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Tbio Sialidase-1

Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.

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]

 Comments

Property Summary

NCBI Gene PubMed Count 69
PubMed Score 112.45
PubTator Score 5959.55

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count Z-score Confidence
Rheumatoid Arthritis 1170 0.0 2.0
Type 1 diabetes mellitus 104 0.0 2.0
Vitiligo 71 0.0 2.0
Disease Target Count
Glycoproteinosis 13
Sialidosis type 1 1
Disease Target Count
Sialidosis 1

Expression

  Differential Expression (6)

Disease log2 FC p
Multiple myeloma 1.147 1.4e-03
glioblastoma 1.300 9.5e-03
medulloblastoma, large-cell -1.100 2.8e-04
intraductal papillary-mucinous neoplasm ... -1.100 6.6e-03
ulcerative colitis -1.600 2.2e-05
ovarian cancer 1.400 1.1e-04

Synonym

Accession Q99519
Symbols NEU
NANH
SIAL1

Gene

NEU1

PANTHER Protein Class (1)

  Ortholog (1)

Species Source Disease
Macaque OMA Inparanoid

 UniProt Keyword (18)

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 GO Function (4)

 GO Component (9)

 GO Process (3)

 Compartment GO Term (45)

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 OMIM Phenotype (2)

 MGI Phenotype (16)

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 HCA RNA Cell Line (56)

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 CSPA Cell Line (3)

Pathway (18)

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Protein-protein Interaction (3)

CTSA   GM2A   SLC17A5  

Gene RIF (43)

PMID Text
26768362 Our study shows that the 340-cavity is not an occasional or atypical domain in NA subtypes, and it has potential to function as a new hotspot for influenza drug binding.
26463994 NEU1 siRNA can effectively inhibit proliferation, apoptosis, and invasion of human ovarian cancer cells by targeting lysosome and oxidative phosphorylation signaling, which can serve as a new target ovarian cancer treatment
26455375 How the point mutations of the neuraminidase sequences affected the susceptibility of H9N2 virus to oseltamivir is still to be determined and deserve further investigations
26185093 Neu1 desialylation is a mechanism of Fc-independent platelet clearance in immune thrombocytopenia.
26086247 Basal Neu-1 catalytic activity is strongly increased in aged cells.
25963144 Flagellin drives NEU1 to desialylate MUC1, thereby increasing its adhesiveness for Pseudomonas aeruginosa and its shedding
25925251 Muc1 clearly plays a significant role in enhancing the hypoxia-inducible transcription factors protective pathway during ischemic insult and recovery in kidney epithelia
25600812 This study analyzed patient cells with GM1 gangliosidosis and sialidosis. A novel mutation p.R347Q is identified in NEU1 gene.
25566667 The lymphocyte levels of NEU1 and ST6GAL1 mRNA expression are significantly increased in erythremia.
24808020 Sialidosis should be suspected and the NEU1 gene analyzed in patients with isolated action myoclonus presenting in adulthood in the absence of other typical clinical and laboratory findings.
24583283 Insulin-induced phosphorylation of the insulin receptor is dependent on Neu1 sialidase activity.
24550400 catalytically active NEU1 inhibits in vitro angiogenesis through desialylation of its substrate, CD31
23391804 Three novel mutations in the NEU1 gene in two Indian patients of sialidosis, one with the type I form and the other with the infantile type II form are reported here.
23291686 NEU1 gene missense mutation was found in a patient diagnosed with type I sialoidosis.
22989879 Data indicate that sialidases Neu1 and Neu3 are present on sperm, and their activity is required for capacitation and zona pellucida binding.
