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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]
Uniprot Accession IDs
Gene Name
Ensembl ID
  • ENST00000294064
  • ENSP00000294064
  • ENSG00000162139
  • ENST00000531509
  • ENSP00000432097

Symbol
  • SIAL3
Illumination Graph
0.8 0.6 0.4 0.2
Knowledge Table
Most Knowledge About
Knowledge Value (0 to 1 scale)
histone modification site profile
0.83
disease perturbation
0.79
pathway
0.73
gene perturbation
0.72
tissue
0.68


Protein Classes
IDG Development Level Summary
Tdark

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:

Pubmed score: 171.9   (req: < 5)
Gene RIFs: 49   (req: <= 3)
Antibodies: 66   (req: <= 50)
Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 171.9   (req: >= 5)
Gene RIFs: 49   (req: > 3)
Antibodies: 66   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9
Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 5
Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0
Expression Data (409 Tissues)
none
JensenLab TISSUES
JensenLab TISSUESGTEx - FemaleGTEx - MaleHPA RNAHPA ProteinHPM ProteinExpression Typemulticellular organismbody properglandgenitourinary systemendocrine glandskeletal systemreproductive systemmusculature of bodymusculaturefemale reproductive systemnervous systemtrunkmale reproductive systeminternal male genitaliachestcentral nervous systembrainheadbreastgonadtestismammary glandviscuskidneyrenal systemhematopoietic systemimmune systemlymphoid tissuelivercardiovascular systeminternal female genitaliaheartintegumentintestinedigestive systemdigestive tractlymph nodebloodlarge intestinerespiratory systemhematopoietic celllungleukocyteovaryspleencolonprostate glandembryonic structureconnective tissuebone marrowuterusepitheliumphagocytemacrophagelymphocyteblood plasmaforebrainmononuclear cellfibroblasttelencephaloncerebral cortexcerebral hemispheremucosaendotheliumneutrophilmonocyteblood vesselT celllobe of cerebral hemispheregranulocyteendothelial celluterine cervixnerveneuronplateletadrenal glandembryocardiac muscle tissueskin of bodybrainstemepithelial cellsmall intestineneckdendritic celllimbic systemvertebral columnB cellspinal corderythrocytelate embryothroatadipose tissueintestinal mucosaglial cellplacentaabdomenpleural fluidzona pellucidaaorta tunica intimathyroid glandduodenumpancreascaecumsecondary oocyteprimary oocytehepatocytereticuloendothelial systemsmooth muscle tissuehippocampal formationtemporal lobecolonic mucosaarterymegakaryocytemouthintestinal epitheliumcapillarygerm layerhematopoietic stem cellepididymisskin epidermisadrenal medullabone marrow cellcerebral hemisphere white mattermyelinsemenentire myelin sheathepidermal cellstromal cellmesodermbronchusmyoblastileumblood serumcerebellumhindbrainmetencephalonperipheral nervous systemskeletal jointexocrine glandfrontal cortexspermfat padvasculaturethymusganglionretinasmooth muscle cellaortaperitoneal cavitycervical mucustunica intimaendometriumforelimbmyocardiumseminal vesicle fluidseminal fluidwhite adipose tissueoocyteduct of salivary glandplasma cellalveolus of lungalveolar sacartery wallendothelial cell of vascular treeurinary bladdervermiform appendixdiencephalonhypothalamustonsilstomachoccipital lobegallbladdernasopharynxrectumchordate pharynxmouth mucosaparietal lobecorpus callosumsaliva-secreting glandcaudate nucleusPurkinje cell layer of cerebellar cortexendometrial stromaendometrium glandular epitheliumesophagus squamous epitheliumfallopian tubehippocampus fimbriarenal glomerulusnephron tubuleoral epitheliumovarian follicleovary