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    ENTPD2 ectonucleoside triphosphate diphosphohydrolase 2 [ Homo sapiens (human) ]

    Gene ID: 954, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ENTPD2provided by HGNC
    Official Full Name
    ectonucleoside triphosphate diphosphohydrolase 2provided by HGNC
    Primary source
    HGNC:HGNC:3364
    See related
    Ensembl:ENSG00000054179 MIM:602012; AllianceGenome:HGNC:3364
    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
    Also known as
    CD39L1; NTPDase-2
    Summary
    The protein encoded by this gene is the type 2 enzyme of the ecto-nucleoside triphosphate diphosphohydrolase family (E-NTPDase). E-NTPDases are a family of ecto-nucleosidases that hydrolyze 5'-triphosphates. This ecto-ATPase is an integral membrane protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in duodenum (RPKM 4.7), prostate (RPKM 4.6) and 17 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ENTPD2 in Genome Data Viewer
    Location:
    9q34.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (137048107..137054061, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (149283232..149291667, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (139942559..139948513, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29338 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:139929142-139930030 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:139930031-139930917 Neighboring gene fucosyltransferase 7 Neighboring gene neural proliferation, differentiation and control 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:139940694-139941363 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139943096-139943624 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139943625-139944153 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20567 Neighboring gene uncharacterized LOC105376327 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20568 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20569 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139958261-139959038 Neighboring gene suppressor APC domain containing 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139962228-139963208 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20571 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20572 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20573 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139965171-139966150 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139968734-139969347 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20574 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20575 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20576 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20577 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139972693-139973571 Neighboring gene UDP-N-acetylglucosamine pyrophosphorylase 1 like 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:139977971-139978205

    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 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. Transmembrane domains confer different substrate specificities and adenosine diphosphate hydrolysis mechanisms on CD39, CD39L1, and chimeras. Grinthal A, et al. Biochemistry, 2002 Feb 12. PMID 11827541
    2. Requirement of Cys399 for processing of the human ecto-ATPase (NTPDase2) and its implications for determination of the activities of splice variants of the enzyme. Mateo J, et al. J Biol Chem, 2003 Oct 10. PMID 12888562
    3. Enzymatic and transcriptional regulation of human ecto-ATPase/E-NTPDase 2. Knowles AF, et al. Arch Biochem Biophys, 2003 Oct 15. PMID 14522593
    4. Either the carboxyl- or the amino-terminal region of the human ecto-ATPase (E-NTPDase 2) confers detergent and temperature sensitivity to the chicken ecto-ATP-diphosphohydrolase (E-NTPDase 8). Mukasa T, et al. Biochemistry, 2005 Aug 23. PMID 16101300
    5. Inhibition of human NTPDase 2 by modification of an intramembrane cysteine by p-chloromercuriphenylsulfonate and oxidative cross-linking of the transmembrane domains. Chiang WC, et al. Biochemistry, 2008 Aug 19. PMID 18656957