22903576 Weak anchorage of NEU1 and NEU3 to the plasma membrane and their loss during erythrocyte life could be a tool to preserve the cellular sialic acid content to avoid early aging of erythrocyte and processes of cell aggregation in the capillaries.
22403397 Data show that NEU1 was immunolocalized to both the plasma membrane and the perinuclear region, and NEU3 was detected both in the cytosol and nucleus.
22247545 human airway epithelia express catalytically active NEU1 sialidase that regulates EGFR- and MUC1-dependent signaling and bacterial adhesion.
21928149 Neuraminidase 1 as a modulator of cell receptors. (Review)
21873432 a novel Neu1 and MMP9 cross-talk in alliance with TLR4 on the cell surface that is essential for ligand activation of TLRs and subsequent cellular signaling.
21551251 colocalized with CD18 in PMNs; could be a physiologic source of the enzymatic activity that removes sialyl residues on beta2 integrin and ICAM-1, resulting in their enhanced interaction
21103358 Data show that Neu-1 siRNA blocks the process of GM(3)/LacCer conversion.
19851445 Observational study of gene-disease association. (HuGE Navigator)
19686243 occurrence of Neu3 in the inner membrane and Neu1 in the outer membrane of the nuclear envelope
19666471 Results describe the hydrodynamic properties of PPCA, NEU1, and a complex of the two proteins and identified multiple binding sites on both proteins.
19568825 The genetic characterization of the two patients showed one known [c. 679G > A (p.G227R)] NEU1 missense mutation (detected in P2), and the new c.807 + 1G > A splicing defect
19473359 findings show homozygous mutations of NEU1 544A-->G (Ser182Gly substitution) play a major role of the genotype and phenotype of Sialidosis type 1
19460752 Knockdown of sialidase 1 (lysosomal sialidase; NEU1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells
19151752 results suggest that NEU1 is important in regulation of integrin beta4-mediated signaling, leading to suppression of metastasis
18772331 Neuraminidase caused the desialylation of both PDGF and IGF-1 receptors and diminished the intracellular signals induced by the mitogenic ligands PDGF-BB and IGF-2.
18651674 related to malignancy and may be potential targets for cancer diagnosis and therapy
18606142 NEU1 is a negative regulator of lysosomal exocytosis.
17562335 Female cervical mucus contains an endogenous menstrual cycle-related sialidase that could be involved in modifying the rheologic properties of mucus to favor sperm progression at fertilization.
17480010 Observational study of gene-disease association. (HuGE Navigator)
17028199 Activation of lymphocytes resulted in a ninefold increase in Neu1-specific activity after growth of cells in culture for 5 days.Cell surface Neu1 was found tightly associated with a subunit of protective protein/cathepsin A (PPCA).
16835219 upregulation of the Neu1 expression is important for the primary function of macrophages and there is a link between Neu1 and the cellular immune response
16538002 effects of GLB1, PPCA and NEU1 gene mutations on elastogenesis in skin fibroblasts
16314420 Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface to facilitate elastic fiber assembly
15885103 Data show that the differentiation of monocytes into macrophages is associated with regulation of the expression of at least three distinct cellular sialidases, Neu1, 3, and 4, with specific up-regulation of the enzyme activity of only Neu1.
14695530 type II sialidosis associated mutations in NEU1 affect lysosomal sialidase activity.
14517945 Summary of NEU1 mutations found in sialidosis patients.
12487819 Removal of sialic acids from HIV-1 gp120 with neuraminidase (NA) enhances mannose-binding lectin (MBL) binding
8892864 Removal of sialic acids from HIV-1 gp120 with neuraminidase (NA) enhances mannose-binding lectin (MBL) binding