stromaparathyroid glandseminal vesicleskeletal muscle tissueskin fibroblastskin 1 - keratinocytesskin 1 - Langerhansskin 1 - melanocytesskin 2 - epidermal cellssoft tissue 1 - chondrocytessoft tissue 2 - chondrocytesred pulp of spleenwhite pulp of spleenglandular cell of stomachLeydig cell region of testisvaginaesophagusB CellsCD4 CellsCD8 Cellspresumptive gutMonocytesNK CellsPlateletsamygdalaangular gyrusanterior cingulate cortexanterior cingulate gyrusanteroventral cochlear nucleusventral funiculus of spinal cordinsular cortexventral anterior nucleus of thalamusarcuate nucleusextrastriate cortexarea postremaprimary visual cortexcentral medial nucleuscerebellar cortexcerebellar nuclear complexwhite matter of cerebellumcervical spinal cordchoroid plexusclaustrum of braincorticomedial nuclear complexcuneate nucleuscuneiform nucleusdentate gyrus of hippocampal formationdorsal cochlear nucleusdorsal funiculus of spinal cordmedullary reticular formationdorsal motor nucleus of vagus nervedorsal raphe nucleusdorsal tegmental nucleusdorsolateral prefrontal cortexmidbrain tegmentumdorsomedial nucleus of hypothalamusprefrontal cortexentorhinal cortexflocculonodular lobefrontal operculumfrontomarginal sulcusfrontopolar cortexfusiform gyrusglobus pallidusgyrus rectushabenulaCA1 field of hippocampusCA2 field of hippocampusCA3 field of hippocampusinferior colliculusinferior frontal gyrusinferior olivary complexinferior parietal cortexinferior temporal gyrusintraparietal sulcuspontine nuclear grouplateral amygdaloid nucleuslateral funiculus of spinal cordlateral geniculate bodylateral hypothalamic areanucleus of lateral lemniscuslateral reticular nucleuslateral parabrachial nucleuslateral nuclear group of thalamuslateral vestibular nucleuslingual gyruslocus ceruleusmammillary bodymedial dorsal nucleus of thalamusmedial geniculate bodymedial superior olivary nucleusmedial parabrachial nucleusperiolivary nucleusmedial vestibular nucleusmedian raphe nucleuscingulate cortexmiddle frontal gyrusmiddle temporal gyrusfacial motor nucleushypoglossal nucleusmotor nucleus of trigeminal nervenucleus of trapezoid bodynucleus accumbensnucleus ambiguusbasal nucleus of telencephalongracile nucleusnucleus of diagonal bandnucleus raphe magnusnucleus raphe obscurusnucleus raphe pallidusreuniens nucleusrhomboidal nucleusnucleus of solitary tractoccipital cortexolfactory entorhinal cortexolfactory tubercleorbitofrontal cortexparacentral lobuleparahippocampal gyrusparamedian reticular nucleusparaventricular nucleus of hypothalamusparietal cortexparietal operculumparieto-insular cortexparieto-occipital sulcustemporoparietal junctionparvocellular reticular nucleuspedunculopontine tegmental nucleuscentral gray substance of midbrainperirhinal cortexperitrigeminal nucleuspiriform cortexpontine raphe nucleuspostcentral gyrusposterior cingulate cortexposterior nucleus of thalamusposteroventral cochlear nucleusprecentral gyrusprecuneus cortexpremotor cortexpreoptic areanucleus preposituspretectal regionprincipal sensory nucleus of trigeminal nervepulvinar nucleusputamenred nucleuscaudal pontine reticular nucleusoral pontine reticular nucleusreticulotegmental nucleusretrosplenial regionseptal nuclear complexsomatosensory cortexcaudal part of spinal trigeminal nucleusinterpolar part of spinal trigeminal nucleusoral part of spinal trigeminal nucleusvestibular nucleusstria terminalissubcallosal areasubcentral gyrus, S2subiculumsubstantia nigrasubthalamic nucleussuperior colliculussuperior frontal gyrussuperior olivary complexsuperior parietal cortexsuperior temporal