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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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See ENPP2 in Genome Data Viewer
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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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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