The protein encoded by this gene belongs to a family of glycohydrolytic enzymes, which remove terminal sialic acid residues from various sialo derivatives, such as glycoproteins, glycolipids, oligosaccharides, and gangliosides. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2009] See more...

Aliases for NEU4 Gene

Aliases for NEU4 Gene

  • Neuraminidase 4 2 3 5
  • N-Acetyl-Alpha-Neuraminidase 4 3 4
  • Neuraminidase 4 (Sialidase) 2 3
  • Sialidase-4 3 4
  • EC 3.2.1.18 4 51
  • Sialidase 4 2
  • NEU4 5

External Ids for NEU4 Gene

Previous GeneCards Identifiers for NEU4 Gene

  • GC02M238777
  • GC02M239447
  • GC02P242770
  • GC02P243037
  • GC02P243072
  • GC02P242472
  • GC02P242437
  • GC02P242400
  • GC02P234501
  • GC02P242749

Summaries for NEU4 Gene

Entrez Gene Summary for NEU4 Gene

  • The protein encoded by this gene belongs to a family of glycohydrolytic enzymes, which remove terminal sialic acid residues from various sialo derivatives, such as glycoproteins, glycolipids, oligosaccharides, and gangliosides. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2009]

GeneCards Summary for NEU4 Gene

NEU4 (Neuraminidase 4) is a Protein Coding gene. Diseases associated with NEU4 include Galactosialidosis and Glycoproteinosis. Among its related pathways are Transport to the Golgi and subsequent modification and Other glycan degradation. Gene Ontology (GO) annotations related to this gene include exo-alpha-(2->3)-sialidase activity and exo-alpha-(2->8)-sialidase activity. An important paralog of this gene is NEU3.

UniProtKB/Swiss-Prot Summary for NEU4 Gene

  • May function in lysosomal catabolism of sialylated glycoconjugates. Has sialidase activity towards synthetic substrates, such as 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4-MU-NANA or 4MU-NeuAc). Has a broad substrate specificity being active on glycoproteins, oligosaccharides and sialylated glycolipids.

Gene Wiki entry for NEU4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NEU4 Gene

Genomics for NEU4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NEU4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NEU4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NEU4

Top Transcription factor binding sites by QIAGEN in the NEU4 gene promoter:
  • AML1a
  • AP-4
  • CREB
  • deltaCREB
  • E47
  • HEN1
  • LCR-F1
  • Olf-1
  • RFX1
  • RP58

Genomic Locations for NEU4 Gene

Genomic Locations for NEU4 Gene
chr2:241,808,825-241,817,413
(GRCh38/hg38)
Size:
8,589 bases
Orientation:
Plus strand
chr2:242,749,920-242,758,739
(GRCh37/hg19)
Size:
8,820 bases
Orientation:
Plus strand

Genomic View for NEU4 Gene

Genes around NEU4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NEU4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NEU4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NEU4 Gene

Proteins for NEU4 Gene

  • Protein details for NEU4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WWR8-NEUR4_HUMAN
    Recommended name:
    Sialidase-4
    Protein Accession:
    Q8WWR8
    Secondary Accessions:
    • A8K056
    • J3KNJ5
    • Q96D64

    Protein attributes for NEU4 Gene

    Size:
    484 amino acids
    Molecular mass:
    51572 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAP34475.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for NEU4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NEU4 Gene

Selected DME Specific Peptides for NEU4 Gene

Q8WWR8:
  • HRSMNPCP
  • TFAVGPGH

Post-translational modifications for NEU4 Gene

  • According to PubMed:15213228, phosphorylation of mannose residues may ensure efficient transport of isoform 2 to the lysosomes via the mannose 6-phosphate receptor.
  • Isoform 2 is glycosylated.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for NEU4 Gene

Gene Families for NEU4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for NEU4 Gene

Suggested Antigen Peptide Sequences for NEU4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ54457, highly similar to Sialidase-4 (EC 3.2.1.18) (B3KR54_HUMAN)
  • N-acetyl-alpha-neuraminidase 4 (NEUR4_HUMAN)
  • Sialidase 4 (Q3KR05_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8WWR8

UniProtKB/Swiss-Prot:

NEUR4_HUMAN :
  • Belongs to the glycosyl hydrolase 33 family.
Family:
  • Belongs to the glycosyl hydrolase 33 family.
genes like me logo Genes that share domains with NEU4: view

