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NEU3

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Summary

NEU3 (neuraminidase 3, HGNC:7760) is a protein-coding gene on chromosome 11q13.4, encoding Sialidase-3 (Q9UQ49). Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides.

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.

Source: NCBI Gene 10825 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 84 total
  • Druggable target: yes — 1 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_006656

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7760
Approved symbolNEU3
Nameneuraminidase 3
Location11q13.4
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000162139
Ensembl biotypeprotein_coding
OMIM604617
Entrez10825

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000294064, ENST00000526068, ENST00000529024, ENST00000531509, ENST00000531619, ENST00000532963, ENST00000534628, ENST00000907442

RefSeq mRNA: 9 — MANE Select: NM_006656 NM_001367860, NM_001367861, NM_001367862, NM_001367863, NM_001367864, NM_001367865, NM_001367866, NM_001367867, NM_006656

CCDS: CCDS44682, CCDS91536, CCDS91537, CCDS91538, CCDS91539

Canonical transcript exons

ENST00000294064 — 3 exons

ExonStartEnd
ENSE000010629237500541375010907
ENSE000011535547498893374989154
ENSE000036202057499450974994720

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 89.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6550 / max 181.9515, expressed in 1803 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
11586410.75931786
1158620.5547284
1158600.3754142
1158610.3316151
2063870.3028117
1158630.2488103
1158650.082318

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
skeletal muscle tissue of rectus abdominisUBERON:000451189.36gold quality
gastrocnemiusUBERON:000138887.43gold quality
muscle of legUBERON:000138387.29gold quality
hindlimb stylopod muscleUBERON:000425285.72gold quality
right adrenal glandUBERON:000123385.44gold quality
left adrenal gland cortexUBERON:003582585.17gold quality
right adrenal gland cortexUBERON:003582785.13gold quality
sural nerveUBERON:001548885.05gold quality
left adrenal glandUBERON:000123484.98gold quality
adrenal cortexUBERON:000123584.70gold quality
biceps brachiiUBERON:000150784.55gold quality
adrenal tissueUBERON:001830384.46gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450284.26gold quality
muscle organUBERON:000163084.07gold quality
adrenal glandUBERON:000236983.71gold quality
right testisUBERON:000453483.44gold quality
left testisUBERON:000453383.41gold quality
monocyteCL:000057683.31gold quality
mononuclear cellCL:000084283.00gold quality
leukocyteCL:000073882.71gold quality
testisUBERON:000047381.61gold quality
tibialis anteriorUBERON:000138580.95silver quality
granulocyteCL:000009480.76gold quality
right lobe of liverUBERON:000111479.40gold quality
apex of heartUBERON:000209878.98gold quality
skeletal muscle tissueUBERON:000113478.27gold quality
deltoidUBERON:000147677.88silver quality
endothelial cellCL:000011577.72silver quality
cortical plateUBERON:000534377.49gold quality
body of pancreasUBERON:000115077.45gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes3.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, SP1, SP3

miRNA regulators (miRDB)

56 targeting NEU3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4673100.0066.641490
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-607799.9968.042299
HSA-MIR-4645-5P99.9865.811284
HSA-MIR-3688-3P99.9772.022834
HSA-MIR-539-5P99.9370.302855
HSA-MIR-612499.8769.783551
HSA-MIR-76599.8468.242442
HSA-MIR-489-3P99.8066.46839
HSA-MIR-4694-3P99.7969.532640
HSA-MIR-11181-3P99.7566.382205
HSA-MIR-1255A99.7468.09744
HSA-MIR-1255B-5P99.7468.16741
HSA-MIR-120099.7170.421838
HSA-MIR-1287-3P99.6366.93492
HSA-MIR-6758-3P99.5767.551078
HSA-MIR-141-5P99.5767.86897
HSA-MIR-17-3P99.5566.771311
HSA-MIR-360999.5269.892587
HSA-MIR-548AH-5P99.5269.732626
HSA-MIR-199A-5P99.5169.711107
HSA-MIR-199B-5P99.5169.741098
HSA-MIR-766-5P99.4767.912225
HSA-MIR-318299.4068.152454
HSA-MIR-425199.4069.193363
HSA-MIR-568399.3668.592083
HSA-MIR-3160-5P99.2869.071938
HSA-MIR-324-3P99.2666.311034
HSA-MIR-125399.1267.081688
HSA-MIR-432499.0470.141569

