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    ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 [ Homo sapiens (human) ]

    Gene ID: 5168, updated on 11-Apr-2024

    Summary

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    Official Symbol
    ENPP2provided by HGNC
    Official Full Name
    ectonucleotide pyrophosphatase/phosphodiesterase 2provided by HGNC
    Primary source
    HGNC:HGNC:3357
    See related
    Ensembl:ENSG00000136960 MIM:601060; AllianceGenome:HGNC:3357
    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
    ATX; NPP2; ATX-X; PDNP2; LysoPLD; AUTOTAXIN; PD-IALPHA
    Summary
    The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2008]
    Expression
    Broad expression in placenta (RPKM 83.1), brain (RPKM 52.1) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    8q24.12
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (119557086..119673390, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (120685947..120802252, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (120569326..120685630, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene NANOG hESC enhancer GRCh37_chr8:120437890-120438632 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr8:120450916-120452115 Neighboring gene cellular communication network factor 3 Neighboring gene zinc finger protein 532 pseudogene Neighboring gene Sharpr-MPRA regulatory region 15323 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr8:120609160-120609857 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19482 Neighboring gene CYCS pseudogene 23 Neighboring gene Sharpr-MPRA regulatory region 2988 Neighboring gene uncharacterized LOC105375727 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:120684845-120685448 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:120685449-120686051 Neighboring gene RN7SK pseudogene 153 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27841 Neighboring gene TATA-box binding protein associated factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27842 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27843

    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. The Role of Autotaxin and LPA Signaling in Embryonic Development, Pathophysiology and Cancer. Magkrioti C, et al. Int J Mol Sci, 2023 May 5. PMID 37176032, Free PMC Article
    2. Role of Autotaxin in High Glucose-Induced Human ARPE-19 Cells. Liu Y, et al. Int J Mol Sci, 2022 Aug 16. PMID 36012446, Free PMC Article
    3. ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker. Panagopoulou M, et al. Int J Mol Sci, 2022 Mar 28. PMID 35409077, Free PMC Article
    4. Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8(+) T cells. Matas-Rico E, et al. Cell Rep, 2021 Nov 16. PMID 34788605, Free PMC Article
    5. ENPP2 Methylation in Health and Cancer. Panagopoulou M, et al. Int J Mol Sci, 2021 Nov 4. PMID 34769391, Free PMC Article

    See all (199) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Diagnostic value of serum autotaxin level in colorectal cancer.
      Title: Diagnostic value of serum autotaxin level in colorectal cancer.
    2. Dysregulation of the LPC-ATX-LPA axis in autoimmune hepatitis is associated with monocyte activation.
      Title: Dysregulation of the LPC-ATX-LPA axis in autoimmune hepatitis is associated with monocyte activation.
    3. Dual role of autotaxin as novel biomarker and therapeutic target in pancreatic neuroendocrine neoplasms.
      Title: Dual role of autotaxin as novel biomarker and therapeutic target in pancreatic neuroendocrine neoplasms.
    4. E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: Repression by p53 in murine but not in human carcinomas.
      Title: E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: Repression by p53 in murine but not in human carcinomas.
    5. The Role of Autotaxin and LPA Signaling in Embryonic Development, Pathophysiology and Cancer.
      Title: The Role of Autotaxin and LPA Signaling in Embryonic Development, Pathophysiology and Cancer.
    6. Hypoxia Increases ATX Expression by Histone Crotonylation in a HIF-2alpha-Dependent Manner.
      Title: Hypoxia Increases ATX Expression by Histone Crotonylation in a HIF-2α-Dependent Manner.
    7. Genotype-Phenotype Correlations for ATX-TBP (SCA17): MDSGene Systematic Review.
      Title: Genotype-Phenotype Correlations for ATX-TBP (SCA17): MDSGene Systematic Review.
    8. Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor.
      Title: Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor.
    9. Role of Autotaxin in High Glucose-Induced Human ARPE-19 Cells.
      Title: Role of Autotaxin in High Glucose-Induced Human ARPE-19 Cells.
    10. ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker.
      Title: ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker.
    Submit: New GeneRIF Correction See all GeneRIFs (170)

    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

    EBI GWAS Catalog

    Description
    Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
    EBI GWAS Catalog

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) in human B cells PubMed
    Tat tat HIV-1 Tat decreases Autotaxin (ENPP2) secretion by mouse brain oligodendrocytes PubMed
    tat HIV-1 Tat inhibits Autotaxin (ENPP2) lysophospholipase D (lysoPLD) function of converting to lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) in oligodendrocytes PubMed
    tat HIV-1 Tat interacts with Autotaxin (ENPP2) in mouse brain oligodendrocytes PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • FLJ26803

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables alkylglycerophosphoethanolamine phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables hydrolase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables lysophospholipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables lysophospholipase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables nucleic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphodiesterase I activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables polysaccharide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables scavenger receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables zinc ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell motility TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in chemotaxis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphatidylcholine catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in phosphatidylcholine catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in phospholipid catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of epithelial cell migration IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in positive regulation of epithelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of lamellipodium morphogenesis IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in positive regulation of peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sphingolipid catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vesicle-mediated transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular space ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ectonucleotide pyrophosphatase/phosphodiesterase family member 2
    Names
    E-NPP 2
    autotaxin-t
    extracellular lysophospholipase D
    phosphodiesterase I/nucleotide pyrophosphatase 2
    plasma lysophospholipase D
    NP_001035181.1
    NP_001124335.1
    NP_001317529.1
    NP_006200.3
    XP_006716647.1
    XP_006716648.1
    XP_006716650.1
    XP_016869061.1
    XP_016869062.1
    XP_016869063.1
    XP_016869064.1
    XP_024302949.1
    XP_024302950.1
    XP_054216623.1
    XP_054216624.1
    XP_054216625.1
    XP_054216626.1
    XP_054216627.1
    XP_054216628.1
    XP_054216629.1
    XP_054216630.1
    XP_054216631.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_029498.3 RefSeqGene

