyzing sialic acid on Integrin β4, which in turn inhibits FAK (focal adhesion kinase) activity and ERK1/2 (extracellular signal-regulated kinase 1/2) signaling pathway.

References:

  1. Haxho, F. , Neufeld, R. J. , & Szewczuk, M. R. . (2015). Neuraminidase-1: a novel therapeutic target in multistage tumorigenesis. Oncotarget, 7(26).
  2. D'Azzo, A., Machado, E., & Annunziata, I. (2015). Pathogenesis, emerging therapeutic targets and treatment in sialidosis. Expert Opinion on Orphan Drugs, 3(5), 491.
  3. Kwak, J. E. , Son, M. Y. , Son, Y. S. , Son, M. J. , & Cho, Y. S. . (2015). Biochemical and molecular characterization of novel mutations in glb1 and neu1 in patient cells with lysosomal storage disorders. Biochemical and Biophysical Research Communications, 457(4), 554-560.
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