Literature-anchored findings (GeneRIF, showing 40)

  • Neu3 functions as a caveolin-related signaling molecule within caveolin-rich microdomains (PMID:12011038)
  • up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression (PMID:12149448)
  • NEU3 participates in the control of insulin signaling via modulation of gangliosides and interaction with Grb2 (PMID:12730204)
  • Results show that the sialidase activity of human membrane type ganglioside sialidase (Neu3)is specific for gangliosides. (PMID:15179041)
  • 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. (PMID:15885103)
  • NEU3 differentially regulates cell proliferation through integrin-mediated signalling depending on the extracellular matrix and, on laminins, NEU3 activated molecules often up-regulated in carcinogenesis. (PMID:16241905)
  • NEU3 activated by IL-6 exerts IL-6-mediated signaling, largely via the PI3K/Akt cascade, in a positive feedback manner and contributes to expression of a malignant phenotype in renal cell carcinoma (PMID:16428383)
  • NEU3 is able to mobilize to membrane ruffles in response to growth stimuli and activate the Rac-1 signaling by co-localization with Rac-1, leading to increased cell motility. (PMID:16765317)
  • The activity of Neu3 changed minimally in activated lymphocytes. (PMID:17028199)
  • NEU3 is an important regulator of insulin sensitivity and glucose tolerance. (PMID:17292733)
  • NEU3 may be an essential gene for cancer cell survival. (PMID:17334392)
  • Neu3 is up-regulated in Jurkat cells undergoing etoposide-induced apoptosis (PMID:17827720)
  • NEU3 is markedly up-regulated in many types of cancers including colon and renal carcinomas and suppresses apoptosis of cancer cells. (PMID:18023981)
  • Neu3 degrades membrane sialic acids resulting in downregulation of the PKC/ERKs/p38 MAPK signaling pathway, causing a decrease in CD41b surface antigen expression and inhibition of megakaryocytic differentiation of K562 cells. (PMID:18339327)
  • related to malignancy and may be potential targets for cancer diagnosis and therapy (PMID:18651674)
  • increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of alpha(2-3)-sialidase activity (PMID:18953356)
  • Data show that Neu3 could represent a new potent biomarker in childhood ALL, to assess the efficacy of therapeutic protocols and to rapidly identify an eventual relapse. (PMID:19588508)
  • occurrence of Neu3 in the inner membrane and Neu1 in the outer membrane of the nuclear envelope (PMID:19686243)
  • Truncations at the N- or C-terminus of more than 10 residues abolished enzyme activity. (PMID:20511247)
  • NEU3 expression is diversely regulated by Sp1/Sp3 transcription factors binding to alternative promoters, which might account for multiple modulation of gene expression. (PMID:20518744)
  • observed that trisaccharides with incorporated azide groups in the Neu5Ac residue at either C9 or the N5-Ac position were substrates, and in the case of the N5-azidoacetyl derivative, the activity was superior to that of GM3 (PMID:21675735)
  • These data suggest that NEU3 regulates tumor progression through AR signaling, and thus be a potential tool for diagnosis and therapy of androgen-independent prostate cancer. (PMID:21681193)
  • NEU3 is highly expressed to enhance malignant phenotypes including apoptosis inhibition in malignant melanomas. (PMID:21895867)
  • 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. (PMID:22403397)
  • 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. (PMID:22903576)
  • Data indicate that sialidases Neu1 and Neu3 are present on sperm, and their activity is required for capacitation and zona pellucida binding. (PMID:22989879)
  • NEU3 is a key regulator of the beta1 integrin-recycling pathway and FAK/AKT signaling and demonstrate its crucial role in renal cell carcinomas malignancy. (PMID:23139422)
  • Studies indicate that ganglioside-specific sialidase NEU3 cleaves sialic acids preferentially from gangliosides. (PMID:25408341)
  • The results provide strong evidence that the serum sialidase is, in fact, NEU3, and this subtype may, therefore, be a potential utility for novel diagnosis of human cancers (PMID:25652216)
  • NEU3 promotes anchorage-independent growth and in vivo tumorigenicity. (PMID:25803810)
  • Results indicate an essential contribution of NEU3 to tumorigenic potential through maintenance of stem-like characteristics of colon cancer cells by regulating Wnt signaling at the receptor level. (PMID:25810027)
  • Besides the already reported indirect EGFR activation through GM3, sialidase NEU3 could also play a role on EGFR activation through its desialylation. (PMID:25922362)
  • In the plasma membrane, NEU3 has a role in endocytosis and protein binding at the cell surface. (PMID:26251452)
  • findings identify NEU3 as a participant in head and neck squamous cell carcinoma progression (PMID:26470851)
  • NEU3 possesses the ability to interact with specific proteins, many of which are different in each cell compartment, supporting NEU3 involvement in the cell stress response, protein folding, and intracellular trafficking. (PMID:26987901)
  • The most potent compound tested targeted the human Neu4 isoenzyme, and was able to substantially reduce the rate of cell migration. We found that the lateral mobility of integrins was reduced by treatment of cells with Neu3, suggesting that Neu3 enzyme activity resulted in changes to integrin-co-receptor or integrin-cytoskeleton interactions (PMID:27344026)
  • this finding strongly supports the idea that Neu3 may contain a cytosolic-exposed domain. (PMID:28646141)
  • This first demonstration of sialidase involvement in invasive potential of gliolastoma cells may point to NEU3 as an attractive treatment target of human gliomas (PMID:28760640)
  • effect of overexpression on EGFR downstream pathway activation and TKI targeted therapies sensitivity in non-small cell lung cancer cell lines (PMID:29088281)
  • overexpression of NEU3 in glioblastoma U87MG cells activates the PI3K/Akt signaling pathway resulting in an increased radioresistance capacity and in an improved efficiency of double strand DNA-repair mechanisms after irradiation (PMID:30466783)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_rerioneu3.2ENSDARG00000010047
danio_rerioneu3.3ENSDARG00000058327
danio_rerioneu3.5ENSDARG00000096368
danio_rerioneu3.4ENSDARG00000096381
danio_rerioneu3.1ENSDARG00000096382
mus_musculusNeu3ENSMUSG00000035239
rattus_norvegicusNeu3ENSRNOG00000018106