AA Sequence 

MTGERPSTALPDRRWGPRILGFWGGCRVWVFAAIFLLLSLAASWSKAENDFGLVQPLVTMEQLLWVSGRQ      1 - 70
IGSVDTFRIPLITATPRGTLLAFAEARKMSSSDEGAKFIALRRSMDQGSTWSPTAFIVNDGDVPDGLNLG     71 - 140
AVVSDVETGVVFLFYSLCAHKAGCQVASTMLVWSKDDGVSWSTPRNLSLDIGTEVFAPGPGSGIQKQREP    141 - 210
RKGRLIVCGHGTLERDGVFCLLSDDHGASWRYGSGVSGIPYGQPKQENDFNPDECQPYELPDGSVVINAR    211 - 280
NQNNYHCHCRIVLRSYDACDTLRPRDVTFDPELVDPVVAAGAVVTSSGIVFFSNPAHPEFRVNLTLRWSF    281 - 350
SNGTSWRKETVQLWPGPSGYSSLATLEGSMDGEEQAPQLYVLYEKGRNHYTESISVAKISVYGTL         351 - 415
//

Text Mined References (71)

PMID Year Title
26768362 2016 The 340-cavity in neuraminidase provides new opportunities for influenza drug development: A molecular dynamics simulation study.
26463994 2016 Effects of sialidase NEU1 siRNA on proliferation, apoptosis, and invasion in human ovarian cancer.
26455375 Oseltamivir activity against avian influenza H9N2 strain with different point mutations in their neuraminidase.
26185093 2015 Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia.
26086247 2015 Uncoupling of Elastin Complex Receptor during In Vitro Aging Is Related to Modifications in Its Intrinsic Sialidase Activity and the Subsequent Lactosylceramide Production.
25963144 2015 NEU1 Sialidase Regulates Membrane-tethered Mucin (MUC1) Ectodomain Adhesiveness for Pseudomonas aeruginosa and Decoy Receptor Release.
25925251 2015 Muc1 is protective during kidney ischemia-reperfusion injury.
25600812 2015 Biochemical and molecular characterization of novel mutations in GLB1 and NEU1 in patient cells with lysosomal storage disorders.
25566667 2014 [Glycoprotein sialylation and NEU1 and ST6GAL1 expressions in erythremia].
24808020 2014 Expanding sialidosis spectrum by genome-wide screening: NEU1 mutations in adult-onset myoclonus.
24583283 2014 A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes.
24550400 2014 NEU1 sialidase regulates the sialylation state of CD31 and disrupts CD31-driven capillary-like tube formation in human lung microvascular endothelia.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23391804 2012 Novel mutations in the neuraminidase-1 (NEU1) gene in two patients of sialidosis in India.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23291686 2013 Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
22989879 2012 Sialidases on mammalian sperm mediate deciduous sialylation during capacitation.
22903576 2013 Identification of lysosomal sialidase NEU1 and plasma membrane sialidase NEU3 in human erythrocytes.
22403397 2012 NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia: NEU1 restrains endothelial cell migration, whereas NEU3 does not.
22247545 2012 NEU1 sialidase expressed in human airway epithelia regulates epidermal growth factor receptor (EGFR) and MUC1 protein signaling.
21928149 2011 Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors.
21873432 2011 Neu1 sialidase and matrix metalloproteinase-9 cross-talk is essential for Toll-like receptor activation and cellular signaling.
21551251 2011 Endogenous PMN sialidase activity exposes activation epitope on CD11b/CD18 which enhances its binding interaction with ICAM-1.
21269460 2011 Initial characterization of the human central proteome.
21103358 2010 Elastin peptides signaling relies on neuraminidase-1-dependent lactosylceramide generation.
19851445 2009 High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions.
19686243 2009 Sialidase occurs in both membranes of the nuclear envelope and hydrolyzes endogenous GD1a.
19666471 2009 Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization.
19568825 2009 Type II sialidosis: review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients.
19473359 2009 A longitudinal study of Taiwanese sialidosis type 1: an insight into the concept of cherry-red spot myoclonus syndrome.
19199708 2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19151752 2009 Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin beta4.
18772331 2008 Neuraminidase-1, a subunit of the cell surface elastin receptor, desialylates and functionally inactivates adjacent receptors interacting with the mitogenic growth factors PDGF-BB and IGF-2.
18651674 2008 Human sialidase as a cancer marker.
18606142 2008 Neuraminidase 1 is a negative regulator of lysosomal exocytosis.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17562335 2007 Menstrual cycle-related sialidase activity of the female cervical mucus is associated with exosome-like vesicles.
17480010 2007 Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy.
17028199 2007 Sialidase expression in activated human T lymphocytes influences production of IFN-gamma.
16835219 2006 Monocyte differentiation up-regulates the expression of the lysosomal sialidase, Neu1, and triggers its targeting to the plasma membrane via major histocompatibility complex class II-positive compartments.
16538002 2006 Elastogenesis in cultured dermal fibroblasts from patients with lysosomal beta-galactosidase, protective protein/cathepsin A and neuraminidase-1 deficiencies.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16314420 2006 Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly.
16094384 2005 Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry.
15885103 2005 Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15213228 2004 Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells.
15024131 2004 Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant.
14695530 2004 Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression.
14656967 2003 Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse.
14517945 2003 Molecular pathology of NEU1 gene in sialidosis.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12067718 2002 Identification of a CTL4/Neu1 fusion transcript in a sialidosis patient.
11829139 2002 Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes.
11702224 2001 Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.
11571282 2001 Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail.
11470272 2001 Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient.
11279074 2001 Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex.
11063730 2000 Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis.
10944856 2000 Molecular and structural studies of Japanese patients with sialidosis type 1.
10767332 2000 Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex.
9501080 1998 Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A.
9480870 1998 Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation.
9054950 1997 Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis.
9020182 1997 Identification of a sialidase encoded in the human major histocompatibility complex.
8985184 1996 Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis.
8910459 1996 Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate.
8312369 1994 The biochemistry and clinical features of galactosialidosis.
3922758 1985 Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein.
3102233 1987 Purification and partial characterization of lysosomal neuraminidase from human placenta.