      Range
      39738..121491
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001040092.3 → NP_001035181.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform 2 preproprotein

      See identical proteins and their annotated locations for NP_001035181.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2, also known as beta) is shorter than isoform 1.
      Source sequence(s)
      AI375195, AK315253, DA922156
      Consensus CDS
      CCDS34936.1
      UniProtKB/Swiss-Prot
      A8UHA1, E9PHP7, Q13822, Q13827, Q14555, Q15117, Q9UCQ8, Q9UCR0, Q9UCR1, Q9UCR2, Q9UCR3, Q9UCR4
      Related
      ENSP00000075322.6, ENST00000075322.11
      Conserved Domains (3) summary
      smart00201
      Location:55 → 98
      SO; Somatomedin B -like domains
      smart00477
      Location:615 → 845
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:166 → 478
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase

    2. NM_001130863.3 → NP_001124335.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform 3 preproprotein

      See identical proteins and their annotated locations for NP_001124335.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks includes an alternate exon in the 5' coding region and lacks an exon in the 3' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3, also known as gamma) is shorter than isoform 1.
      Source sequence(s)
      AC099818, AI375195, CA390514, DB468753, EU131011
      Consensus CDS
      CCDS47914.1
      UniProtKB/Swiss-Prot
      Q13822
      Related
      ENSP00000428291.1, ENST00000522826.5
      Conserved Domains (4) summary
      smart00201
      Location:55 → 98
      SO; Somatomedin B -like domains
      smart00477
      Location:640 → 870
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:166 → 478
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase
      cd16018
      Location:164 → 518
      Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

    3. NM_001330600.2 → NP_001317529.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC099818, AC107960
      Consensus CDS
      CCDS83317.1
      UniProtKB/TrEMBL
      E7EUF1
      Related
      ENSP00000403315.2, ENST00000427067.6

    4. NM_006209.5 → NP_006200.3  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_006200.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1, also known as alpha).
      Source sequence(s)
      AA256687, AC099818, DB468753, L35594
      Consensus CDS
      CCDS6329.1
      UniProtKB/Swiss-Prot
      Q13822
      Related
      ENSP00000259486.6, ENST00000259486.10
      Conserved Domains (4) summary
      smart00201
      Location:55 → 98
      SO; Somatomedin B -like domains
      smart00477
      Location:667 → 897
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:166 → 530
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase
      cd16018
      Location:164 → 570
      Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

    RNA

    1. NR_045555.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate 5'-most exon compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA256687, AK130313, BM694754, DA919550, DA922156
      Related
      ENST00000522167.5

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      119557086..119673390 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024447182.2 → XP_024302950.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X9

      Conserved Domains (3) summary
      smart00201
      Location:51 → 94
      SO; Somatomedin B -like domains
      smart00477
      Location:607 → 837
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:162 → 474
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase

    2. XM_017013573.2 → XP_016869062.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X6

    3. XM_017013574.2 → XP_016869063.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X8

    4. XM_024447181.2 → XP_024302949.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X2

      Conserved Domains (3) summary
      smart00201
      Location:51 → 94
      SO; Somatomedin B -like domains
      smart00477
      Location:688 → 918
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:162 → 526
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase

    5. XM_017013575.2 → XP_016869064.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X7

    6. XM_017013572.2 → XP_016869061.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X5

    7. XM_006716587.2 → XP_006716650.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X4

      Conserved Domains (4) summary
      smart00201
      Location:55 → 98
      SO; Somatomedin B -like domains
      smart00477
      Location:663 → 893
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:166 → 530
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase
      cd16018
      Location:164 → 570
      Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

    8. XM_006716585.2 → XP_006716648.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X3

      Conserved Domains (4) summary
      smart00201
      Location:55 → 98
      SO; Somatomedin B -like domains
      smart00477
      Location:688 → 918
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:166 → 530
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase
      cd16018
      Location:164 → 570
      Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

    9. XM_006716584.2 → XP_006716647.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X1

      Conserved Domains (4) summary
      smart00201
      Location:55 → 98
      SO; Somatomedin B -like domains
      smart00477
      Location:692 → 922
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:166 → 530
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase
      cd16018
      Location:164 → 570
      Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      120685947..120802252 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360656.1 → XP_054216631.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X9

    2. XM_054360653.1 → XP_054216628.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X6

    3. XM_054360655.1 → XP_054216630.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X8

    4. XM_054360649.1 → XP_054216624.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X2

    5. XM_054360654.1 → XP_054216629.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X7

    6. XM_054360652.1 → XP_054216627.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X5

    7. XM_054360651.1 → XP_054216626.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X4

    8. XM_054360650.1 → XP_054216625.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X3

    9. XM_054360648.1 → XP_054216623.1  ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13822.3 GenPept UniProtKB/Swiss-Prot:Q13822

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