Paralogs (3): NEU2 (ENSG00000115488), NEU4 (ENSG00000204099), NEU1 (ENSG00000204386)

Protein

Protein identifiers

Sialidase-3 — Q9UQ49 (reviewed: Q9UQ49)

Alternative names: Ganglioside sialidasedis, Membrane sialidase, N-acetyl-alpha-neuraminidase 3

All UniProt accessions (5): Q9UQ49, E9PI40, E9PMZ3, E9PNK1, E9PR25

UniProt curated annotations — full annotation on UniProt →

Function. Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides. Displays high catalytic efficiency for gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3. Plays a role in the regulation of transmembrane signaling through the modulation of ganglioside content of the lipid bilayer and by direct interaction with signaling receptors, such as EGFR. Desialylates EGFR and activates downstream signaling in proliferating cells. Contributes to clathrin-mediated endocytosis by regulating sorting of endocytosed receptors to early and recycling endosomes.

Subunit / interactions. Interacts with CAV1; this interaction enhances NEU3 sialidase activity within caveola. Interacts with EGFR; this interaction mediates desialylation of EGFR and enhances downstream signaling.

Subcellular location. Cell membrane. Membrane. Caveola. Early endosome membrane. Recycling endosome membrane. Lysosome membrane.

Tissue specificity. Highly expressed in skeletal muscle, testis, adrenal gland and thymus, followed by pancreas, liver, heart and thymus. Weakly expressed in kidney, placenta, brain and lung.

