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

Summary

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

Location:: 8q24.12

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (119557086..119673390, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (120685947..120802252, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (120569326..120685630, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Lysophospholipase D activity on oral mucosa cells in whole mixed human saliva involves in production of bioactive lysophosphatidic acid from lysophosphatidylcholine.
Title: Lysophospholipase D activity on oral mucosa cells in whole mixed human saliva involves in production of bioactive lysophosphatidic acid from lysophosphatidylcholine.
LPA and Autotaxin: Potential Drug Targets in Asthma?
Title: LPA and Autotaxin: Potential Drug Targets in Asthma?
Diagnostic value of serum autotaxin level in colorectal cancer.
Title: Diagnostic value of serum autotaxin level in colorectal cancer.
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.
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.
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.
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.
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.
Genotype-Phenotype Correlations for ATX-TBP (SCA17): MDSGene Systematic Review.
Title: Genotype-Phenotype Correlations for ATX-TBP (SCA17): MDSGene Systematic Review.
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.

Submit: New GeneRIF Correction See all GeneRIFs (172)

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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-12938 (e-PCR)
- UniSTS:68354

SHGC-142128 (e-PCR)
- UniSTS:171273

D8S269 (e-PCR), detects polymorphism
- UniSTS:30229

SHGC-112215 (e-PCR)
- UniSTS:168523

RH69056 (e-PCR)
- UniSTS:34401

G32527 (e-PCR)
- UniSTS:117112

WI-21702 (e-PCR)
- UniSTS:45964

SHGC-111401 (e-PCR)
- UniSTS:168349

D8S1677E (e-PCR)
- UniSTS:154044

RH41114 (e-PCR)
- UniSTS:85190

A009G17 (e-PCR)
- UniSTS:28617

STS-R51085 (e-PCR)
- UniSTS:70908

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 phospholipase D activity	IEA Inferred from Electronic Annotation 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: autotaxin

Names: E-NPP 2; autotaxin-t; ectonucleotide pyrophosphatase/phosphodiesterase family member 2; extracellular lysophospholipase D; phosphodiesterase I/nucleotide pyrophosphatase 2; plasma lysophospholipase D

NP_001035181.1

EC 3.1.4.39

EC 3.1.4.4

NP_001124335.1

EC 3.1.4.39

EC 3.1.4.4

NP_001317529.1

EC 3.1.4.39

EC 3.1.4.4

NP_006200.3

EC 3.1.4.39

EC 3.1.4.4

XP_006716647.1

EC 3.1.4.39

EC 3.1.4.4

XP_006716648.1

EC 3.1.4.39

EC 3.1.4.4

XP_006716650.1

EC 3.1.4.39

EC 3.1.4.4

XP_016869061.1

EC 3.1.4.39

EC 3.1.4.4

XP_016869062.1

EC 3.1.4.39

EC 3.1.4.4

XP_016869063.1

EC 3.1.4.39

EC 3.1.4.4

XP_016869064.1

EC 3.1.4.39

EC 3.1.4.4

XP_024302949.1

EC 3.1.4.39

EC 3.1.4.4

XP_024302950.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216623.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216624.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216625.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216626.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216627.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216628.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216629.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216630.1

EC 3.1.4.39

EC 3.1.4.4

XP_054216631.1

EC 3.1.4.39

EC 3.1.4.4

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

NG_029498.3 RefSeqGene

Range

39738..121491

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001040092.3 → NP_001035181.1 autotaxin 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
NM_001130863.3 → NP_001124335.1 autotaxin 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
NM_001330600.2 → NP_001317529.1 autotaxin isoform 4

Status: REVIEWED

Source sequence(s)

AC099818, AC107960

Consensus CDS

CCDS83317.1

UniProtKB/TrEMBL

E7EUF1

Related

ENSP00000403315.2, ENST00000427067.6
NM_006209.5 → NP_006200.3 autotaxin 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

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

119557086..119673390 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024447182.2 → XP_024302950.1 autotaxin 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
XM_017013573.2 → XP_016869062.1 autotaxin isoform X6
XM_017013574.2 → XP_016869063.1 autotaxin isoform X8
XM_024447181.2 → XP_024302949.1 autotaxin 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
XM_017013575.2 → XP_016869064.1 autotaxin isoform X7
XM_017013572.2 → XP_016869061.1 autotaxin isoform X5
XM_006716587.2 → XP_006716650.1 autotaxin 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
XM_006716585.2 → XP_006716648.1 autotaxin 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
XM_006716584.2 → XP_006716647.1 autotaxin 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