    See all (26) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. In oviducts, remarkably, ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), with the ability to hydrolyze ATP to AMP, are expressed in ciliated epithelial cells but with different subcellular localization.
      Title: Characterization of ecto-nucleotidases in human oviducts with an improved approach simultaneously identifying protein expression and in situ enzyme activity.
    2. Hypoxia upregulates ENTPD2 through HIF-1alpha in hepatocellular carcinoma and subsequently leading to the accumulation of extracellular 5'-AMP, which maintains myeloid-derived suppressor cells undifferentiated.
      Title: Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma.
    3. NTPDase2 and -3 are ecto-enzymes expressed in the enteric nervous system. Both enzymes confer protection against gut inflammation in experimental colitis and exhibit alterations in Crohn's disease. These observations suggest that purinergic signalling modulated by E-NTPDases governs neuro-immune interactions that are relevant in Crohn's disease.
      Title: Expression of Ecto-nucleoside Triphosphate Diphosphohydrolases-2 and -3 in the Enteric Nervous System Affects Inflammation in Experimental Colitis and Crohn's Disease.
    4. The role of cysteine 26 in the catalytic activity of NTPDase-2 and as the target of p-chloromercuriphenylsulfonate (pCMPS), a sulfhydryl reagent and NTPDase-2 inhibitor, is reported.
      Title: Inhibition of human NTPDase 2 by modification of an intramembrane cysteine by p-chloromercuriphenylsulfonate and oxidative cross-linking of the transmembrane domains.
    5. the lack of ecto-nucleotidase activity exhibited by NTPDase2 beta and -2 gamma and the C399S mutant, as well as the large reduction of activity in the N443D mutant are due to alterations in the folding/maturation of these proteins
      Title: Requirement of Cys399 for processing of the human ecto-ATPase (NTPDase2) and its implications for determination of the activities of splice variants of the enzyme.
    6. down-regulation in biliary cirrhosis
      Title: Ectonucleotidase NTPDase2 is selectively down-regulated in biliary cirrhosis.
    7. NTPDase2 preferentially hydrolyzes nucleoside triphosphates.
      Title: Regulation of P2Y1 receptor-mediated signaling by the ectonucleoside triphosphate diphosphohydrolase isozymes NTPDase1 and NTPDase2.
    8. Mutagenesis study indicate the importance of K62 located in CR1, K182 downstream of ACR3, and R155. Mutation of Asp at the six potential glycosylation sites showed the importance of N64 in CR1 and N443 in ACR5 in protein function and expression
      Title: Mutagenesis of lysine 62, asparagine 64, and conserved region 1 reduces the activity of human ecto-ATPase (NTPDase 2).
    9. NTPDase2 has a role in portal fibroblast regulation of bile duct epithelium proliferation
      Title: Portal fibroblasts regulate the proliferation of bile duct epithelia via expression of NTPDase2.
    Submit: New GeneRIF Correction

    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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    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables GDP phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables UDP phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ribonucleoside triphosphate phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nucleoside diphosphate catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in platelet activation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in purine ribonucleoside diphosphate catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in basement membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    ectonucleoside triphosphate diphosphohydrolase 2
    Names
    CD39 antigen-like 1
    NTPDase 2
    ecto-ATP diphosphohydrolase 2
    ecto-ATPDase 2
    ecto-ATPase 2
    NP_001237.1
    NP_982293.1
    XP_011517514.1
    XP_054220181.1
    XP_054220182.1
    XP_054220183.1
    XP_054220184.1

    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.

    Genomic

    1. NG_029427.1 RefSeqGene

      Range
      4993..10947
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001246.4 → NP_001237.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform 2

      See identical proteins and their annotated locations for NP_001237.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AF144748, AL807752, BC035738, CB045339, U91510
      Consensus CDS
      CCDS7025.1
      UniProtKB/Swiss-Prot
      Q9Y5L3
      Related
      ENSP00000312494.5, ENST00000312665.7
      Conserved Domains (1) summary
      cl17037
      Location:39 → 430
      NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

    2. NM_203468.3 → NP_982293.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform 1

      See identical proteins and their annotated locations for NP_982293.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AF144748, AL807752, BC035738, CB045339
      Consensus CDS
      CCDS7026.1
      UniProtKB/Swiss-Prot
      O15464, Q5SPY6, Q5SPY7, Q9Y5L3
      Related
      ENSP00000347213.2, ENST00000355097.7
      Conserved Domains (1) summary
      cl17037
      Location:39 → 453
      NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      137048107..137054061 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011519212.3 → XP_011517514.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform X1

      Conserved Domains (1) summary
      cl17037
      Location:31 → 350
      NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      149283232..149291667 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054364206.1 → XP_054220181.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform X2

    2. XM_054364207.1 → XP_054220182.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform X2

    3. XM_054364208.1 → XP_054220183.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform X3

    4. XM_054364209.1 → XP_054220184.1  ectonucleoside triphosphate diphosphohydrolase 2 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y5L3.1 GenPept UniProtKB/Swiss-Prot:Q9Y5L3

    Gene LinkOut

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

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