Post-translational modifications. Palmitoylated; may regulate intracellular trafficking and anchorage to plasma membrane and endomembranes.

Similarity. Belongs to the glycosyl hydrolase 33 family.

Isoforms (2)

UniProt IDNamesCanonical?
Q9UQ49-11yes
Q9UQ49-22

RefSeq proteins (9): NP_001354789, NP_001354790, NP_001354791, NP_001354792, NP_001354793, NP_001354794, NP_001354795, NP_001354796, NP_006647* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR011040SialidaseDomain
IPR026856Sialidase_famFamily
IPR036278Sialidase_sfHomologous_superfamily

Pfam: PF13088

Enzyme classification (BRENDA):

  • EC 3.2.1.18 — exo-alpha-sialidase (BRENDA: 87 organisms, 524 substrates, 467 inhibitors, 232 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

90 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
4-METHYLUMBELLIFERYL ALPHA-D-N-ACETYLNEURAMINIC0.018–3.322
4-METHYLUMBELLIFERYL-ALPHA-D-N-ACETYLNEURAMINIC0.0002–4.922
FETUIN0.0005–6.711
4-METHYLUMBELLIFERYL N-ACETYLNEURAMINIC ACID0.0103–0.56529
SIALYL-ALPHA-2,6-LACTOSE0.13–3.59
2-(4-METHYLUMBELLIFERYL)-ALPHA-D-N-ACETYLNEURAMI0.0063–0.168
SIALYL-ALPHA-2,3-LACTOSE0.1–4.98
ALPHA-SIALYLLACTOSE0.5–3.35
SIALYLLACTOSE0.52–2.385
5-BROMO-4-CHLORO-INDOLYL BETA-D-GALACTOPYRANOSYL0.08–0.1214
GANGLIOSIDE GD1B0.1–0.594
GD1A0.02–1.754
N-ACETYLNEURAMINYLLACTOSE0.78–34
2’-(4-METHYLUMBELLIFERYL)-ALPHA-D-N-ACETYLNEURAM0.028–1.43
4-METHYLUMBELLIFERYL N-ACETYL-ALPHA-D-NEURAMINIC0.06–1.5083

Catalyzed reactions (Rhea), 12 shown:

  • a ganglioside GT1b + H2O = a ganglioside GD1b + N-acetylneuraminate (RHEA:47828)
  • a ganglioside GD1a + H2O = a ganglioside GM1 + N-acetylneuraminate (RHEA:47832)
  • a ganglioside GD1a (d18:1(4E)) + H2O = a ganglioside GM1 (d18:1(4E)) + N-acetylneuraminate (RHEA:47856)
  • a ganglioside GM1 + H2O = a ganglioside GA1 + N-acetylneuraminate (RHEA:47872)
  • a ganglioside GD1b + H2O = a ganglioside GM1 + N-acetylneuraminate (RHEA:47876)
  • a ganglioside GM3 (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + N-acetylneuraminate (RHEA:47900)
  • a ganglioside GD1b (d18:1(4E)) + H2O = a ganglioside GM1 (d18:1(4E)) + N-acetylneuraminate (RHEA:48064)
  • a ganglioside GM2 (d18:1(4E)) + H2O = a ganglioside GA2 (d18:1(4E)) + N-acetylneuraminate (RHEA:48068)
  • a ganglioside GM1 (d18:1(4E)) + H2O = a ganglioside GA1 (d18:1(4E)) + N-acetylneuraminate (RHEA:48072)
  • a ganglioside GD3 + H2O = a ganglioside GM3 + N-acetylneuraminate (RHEA:48120)
  • a ganglioside GD3 (d18:1(4E)) + H2O = a ganglioside GM3 (d18:1(4E)) + N-acetylneuraminate (RHEA:48124)
  • a ganglioside GM3 + H2O = a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + N-acetylneuraminate (RHEA:48136)