gyrussuperior vestibular nucleussupplemental motor cortexsupramarginal gyrussupraoptic nucleustemporal cortextemporal polewhite matter of temporal lobetemporo-occipital transitional zonetongueanterior transverse temporal gyrusposterior transverse temporal gyrusventral posterolateral nucleusventral posteromedial nucleus of thalamusventral tegmental areaventral nuclear groupventrolateral medulla, A1-C1 cell groupsventromedial nucleus of hypothalamuscerebellar vermiszona incertapituitary glandsuprapubic skintransverse colontibial nerveC1 segment of cervical spinal cordAmmon's hornouter medulla of kidneysigmoid coloncortex of kidneyright lobe of liverleft ventricle myocardiumgastroesophageal sphincterbody of pancreasectocervixendocervixsubcutaneous adipose tissueesophagus muscularis mucosaanterior lingual glandright atrium auricular regionbreast epitheliumCells - Cultured fibroblastsvenous bloodtibial arterygastrocnemius medialisPeyer's patchlower leg skinupper lobe of left lungcoronary arteryascending aortaomental fat padCells - EBV-transformed lymphocytes
root: immaterial entity (BFO:0000141)
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root: material entity (BFO:0000040)
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Coexpression Data
Tissue Specific Coexpression (277)
Illuminating Dark Proteins using Reactome Pathways.
Brunson et al., bioRxiv : the preprint server for biology, 2023-06-05
Items per page:
5
1 – 5 of 277
Coexpressed Target
Data Source
Tissue
GTEx
Pituitary
GTEx
Pituitary
GTEx
Pituitary
GTEx
Pituitary
GTEx
Pituitary
Cancer Specific Coexpression (56)
Items per page:
5
1 – 5 of 56
Coexpressed Target
Data Source
Cancer Type
TCGA
STAD
TCGA
CHOL
TCGA
CHOL
TCGA
CHOL
TCGA
CHOL
Protein Sequence and Structure
Residue Counts
LSEAGPVKRTQDIFNYHCMW0510152025303540
Protein Sequence
ProtVista Viewer
Related Tools (5)
Target Illumination GWAS Analytics (TIGA)
Thumbnail image for Target Illumination GWAS Analytics (TIGA)
TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.
GENEVA
Thumbnail image for GENEVA
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.
GlyGen
Thumbnail image for GlyGen
GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.
ARCHS4
Thumbnail image for ARCHS4
ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.
Protein-Protein Interactions (63)
1 – 10 of 63
PLA2G10
Tchem
IDG Family:  Enzyme
Novelty:  0.00289317
p_int:  0.905327349
p_ni:  0.094672425
p_wrong:  2.26e-7
Score:  0.178
Data Source:  BioPlex,STRINGDB
ALOX5
Tclin
IDG Family:  Enzyme
Novelty:  0.00062988
p_int:  0.776158586
p_ni:  0.223836312
p_wrong:  0.000005102
Score:  0.188
Data Source:  BioPlex,STRINGDB
GLA
Tclin
IDG Family:  Enzyme
Novelty:  0.00075604
Score:  0.914
Data Source:  STRINGDB
ARSA
Tbio
IDG Family:  Enzyme
Novelty:  0.00469851
Score:  0.913
Data Source:  STRINGDB
GALC
Tbio
IDG Family:  Enzyme
Novelty:  0.00203532
Score:  0.91
Data Source:  STRINGDB
GAL3ST1
Tbio
IDG Family:  Enzyme
Novelty:  0.02939055
Score:  0.908
Data Source:  STRINGDB
UGT8
Tchem
IDG Family:  Enzyme
Novelty:  0.02518383
Score:  0.9
Data Source:  STRINGDB
MCOLN1
Tchem
IDG Family:  IC
Novelty:  0.00442768
Score:  0.75
Data Source:  STRINGDB
ST3GAL3
Tbio
IDG Family:  Enzyme
Novelty:  0.01592595
Score:  0.641
Data Source:  STRINGDB
ST3GAL5
Tbio
IDG Family:  Enzyme
Novelty:  0.01407498
Score:  0.637
Data Source:  STRINGDB
Predicted Interactions
Pathways (14)
Asparagine N-linked glycosylation (R-HSA-446203)
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Details

Click on a row in the table to change the structure displayed.

