ENPP3 ectonucleotide pyrophosphatase/phosphodiesterase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ENPP3provided by HGNC
Official Full Name: ectonucleotide pyrophosphatase/phosphodiesterase 3provided by HGNC
Primary source: HGNC:HGNC:3358
See related: Ensembl:ENSG00000154269 MIM:602182; AllianceGenome:HGNC:3358
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: B10; NPP3; PDNP3; CD203c; PD-IBETA
Summary: The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]
Expression: Biased expression in small intestine (RPKM 19.6), duodenum (RPKM 6.7) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q23.2

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (131637302..131747410)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (132822841..132942332)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (131958442..132068550)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway.
Title: Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway.
Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph[+] Chronic Myeloid Leukemia.
Title: Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia.
Activated steady status and distinctive FcepsilonRI-mediated responsiveness in basophils of atopic dermatitis.
Title: Activated steady status and distinctive FcεRI-mediated responsiveness in basophils of atopic dermatitis.
Serum CD203c+ Extracellular Vesicle Serves as a Novel Diagnostic and Prognostic Biomarker for Succinylated Gelatin Induced Perioperative Hypersensitive Reaction.
Title: Serum CD203c+ Extracellular Vesicle Serves as a Novel Diagnostic and Prognostic Biomarker for Succinylated Gelatin Induced Perioperative Hypersensitive Reaction.
Updates on the surface antigens of basophils: CD16 on basophils of patients with respiratory or insect venom allergy and the rejection of CD203c and CD63 externalization decoupling by bisindolylmaleimides.
Title: Updates on the surface antigens of basophils: CD16 on basophils of patients with respiratory or insect venom allergy and the rejection of CD203c and CD63 externalization decoupling by bisindolylmaleimides.
ENPP3 was detected at high levels in archived tumor samples in agreement with preclinical data
Title: Phase I Trials of Anti-ENPP3 Antibody-Drug Conjugates in Advanced Refractory Renal Cell Carcinomas.
ENPP3 was expressed in endometrial epithelial cells and its expression levels changed during the menstrual cycle, peaking in the mid-secretory phase, corresponding to the time of embryo implantation. ENPP3 may play an important role in embryo implantation and may be a unique biomarker of endometrial receptivity.
Title: Expression of ENPP3 in human cyclic endometrium: a novel molecule involved in embryo implantation.
Studies determined the crystal structure of ectonucleotide pyrophosphatase/phosphodiesterase 3 (NPP3) as well as its complex with an ATP analog.
Title: Structural basis for nucleotide recognition by the ectoenzyme CD203c.
We showed the ability of the immunological marker CD203c to predict the clinical efficacy of sublingual immunotherapy on rhinitis subjects allergic to Parietaria.
Title: Basophil biomarkers as useful predictors for sublingual immunotherapy in allergic rhinitis.
Basophil CD203c surface expression reliably discriminated cystic fibrosis with allergic bronchopulmonary aspergillosis from cystic fibrosis with Aspergillus colonization and cystic fibrosis over time.
Title: Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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
Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine. EBI GWAS Catalog EBI GWAS CatalogPubMed
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 8-oxo-(d)RTP hydrolase activity	IEA Inferred from Electronic Annotation more info
enables ATP diphosphatase activity	IEA Inferred from Electronic Annotation more info
enables GTP diphosphatase activity	IEA Inferred from Electronic Annotation more info
enables UTP diphosphatase activity	IEA Inferred from Electronic Annotation more info
enables bis(5'-adenosyl)-pentaphosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables bis(5'-adenosyl)-triphosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables nucleic acid binding	IEA Inferred from Electronic Annotation more info
enables nucleoside triphosphate diphosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nucleoside triphosphate diphosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphodiesterase I activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ATP metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in basophil activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
NOT involved_in inorganic diphosphate transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of mast cell activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of mast cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in nucleoside triphosphate catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in nucleoside triphosphate catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphate ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in phosphate-containing compound metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in pyrimidine nucleotide metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: ectonucleotide pyrophosphatase/phosphodiesterase family member 3

Names: NPPase; alkaline phosphodiesterase I; dJ1005H11.3 (phosphodiesterase I/nucleotide pyrophosphatase 3); dJ914N13.3 (phosphodiesterase I/nucleotide pyrophosphatase 3); dinucleoside polyphosphatase; gp130RB13-6; nucleotide diphosphatase; nucleotide pyrophosphatase; phosphodiesterase I/nucleotide pyrophosphatase 3; phosphodiesterase-I beta

NP_005012.2

EC 3.1.4.1

EC 3.6.1.9

XP_011534199.1

EC 3.1.4.1

EC 3.6.1.9

XP_016866421.1

EC 3.1.4.1

EC 3.6.1.9

XP_054211567.1

EC 3.1.4.1

EC 3.6.1.9

XP_054211568.1

EC 3.1.4.1

EC 3.6.1.9

XP_054211569.1

EC 3.1.4.1

EC 3.6.1.9

XP_054211570.1

EC 3.1.4.1

EC 3.6.1.9

XP_054211571.1

EC 3.1.4.1

EC 3.6.1.9

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_033982.1 RefSeqGene

Range

5001..115109

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005021.5 → NP_005012.2 ectonucleotide pyrophosphatase/phosphodiesterase family member 3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer, protein-coding transcript.

Source sequence(s)

AK024899, AL121575, EF560735, HY106781

Consensus CDS

CCDS5148.1

UniProtKB/Swiss-Prot

O14638, Q5JTL3

UniProtKB/TrEMBL

A8KA38

Related

ENSP00000350265.3, ENST00000357639.8

Conserved Domains (3) summary

smart00201
Location:94 → 137

SO; Somatomedin B -like domains

smart00477
Location:627 → 857

NUC; DNA/RNA non-specific endonuclease

cd16018
Location:159 → 525

Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

RNA

NR_133007.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate 3' exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK024899, AL121575, EF560735, HY106781

Related

ENST00000358229.6

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_000006.12 Reference GRCh38.p14 Primary Assembly

Range

131637302..131747410

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017010932.2 → XP_016866421.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X1

UniProtKB/TrEMBL

A8KA38
XM_011535897.2 → XP_011534199.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X2

Conserved Domains (3) summary

smart00477
Location:373 → 603

NUC; DNA/RNA non-specific endonuclease

pfam01663
Location:2 → 232

Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase

cd16018
Location:2 → 271

Enpp; Ectonucleotide pyrophosphatase/phosphodiesterase, also called autotaxin

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

132822841..132942332

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355593.1 → XP_054211568.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X3

UniProtKB/Swiss-Prot

O14638, Q5JTL3
XM_054355592.1 → XP_054211567.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X3

UniProtKB/Swiss-Prot

O14638, Q5JTL3
XM_054355595.1 → XP_054211570.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X4

UniProtKB/TrEMBL

F8W6H5
XM_054355594.1 → XP_054211569.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X1
XM_054355596.1 → XP_054211571.1 ectonucleotide pyrophosphatase/phosphodiesterase family member 3 isoform X2