UniProt features (36 total): mutagenesis site 16, binding site 7, repeat 3, active site 3, chain 1, modified residue 1, splice variant 1, sequence variant 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9UQ49-F187.260.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 50 (proton acceptor); 370 (nucleophile); 387

Ligand- & substrate-binding residues (7): 25; 45; 179; 181; 225; 245; 340

Post-translational modifications (1): 313

Mutagenesis-validated functional residues (16):

PositionPhenotype
25loss of enzyme activity.
45loss of enzyme activity.
50nearly abolishes enzyme activity.
51decreases enzyme activity.
88markedly decreases enzyme activity.
107markedly decreases enzyme activity.
114decreases enzyme activity.
162markedly decreases enzyme activity.
179loss of enzyme activity.
181markedly decreases the recruitment within caveola.
181nearly abolishes enzyme activity.
187decreases the recruitment within caveola.
225loss of enzyme activity.
245loss of enzyme activity.
340loss of enzyme activity.
370loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

IDPathway
R-HSA-4085001Sialic acid metabolism
R-HSA-9840310Glycosphingolipid catabolism
R-HSA-1430728Metabolism
R-HSA-1660662Glycosphingolipid metabolism
R-HSA-392499Metabolism of proteins
R-HSA-428157Sphingolipid metabolism
R-HSA-446193Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203Asparagine N-linked glycosylation
R-HSA-446219Synthesis of substrates in N-glycan biosythesis
R-HSA-556833Metabolism of lipids
R-HSA-597592Post-translational protein modification

MSigDB gene sets: 159 (showing top): GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOCC_VACUOLAR_MEMBRANE, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, chr11q13, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_GLYCOLIPID_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (8): carbohydrate metabolic process (GO:0005975), ganglioside catabolic process (GO:0006689), oligosaccharide catabolic process (GO:0009313), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), glycosphingolipid catabolic process (GO:0046479), negative regulation of clathrin-dependent endocytosis (GO:1900186), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (5): exo-alpha-sialidase activity (GO:0004308), alpha-sialidase activity (GO:0016997), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (9): cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), caveola (GO:0005901), membrane (GO:0016020), early endosome membrane (GO:0031901), recycling endosome membrane (GO:0055038), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-9 pathways:

CategoryPathways
Synthesis of substrates in N-glycan biosythesis1
Glycosphingolipid metabolism1
Sphingolipid metabolism1
Metabolism of lipids1
Asparagine N-linked glycosylation1
Post-translational protein modification1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein1
Metabolism1
Metabolism of proteins1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
primary metabolic process2
cellular anatomical structure2
endosome membrane2
ganglioside metabolic process1
glycosphingolipid catabolic process1
ceramide catabolic process1
oligosaccharide metabolic process1
carbohydrate catabolic process1
epidermal growth factor receptor signaling pathway1
regulation of epidermal growth factor receptor signaling pathway1
positive regulation of ERBB signaling pathway1
glycosphingolipid metabolic process1
glycolipid catabolic process1
sphingolipid catabolic process1
negative regulation of receptor-mediated endocytosis1
clathrin-dependent endocytosis1
regulation of clathrin-dependent endocytosis1
lipid metabolic process1
catabolic process1
alpha-sialidase activity1
hydrolase activity, hydrolyzing O-glycosyl compounds1
binding1
catalytic activity1
hydrolase activity1
intracellular anatomical structure1
lytic vacuole1
lysosome1
lytic vacuole membrane1
membrane1
cell periphery1
plasma membrane raft1
early endosome1
recycling endosome1
endomembrane system1
cytoplasmic vesicle1

Protein interactions and networks

STRING

884 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NEU3MCOLN1Q9GZU1770
NEU3CTSAP10619584
NEU3GASTP01350549
NEU3ST3GAL3Q11203545
NEU3EGFRP00533509
NEU3ST6GAL1P15907507
NEU3ST3GAL2Q16842505
NEU3NEU2Q9Y3R4502
NEU3NEU1Q99519488
NEU3ST3GAL1Q11201480
NEU3ST3GAL4Q11206478
NEU3ST3GAL5Q9UNP4465
NEU3ST3GAL6Q9Y274437
NEU3ST8SIA1Q92185433
NEU3GLB1P16278424