Items per page:
1 – 5 of 10
Data Source
Name
Explore in Pharos
Explore in Source
Reactome
Asparagine N-linked glycosylation
Reactome
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
Reactome
Glycosphingolipid metabolism
Reactome
Metabolism
Reactome
Metabolism of lipids
Interacting Pathways
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.
Viral Interactions (0)
No viral interactions found
Gene Ontology Terms (12)
Items per page:
5
1 – 5 of 5
GO Term
Evidence
Assigned by
Inferred from Direct Assay (IDA)
MGI
Inferred from Direct Assay (IDA)
UniProtKB
Inferred from Sequence or structural Similarity (ISS)
UniProtKB
Inferred from Sequence or structural Similarity (ISS)
UniProtKB
Inferred from Electronic Annotation (IEA)
UniProtKB-EC
Disease Associations (2)
1 – 2 of 2
Predicted Diseases
No data found
Disease Novelty (TIN-X)
none
1.00000µ100.000µ10.0000m1.00000100.000Novelty1.00000m10.0000m100.000m1.0000010.0000Importance
root: disease (DOID:4)
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GWAS Traits (2)
GWAS Trait
EFO ID
Study Count
SNP Count
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
polyp of colon
1
1
1
20.5
type 2 diabetes mellitus
1
1
1
12.1
none
12.012.513.013.514.014.515.015.516.016.517.017.518.018.519.019.520.020.521.0Mean Rank Score0.00.51.01.52.0Beta Count
Find similar targets by:
IDG Resources
No IDG generated resources found
Orthologs (10)
1 – 5 of 10
Species
Name
Source ID
Gene ID
OMA
EggNOG
Inparanoid
Chimp
neuraminidase 3
VGNC:48937
748654
Macaque
neuraminidase 3
694310
Mouse
MGI:1355305
50877
Rat
RGD:619881
117185
Dog
neuraminidase 3
VGNC:52272
485195
Species
Name
OMA
EggNOG
Inparanoid
Chimp
neuraminidase 3
Macaque
neuraminidase 3
Mouse
Rat
Dog
neuraminidase 3
Publication Statistics
PubMed Score 171.90
PubMed score by year
none
1975198019851990199520002005201020152020Year024681012Score
PubTator Score 78.39
PubTator score by year
none
1970197519801985199019952000200520102015Year02468Score
Publications (61)
Overrepresented Terms from Abstracts 100 terms from up to 100 abstracts, scaled based on the degree of overrepresentation (Fisher's Exact Test p-Value).
NEU3sialidasegangliosidesgangliosidesialidasessialicmembrane-associatedNeu1GM3GD1aglycolipidssialylationGM1Neu4glycoconjugatesplasmaenzymeNEU2ganglioside-specificglycoproteinsneuraminidaseshumanGD3GM2activity-nulldehydro-2-deoxy-N-acetylneuraminicmethylumbelliferyldesialylationdehydro-N-acetylneuraminicmembranesurfaceglycolipiddecreasedeoxy-2contentkeyTSSslactosylceramideMU-NANAcellglycosidasecatabolismcolonacidNeusialyllactosesubstratesGD1benhancedsignalingacidsCOS-1AG1478neuraminidasePPCAactivityprotein/cathepsinremovalhydrolyzingcompositionmarkedlysubstrateleafletresultedEGFRcellsbrieflyterminalfetuinfoundAktHeLaapoptosiscloselysugarpHclustersgrowth
Items per page:
1 – 5 of 61
The extracellular sialidase NEU3 primes neutrophils.
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.
Sialidase NEU3 and its pathological significance.
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.
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.
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.
Abstract: (show)
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.