Function for NEU4 Gene

Molecular function for NEU4 Gene

UniProtKB/Swiss-Prot Function:
May function in lysosomal catabolism of sialylated glycoconjugates. Has sialidase activity towards synthetic substrates, such as 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4-MU-NANA or 4MU-NeuAc). Has a broad substrate specificity being active on glycoproteins, oligosaccharides and sialylated glycolipids.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.; EC=3.2.1.18; Evidence={ECO:0000269|PubMed:15213228};.
UniProtKB/Swiss-Prot Induction:
Down-regulated during monocyte to macrophage differentiation.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Optimum pH is 3.2.;

Enzyme Numbers (IUBMB) for NEU4 Gene

Phenotypes From GWAS Catalog for NEU4 Gene

Gene Ontology (GO) - Molecular Function for NEU4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004308 exo-alpha-sialidase activity IEA,IDA 14962670
GO:0005515 protein binding IPI 16189514
GO:0016787 hydrolase activity IEA --
GO:0016798 hydrolase activity, acting on glycosyl bonds IEA --
GO:0052794 exo-alpha-(2->3)-sialidase activity IEA --
genes like me logo Genes that share ontologies with NEU4: view
genes like me logo Genes that share phenotypes with NEU4: view

Animal Models for NEU4 Gene

MGI Knock Outs for NEU4:
  • Neu4 Neu4<tm1Avps>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NEU4

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NEU4 Gene

Localization for NEU4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NEU4 Gene

[Isoform 1]: Membrane. Peripheral membrane protein.
[Isoform 2]: Lysosome lumen. Note=According to PubMed:15213228, isoform 2 is soluble, N-glycosylated and found in the lumen of lysosomes. However, no signal sequence nor N-glycosylation site is predicted from the sequence.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NEU4 gene
Compartment Confidence
lysosome 5
mitochondrion 3
plasma membrane 2
nucleus 2
cytosol 2
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for NEU4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005764 NOT lysosome IBA,IDA 14962670
GO:0016020 membrane IBA 21873635
GO:0019866 organelle inner membrane IDA 14962670
GO:0043202 lysosomal lumen TAS --
genes like me logo Genes that share ontologies with NEU4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NEU4 Gene

Pathways & Interactions for NEU4 Gene

genes like me logo Genes that share pathways with NEU4: view

Gene Ontology (GO) - Biological Process for NEU4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006516 glycoprotein catabolic process IDA 15213228
GO:0006629 lipid metabolic process IEA --
GO:0006687 glycosphingolipid metabolic process TAS --
GO:0006689 ganglioside catabolic process IBA,IDA 15213228
genes like me logo Genes that share ontologies with NEU4: view

No data available for SIGNOR curated interactions for NEU4 Gene

Drugs & Compounds for NEU4 Gene

(2) Drugs for NEU4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Aceneuramic acid Investigational Pharma 0

(56) Additional Compounds for NEU4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Galactosylceramide (d18:1/16:0)
  • a-GalCer
  • alpha-GalCer
  • Cerebroside
  • D-Galactosyl-N-acylsphingosine
  • D-Galactosylceramide
Galactosylceramide (d18:1/18:0)
  • a-GalCer
  • alpha-GalCer
  • Cerebroside
  • D-Galactosyl-N-acylsphingosine
  • D-Galactosylceramide
Galactosylceramide (d18:1/18:1(9Z))
  • a-GalCer
  • alpha-GalCer
  • Cerebroside
  • D-Galactosyl-N-acylsphingosine
  • D-Galactosylceramide
Galactosylceramide (d18:1/20:0)
  • a-GalCer
  • alpha-GalCer
  • Cerebroside
  • D-Galactosyl-N-acylsphingosine
  • D-Galactosylceramide
Galactosylceramide (d18:1/22:0)
  • a-GalCer
  • alpha-GalCer
  • Cerebroside
  • D-Galactosyl-N-acylsphingosine
  • D-Galactosylceramide
genes like me logo Genes that share compounds with NEU4: view

Transcripts for NEU4 Gene

mRNA/cDNA for NEU4 Gene

5 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
17 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NEU4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NEU4 Gene

No ASD Table

Relevant External Links for NEU4 Gene

GeneLoc Exon Structure for
NEU4

Expression for NEU4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NEU4 Gene

mRNA differential expression in normal tissues according to GTEx for NEU4 Gene

This gene is overexpressed in Liver (x14.8) and Colon - Transverse (x6.7).

Protein differential expression in normal tissues from HIPED for NEU4 Gene

This gene is overexpressed in Liver, secretome (68.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NEU4 Gene



Protein tissue co-expression partners for NEU4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NEU4

SOURCE GeneReport for Unigene cluster for NEU4 Gene:

Hs.551747

mRNA Expression by UniProt/SwissProt for NEU4 Gene:

Q8WWR8-NEUR4_HUMAN
Tissue specificity: Ubiquitous with higher expression in heart, skeletal muscle, liver and placenta.

Evidence on tissue expression from TISSUES for NEU4 Gene

  • Nervous system(3.8)
  • Intestine(2.2)
genes like me logo Genes that share expression patterns with NEU4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for NEU4 Gene

Orthologs for NEU4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NEU4 Gene

Organism Taxonomy Gene Similarity Type Details
Cow
(Bos Taurus)
Mammalia NEU4 30 31
  • 80.66 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Neu4 30 17 31
  • 74.83 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Neu4 30
  • 74.81 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia NEU4 31
  • 59 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NEU4 31
  • 52 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NEU4 30 31
  • 66.06 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NEU4 31
  • 46 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100486976 30
  • 56.25 (n)
Zebrafish
(Danio rerio)
Actinopterygii neu4 30 31
  • 55.13 (n)
OneToOne
Species where no ortholog for NEU4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for NEU4 Gene

ENSEMBL:
Gene Tree for NEU4 (if available)
TreeFam:
Gene Tree for NEU4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NEU4: view image

Paralogs for NEU4 Gene

Paralogs for NEU4 Gene

(2) SIMAP similar genes for NEU4 Gene using alignment to 11 proteins:

  • NEUR4_HUMAN
  • B3KR54_HUMAN
  • C9IZG9_HUMAN
  • C9J295_HUMAN
  • C9J2R4_HUMAN
  • C9J2V4_HUMAN
  • C9J5X2_HUMAN
  • C9JEA3_HUMAN
  • C9JRN9_HUMAN
  • F8WE58_HUMAN
  • Q3KR05_HUMAN
genes like me logo Genes that share paralogs with NEU4: view

Variants for NEU4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NEU4 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs11545301 - p.Gly301Arg

Additional dbSNP identifiers (rs#s) for NEU4 Gene

Structural Variations from Database of Genomic Variants (DGV) for NEU4 Gene

Variant ID Type Subtype PubMed ID
dgv165e55 CNV loss 17911159
dgv4200n100 CNV loss 25217958
dgv4201n100 CNV gain 25217958
esv2664751 CNV deletion 23128226
esv4746 CNV loss 18987735
esv989515 CNV insertion 20482838
nsv1002941 CNV gain 25217958
nsv1006733 CNV gain 25217958
nsv10232 CNV gain+loss 18304495
nsv470533 CNV loss 18288195
nsv584982 CNV loss 21841781
nsv584991 CNV loss 21841781
nsv584996 CNV gain 21841781
nsv955301 CNV deletion 24416366
nsv997984 CNV gain 25217958

Variation tolerance for NEU4 Gene

Residual Variation Intolerance Score: 98.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.39; 63.62% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NEU4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NEU4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NEU4 Gene

Disorders for NEU4 Gene

MalaCards: The human disease database

(7) MalaCards diseases for NEU4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
galactosialidosis
  • gsl
glycoproteinosis
  • mucolipidosis i
gm2-gangliosidosis, ab variant
  • hexosaminidase activator deficiency
charcot-marie-tooth disease, axonal, type 2v
  • cmt2v
epileptic encephalopathy, early infantile, 15
  • eiee15
- elite association - COSMIC cancer census association via MalaCards
Search NEU4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with NEU4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NEU4 Gene

Publications for NEU4 Gene

  1. Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages. (PMID: 15885103) Stamatos NM … Pshezhetsky AV (The FEBS journal 2005) 3 4 23
  2. Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family. (PMID: 14962670) Monti E … Borsani G (Genomics 2004) 3 4 23
  3. Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. (PMID: 15213228) Seyrantepe V … Pshezhetsky AV (The Journal of biological chemistry 2004) 3 4 23
  4. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for NEU4 Gene

Sources for NEU4 Gene