IntAct

18 interactions, top by confidence:

ABTypeScore
KLK5DENND11psi-mi:“MI:0914”(association)0.640
PLA2G10CHEK1psi-mi:“MI:0914”(association)0.530
ALOX5DDHD2psi-mi:“MI:0914”(association)0.530
NTRK3FAM171A2psi-mi:“MI:0914”(association)0.480
LY86TMEM131Lpsi-mi:“MI:0914”(association)0.350
KLHL14ARHGAP32psi-mi:“MI:0914”(association)0.350
TUBBpsi-mi:“MI:0914”(association)0.350
F12psi-mi:“MI:0914”(association)0.350
EFNA2MGST3psi-mi:“MI:0914”(association)0.350
IL12RB1ZNF185psi-mi:“MI:0914”(association)0.350
KLK5LRP5psi-mi:“MI:0914”(association)0.350
CDK20RPS6KA4psi-mi:“MI:0914”(association)0.350
AFG2AESYT2psi-mi:“MI:0914”(association)0.350
AFG2BMMP24OSpsi-mi:“MI:0914”(association)0.350
DNAJA2ENC1psi-mi:“MI:0914”(association)0.350

BioGRID (27): NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-RNA), NEU3 (Affinity Capture-Western), GRB2 (Affinity Capture-Western), NEU3 (Affinity Capture-Western), NEU3 (Affinity Capture-RNA), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), NEU3 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A5PJN5, A6NFQ2, A6QLU7, A6QQ07, A6QQV6, A7Z052, O95479, O97859, P16452, P49753, P56201, Q32N48, Q32PY6, Q3U3W5, Q3UY23, Q5HZW3, Q5R8R3, Q5RJG7, Q5S6T3, Q5U4E8, Q5XFW6, Q5XIA3, Q64393, Q64627, Q68G58, Q865R1, Q8BZL1, Q8BZW8, Q8C0L6, Q8CAE2, Q8CFX1, Q8NFF5, Q8VDG7, Q8WWR8, Q921K8, Q922X9, Q99ME2, Q99MI9, Q99PW5

Diamond homologs: D4B4P1, O97859, P62575, P62576, Q4WQS0, Q64393, Q64627, Q8BZL1, Q8WWR8, Q99PW5, Q9JMH3, Q9JMH7, Q9UQ49, Q9Y3R4, I1S2N3, O35657, P0DTR4, P29767, Q0TR53, Q27701, Q2MGH6, Q8DR60, Q8XL08, Q99PW3, A5PF10, A6BMK7, P15698, P29768, Q5RAF4, Q99519, P31206

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

84 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance76
Likely benign4
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

916 predictions. Top by Δscore:

VariantEffectΔscore
11:74994658:A:Tdonor_gain1.0000
11:74994662:A:Gdonor_gain1.0000
11:74989152:CAGGT:Cdonor_loss0.9900
11:74989153:AGGTG:Adonor_loss0.9900
11:74989154:GG:Gdonor_loss0.9900
11:74989155:G:Adonor_loss0.9900
11:74989156:T:Gdonor_loss0.9900
11:74994667:G:GTdonor_gain0.9900
11:74994695:GGT:Gdonor_gain0.9900
11:75005411:AGTGG:Aacceptor_gain0.9900
11:75005412:GTGGG:Gacceptor_gain0.9900
11:75005565:C:Tdonor_gain0.9900
11:75005411:AGT:Aacceptor_gain0.9800
11:75005412:GTG:Gacceptor_gain0.9800
11:75005602:G:GTdonor_gain0.9800
11:74994562:G:GTdonor_gain0.9700
11:74994711:G:GGdonor_gain0.9700
11:74997961:G:GGdonor_gain0.9700
11:75005411:A:AGacceptor_gain0.9700
11:75005411:AGTG:Aacceptor_gain0.9700
11:75005412:G:GGacceptor_gain0.9700
11:75005412:GTGG:Gacceptor_gain0.9700
11:74994508:GA:Gacceptor_gain0.9600
11:74994685:C:Gdonor_gain0.9600
11:74994691:C:Tdonor_gain0.9500
11:74994710:A:AGdonor_gain0.9500
11:75005412:GT:Gacceptor_gain0.9500
11:75006784:A:Tdonor_gain0.9500
11:74994506:CAG:Cacceptor_gain0.9400
11:74994507:A:AGacceptor_gain0.9400

