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NEU4 neuraminidase 4 [ Homo sapiens (human) ]

Gene ID: 129807, updated on 5-Mar-2024

Summary

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Official Symbol
NEU4provided by HGNC
Official Full Name
neuraminidase 4provided by HGNC
Primary source
HGNC:HGNC:21328
See related
Ensembl:ENSG00000204099 MIM:608527; AllianceGenome:HGNC:21328
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
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]
Expression
Biased expression in colon (RPKM 9.5), liver (RPKM 4.5) and 5 other tissues See more
Orthologs
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Genomic context

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See NEU4 in Genome Data Viewer
Location:
2q37.3
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (241809193..241817413)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (242310986..242319206)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (242750288..242758739)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12558 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12559 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17430 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17431 Neighboring gene D-2-hydroxyglutarate dehydrogenase Neighboring gene MPRA-validated peak4107 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242703699-242704312 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242710178-242711090 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242714429-242715049 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242716291-242716911 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242716912-242717532 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242717533-242718152 Neighboring gene galactose-3-O-sulfotransferase 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:242727152-242728351 Neighboring gene CEB1 minisatellite repeat instability region Neighboring gene uncharacterized LOC124905349 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242776389-242776889 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:242784078-242784237 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242784841-242785538 Neighboring gene uncharacterized LOC124905350 Neighboring gene uncharacterized LOC105373977 Neighboring gene programmed cell death 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Sialidase NEU4 is involved in glioblastoma stem cell survival. Silvestri I, et al. Cell Death Dis, 2014 Aug 21. PMID 25144716, Free PMC Article
  2. A proline-rich loop mediates specific functions of human sialidase NEU4 in SK-N-BE neuronal differentiation. Bigi A, et al. Glycobiology, 2013 Dec. PMID 24030392
  3. Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively. Bigi A, et al. Glycobiology, 2010 Feb. PMID 19797320
  4. Integrin-mediated cell migration is blocked by inhibitors of human neuraminidase. Jia F, et al. Biochim Biophys Acta, 2016 Sep. PMID 27344026
  5. Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons. Takahashi K, et al. J Biol Chem, 2012 Apr 27. PMID 22393058, Free PMC Article

See all (29) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Neuraminidase 4 (NEU4): new biological and physiological player.
    Title: Neuraminidase 4 (NEU4): new biological and physiological player.
  2. Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates.
    Title: Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates.
  3. Synergistic activation of the NEU4 promoter by p73 and AP2 in colon cancer cells.
    Title: Synergistic activation of the NEU4 promoter by p73 and AP2 in colon cancer cells.
  4. 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
    Title: Integrin-mediated cell migration is blocked by inhibitors of human neuraminidase.
  5. The silencing or chemical inhibition of NEU4 changes the entire glycosylation pattern of proteins and lipids, making it more similar to that of differentiated GBM cells and drastically reduces GSCs survival.
    Title: Sialidase NEU4 is involved in glioblastoma stem cell survival.
  6. The results demonstrate that the proline-rich region can also enhance cell proliferation and retinoic acid (RA)-induced neuronal differentiation and it is also involved in NEU4 interaction with Akt.
    Title: A proline-rich loop mediates specific functions of human sialidase NEU4 in SK-N-BE neuronal differentiation.
  7. Overexpression of NEU4 is associated with neuroblastoma.
    Title: NEU4L sialidase overexpression promotes β-catenin signaling in neuroblastoma cells, enhancing stem-like malignant cell growth.
  8. NEU4 is involved in regulation of neuronal function by polySia degradation in mammals.
    Title: Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons.
  9. NEU4 plays an important role in control of sialyl Lewis antigen expression and its impairment in colon cancer
    Title: Regulation of sialyl Lewis antigen expression in colon cancer cells by sialidase NEU4.
  10. The NEU4 long form localizes in mitochondria, while the short form is also associated with the endoplasmic reticulum.
    Title: Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ35928, MGC18222, MGC102757

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables exo-alpha-(2->3)-sialidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables exo-alpha-(2->6)-sialidase activity IEA
Inferred from Electronic Annotation
more info
  
enables exo-alpha-(2->8)-sialidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables exo-alpha-sialidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables exo-alpha-sialidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables exo-alpha-sialidase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in ganglioside catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ganglioside catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glycoprotein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of neuron projection development IEA
Inferred from Electronic Annotation
more info
  
involved_in oligosaccharide catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in oligosaccharide catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
  
located_in lysosomal lumen TAS
Traceable Author Statement
more info
  
is_active_in lysosome IBA
Inferred from Biological aspect of Ancestor
more info
  
NOT located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial inner membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrial outer membrane IEA
Inferred from Electronic Annotation
more info
  
located_in neuron projection IEA
Inferred from Electronic Annotation
more info
  
located_in organelle inner membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
sialidase-4
Names
N-acetyl-alpha-neuraminidase 4
neuraminidase 4 (sialidase)
NP_001161071.1
NP_001161072.1
NP_001161073.1
NP_001161074.1
NP_542779.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001167599.3 → NP_001161071.1  sialidase-4 isoform 2

    See identical proteins and their annotated locations for NP_001161071.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate acceptor splice site at one of the coding exons compared to variant 1, resulting in an isoform (2) that is 1 aa longer than isoform 1.
    Source sequence(s)
    AC131097, AK091038, BC063465, DB173219
    Consensus CDS
    CCDS54441.1
    UniProtKB/TrEMBL
    A8K211, Q3KR05
    Related
    ENSP00000320318.6, ENST00000325935.10
    Conserved Domains (1) summary
    cd15482
    Location:23 → 469
    Sialidase_non-viral; Non-viral sialidases

  2. NM_001167600.3 → NP_001161072.1  sialidase-4 isoform 3

    See identical proteins and their annotated locations for NP_001161072.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate exon at the 5' end compared to variant 1, resulting in translation initiation from an in-frame downstream AUG, and an isoform (3, also known as NEU4 short) with a shorter N-terminus compared to isoform 1. Variants 3-5 encode the same isoform.
    Source sequence(s)
    AC131097, AK289421, BC063465
    Consensus CDS
    CCDS54442.1
    UniProtKB/Swiss-Prot
    A8K056, J3KNJ5, Q8WWR8, Q96D64
    UniProtKB/TrEMBL
    A8K211, B3KR54, Q3KR05
    Related
    ENSP00000385402.1, ENST00000407683.6
    Conserved Domains (1) summary
    cd15482
    Location:10 → 456
    Sialidase_non-viral; Non-viral sialidases

  3. NM_001167601.3 → NP_001161073.1  sialidase-4 isoform 3

    See identical proteins and their annotated locations for NP_001161073.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternate exon at the 5' end and uses an alternate acceptor splice site at the next exon compared to variant 1. This results in translation initiation from an in-frame downstream AUG, and an isoform (3, also known as NEU4 short) with a shorter N-terminus compared to isoform 1. Variants 3-5 encode the same isoform.
    Source sequence(s)
    AC131097, AY203952, BC063465, DC412650
    Consensus CDS
    CCDS54442.1
    UniProtKB/Swiss-Prot
    A8K056, J3KNJ5, Q8WWR8, Q96D64
    UniProtKB/TrEMBL
    A8K211, B3KR54, Q3KR05
    Related
    ENSP00000384804.1, ENST00000405370.5
    Conserved Domains (1) summary
    cd15482
    Location:10 → 456
    Sialidase_non-viral; Non-viral sialidases

  4. NM_001167602.3 → NP_001161074.1  sialidase-4 isoform 3

    See identical proteins and their annotated locations for NP_001161074.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) contains an additional exon at the 5' end compared to variant 1, resulting in translation initiation from an in-frame downstream AUG, and an isoform (3, also known as NEU4 short) with a shorter N-terminus compared to isoform 1. Variants 3-5 encode the same isoform.
    Source sequence(s)
    AC131097, AK091038, BC063465
    Consensus CDS
    CCDS54442.1
    UniProtKB/Swiss-Prot
    A8K056, J3KNJ5, Q8WWR8, Q96D64
    UniProtKB/TrEMBL
    A8K211, B3KR54, Q3KR05
    Related
    ENSP00000375830.2, ENST00000391969.6
    Conserved Domains (1) summary
    cd15482
    Location:10 → 456
    Sialidase_non-viral; Non-viral sialidases

  5. NM_080741.4 → NP_542779.2  sialidase-4 isoform 1

    See identical proteins and their annotated locations for NP_542779.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1 (also known as NEU4 long).
    Source sequence(s)
    AC131097, BC063465, BC117214
    Consensus CDS
    CCDS2553.1
    UniProtKB/TrEMBL
    A8K211, Q3KR05
    Related
    ENSP00000385149.1, ENST00000404257.5
    Conserved Domains (1) summary
    cd15482
    Location:22 → 468
    Sialidase_non-viral; Non-viral sialidases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    241809193..241817413
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NT_187527.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    21291..29511
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    242310986..242319206
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WWR8.3 GenPept UniProtKB/Swiss-Prot:Q8WWR8

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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