AlphaMissense

3009 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000019795 (11:75003538 A>G), RS1000084599 (11:75005400 TCTC>T), RS1000119955 (11:74996125 G>A), RS1000152639 (11:74987745 G>A), RS1000185936 (11:74988049 A>G,T), RS1000360432 (11:74981059 A>G), RS1000578012 (11:75020327 G>A,C), RS1000626522 (11:75014851 G>A), RS1000713139 (11:75016137 T>C), RS1000769083 (11:75007438 G>T), RS1000879908 (11:74999885 C>T), RS1000990529 (11:74982795 G>A), RS1001008441 (11:74993360 C>A,T), RS1001039579 (11:74993488 G>A), RS1001061267 (11:75015758 C>T)

Disease associations

OMIM: gene MIM:604617 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3046 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,528 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL222813ZANAMIVIR442,528

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs7115499NEU30.000

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(triazol-1-yl)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acidIC5070000 nMUS-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE

ChEMBL bioactivities

67 potent at pChembl≥5 of 131 total, top 40 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.55Ki280nMCHEMBL4076203
6.50Ki320nMCHEMBL4099818
6.44Ki360nMCHEMBL4099818
6.24IC50580nMCHEMBL4099818
6.21IC50610nMCHEMBL4064112
6.21Ki620nMZANAMIVIR
6.16IC50700nMCHEMBL4076203
6.00IC501000nMCHEMBL4062382
5.96IC501100nMCHEMBL4071732
5.80Ki1600nMNEU5AC2EN
5.66Ki2200nMNEU5AC2EN
5.62IC502400nMNEU5AC2EN
5.60IC502500nMCHEMBL55440
5.54IC502900nMCHEMBL4454422
5.48IC503300nMCHEMBL4069646
5.42IC503800nMCHEMBL4099818
5.41IC503900nMCHEMBL4745230
5.40IC504000nMZANAMIVIR
5.36IC504400nMCHEMBL1289862
5.36IC504400nMCHEMBL4467946
5.34IC504600nMCHEMBL1289428
5.33IC504700nMCHEMBL1289862
5.30IC505000nMCHEMBL3588980
5.30IC505000nMCHEMBL336080
5.26IC505500nMCHEMBL1289649
5.26IC505500nMCHEMBL4076383
5.23IC505900nMCHEMBL4060974
5.20IC506300nMNEU5AC2EN
5.17IC506700nMCHEMBL4285561
5.17IC506800nMZANAMIVIR
5.16IC507000nMZANAMIVIR
5.15IC507100nMCHEMBL4277321
5.14IC507200nMCHEMBL4279510
5.11IC507700nMNEU5AC2EN
5.10Ki8000nMCHEMBL2325811
5.09IC508170nMZANAMIVIR
5.09IC508200nMCHEMBL4089157
5.06IC508700nMCHEMBL4084911
5.05IC509000nMCHEMBL338909
5.03IC509300nMCHEMBL4080360

PubChem BioAssay actives

43 with measured affinity, of 310 total; 24 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenylphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490012: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured every minute for 30 mins by fluorescence based assayki0.2800uM
(2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenylphenyl)triazol-1-yl]propyl]-3,4-dihydro-2H-pyran-6-carboxylic acid1490012: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured every minute for 30 mins by fluorescence based assayki0.3200uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-(4-carboxyphenyl)triazol-1-yl]-1,2-dihydroxypropyl]-4-(diaminomethylideneamino)-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic500.6100uM
Zanamivir1405018: Inhibition of MBP-fused recombinant human neuraminidase 3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured every 1 min for 30 mins by fluorescence analysiski0.6200uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenoxyphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic501.0000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-(4-carboxyphenyl)triazol-1-yl]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic501.1000uM
(2R,3R,4S)-3-acetamido-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid1405018: Inhibition of MBP-fused recombinant human neuraminidase 3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured every 1 min for 30 mins by fluorescence analysiski1.6000uM
4-acetamido-3-(diaminomethylideneamino)benzoic acid147479: In vitro inhibitory activity against H1N9 strain of Influenza Neuraminidase (membrane)ic502.5000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-[4-(trifluoromethyl)phenyl]triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic503.3000uM
(2R,3R,4S)-4-hydroxy-3-[(2,2,2-trifluoroacetyl)amino]-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid1720574: Inhibition of human NEU3 expressed in HEK293A cells as substrate incubated for 1 hr by spectrofluorometric analysisic503.9000uM
(2R,3R,4S)-3-[(2-azidoacetyl)amino]-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid1415003: Inhibition of N-terminal MBP-fused human NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assayic504.4000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(4-phenyltriazol-1-yl)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid748618: Inhibition of human NEU3 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysisic504.6000uM
3-(diaminomethylideneamino)-4-(methylcarbamoyl)benzoic acid147479: In vitro inhibitory activity against H1N9 strain of Influenza Neuraminidase (membrane)ic505.0000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-(4-acetamidophenyl)triazol-1-yl]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic505.5000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(phenoxymethyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid748618: Inhibition of human NEU3 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysisic505.5000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-methoxyphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic505.9000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(4-pentyltriazol-1-yl)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1415003: Inhibition of N-terminal MBP-fused human NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assayic506.7000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[(3-acetamidobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1415003: Inhibition of N-terminal MBP-fused human NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assayic507.1000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[(4-acetamidobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1415003: Inhibition of N-terminal MBP-fused human NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assayic507.2000uM
(2S,3R,4S)-3-acetamido-4-azido-2-[(phenylmethoxyamino)methyl]-3,4-dihydro-2H-pyran-6-carboxylic acid728981: Inhibition of human neuraminidase 3 expressed in Escherichia coli using 4MU-NANA as substrate measured for every 30 seconds for 60 mins by fluorescence assayki8.0000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-methylphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic508.2000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-(4-aminophenyl)triazol-1-yl]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic508.7000uM
3-(diaminomethylideneamino)-4-sulfamoylbenzoic acid147479: In vitro inhibitory activity against H1N9 strain of Influenza Neuraminidase (membrane)ic509.0000uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-[4-(dimethylamino)phenyl]triazol-1-yl]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid1490016: Inhibition of human N-terminal MBP-fused NEU3 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assayic509.3000uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arseniteaffects methylation, increases expression2
Benzo(a)pyrenedecreases methylation, increases expression2
aristolochic acid Iincreases expression1
FR900359decreases phosphorylation1
bisphenol Adecreases expression1
hydroxyhydroquinoneincreases expression1
manganese chlorideincreases abundance, increases expression1
hydroquinoneincreases expression1
catecholincreases expression1
jinfukangaffects cotreatment, increases expression1
Sunitinibdecreases expression1
Arsenic Trioxideincreases expression1
Leflunomidedecreases expression1
Acetaminophenincreases expression1
Caffeineincreases phosphorylation1
Cisplatinaffects cotreatment, increases expression1
Doxorubicindecreases expression1
Estradiolincreases expression1
Manganeseincreases abundance, increases expression1
Urethanedecreases expression1
Okadaic Acidincreases expression1

ChEMBL screening assays

41 unique, capped per target: 41 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1060575BindingInhibition of human NEU3 transiently transfected in HEK293 cells at 1 mM by fluorimetric analysisHuman sialidase inhibitors: design, synthesis, and biological evaluation of 4-acetamido-5-acylamido-2-fluoro benzoic acids. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_E1KVHyCyte HeLa KO-hNEU3Cancer cell lineFemale
CVCL_E2DVHAP1 NEU3 (-)Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot