Details for: ENTPD2

Gene ID: 954

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ENTPD2

Ensembl ID: ENSG00000054179

Description: ectonucleoside triphosphate diphosphohydrolase 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • mature astrocyte CL0002627
    CSI 5.23
    rCSI 22.22%
    PRS 93.87
  • pancreatic PP cell CL0002275
    CSI 3.38
    rCSI 13.45%
    PRS 97.21
  • stem cell CL0000034
    CSI 2.83
    rCSI 2.73%
    PRS 96
  • colonocyte CL1000347
    CSI 2.53
    rCSI 3.63%
    PRS 96.23
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.43
    rCSI 5.46%
    PRS 92.06
  • basal cell of epidermis CL0002187
    CSI 2.17
    rCSI 3.85%
    PRS 77.45
  • melanocyte of skin CL1000458
    CSI 1.75
    rCSI 2.39%
    PRS 78.45
  • mesenchymal cell CL0008019
    CSI 1.41
    rCSI 3.58%
    PRS 95.84
  • helper T cell CL0000912
    CSI 1.17
    rCSI 1.65%
    PRS 92.88
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.07
    rCSI 1.3%
    PRS 83.49

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ENTPD2](/details-gene/954) (Ectonucleoside Triphosphate Diphosphohydrolase 2) is a protein-coding gene located on chromosome 9q34.3 that encodes a cell surface enzyme critical for nucleotide metabolism. As a member of the E-NTPDase family, it hydrolyzes extracellular nucleoside triphosphates and diphosphates, such as ATP and ADP, to their monophosphate forms [Link](https://doi.org/10.1038/sj.bjp.0702805). This function places [ENTPD2](/details-gene/954) as a key regulator of purinergic signaling, a ubiquitous pathway involved in processes ranging from neurotransmission to immune regulation and platelet activation. Expression data indicates its significance is highest in [mature astrocyte](/details-cell/CL0002627), [pancreatic PP cell](/details-cell/CL0002275), and [stem cell](/details-cell/CL0000034), highlighting its diverse roles in the central nervous system, endocrine regulation, and tissue homeostasis. Its clinical relevance is noted under OMIM entry [602012](https://omim.org/entry/602012). ## Cellular Roles and Expression Landscape The expression profile of [ENTPD2](/details-gene/954) suggests a broad but specific role in regulating the extracellular nucleotide environment across diverse cell types rather than serving as a simple lineage marker. **Overall**, its most significant expression is observed in [mature astrocyte](/details-cell/CL0002627) and [astrocyte of the cerebral cortex](/details-cell/CL0002605), pointing to a primary function in the central nervous system, likely modulating neuro-glial communication and synaptic plasticity by controlling ATP and ADP concentrations. Beyond the nervous system, [ENTPD2](/details-gene/954) shows high significance in specialized secretory and progenitor cells. Its prominence in [pancreatic PP cell](/details-cell/CL0002275) suggests a role in endocrine signaling and metabolic regulation within the pancreas. Furthermore, its notable expression in [stem cell](/details-cell/CL0000034), [basal cell of epidermis](/details-cell/CL0002187), and [mesenchymal cell](/details-cell/CL0008019) is consistent with a function in maintaining progenitor cell niches and orchestrating tissue development or repair. A moderate but significant expression is also seen in adaptive immune cells, including [helper T cell](/details-cell/CL0000912) and memory T cells, where it may contribute to fine-tuning immune responses by catabolizing pro-inflammatory extracellular ATP. The wide distribution across functionally distinct cell types underscores its fundamental role in controlling purinergic signaling pathways. ## Pathways and Molecular Function The molecular functions attributed to [ENTPD2](/details-gene/954) are centered on its enzymatic activity as a nucleotide hydrolase. Gene Ontology annotations confirm its role in [nucleoside diphosphate catabolic process](/details-go/GO:0009134) and specifically highlight its [GDP phosphatase activity](/details-go/GO:0004382), [UDP phosphatase activity](/details-go/GO:0045134), and [ribonucleoside triphosphate phosphatase activity](/details-go/GO:0017111). Consistent with this, Reactome pathways place it centrally within [Metabolism of nucleotides](/details-reactome/R-HSA-15869) and, more specifically, [Phosphate bond hydrolysis by NTPDase proteins](/details-reactome/R-HSA-8850843). These enzymatic functions are directly linked to broader biological processes. By hydrolyzing ATP and ADP, [ENTPD2](/details-gene/954) influences [G protein-coupled receptor signaling pathway](/details-go/GO:0007186), as many purinergic receptors are GPCRs. Its involvement in [platelet activation](/details-go/GO:0030168) is consistent with the critical role of ADP in promoting platelet aggregation. This molecular activity, executed at the [plasma membrane](/details-go/GO:0005886) and within the [endoplasmic reticulum membrane](/details-go/GO:0005789), allows cells to precisely control local signaling cues, a function that aligns with its high expression in neurologically and metabolically active cell types like astrocytes and pancreatic cells. ## Research Directions The diverse expression pattern of [ENTPD2](/details-gene/954) across neural, endocrine, and progenitor cells suggests it acts as a critical homeostatic regulator whose dysregulation could contribute to various pathologies. **Proposed Hypotheses:** 1. Given its premier expression in [mature astrocyte](/details-cell/CL0002627) and its function in hydrolyzing pro-inflammatory extracellular ATP, [ENTPD2](/details-gene/954) is a key suppressor of neuroinflammation. Its downregulation or loss-of-function during neurological injury or disease may lead to an exacerbated inflammatory response and subsequent neuronal damage. 2. The high significance of [ENTPD2](/details-gene/954) in [stem cell](/details-cell/CL0000034) and [basal cell of epidermis](/details-cell/CL0002187) suggests it maintains the quiescence and regenerative potential of progenitor niches by keeping extracellular ATP levels low. Elevated ATP in these niches could act as a signal that triggers premature differentiation or cellular stress, and [ENTPD2](/details-gene/954) may act as a gatekeeper against such signals. **Key Experimental Approach:** To test the first hypothesis regarding neuroinflammation, a compelling experiment would involve a targeted knockout of [ENTPD2](/details-gene/954) in astrocytes. One could utilize CRISPR-Cas9 to generate an astrocyte-specific conditional knockout mouse model (e.g., using a GFAP-Cre driver). These mice, alongside wild-type controls, could be subjected to a neuroinflammatory challenge, such as lipopolysaccharide (LPS) injection or an experimental autoimmune encephalomyelitis (EAE) model. Subsequent analysis would involve quantifying inflammatory cytokine expression (TNF-alpha, IL-1beta) in brain tissue via qPCR and ELISA, measuring immune cell infiltration through immunohistochemistry, and assessing neuronal health. This approach would directly test whether the absence of astrocytic [ENTPD2](/details-gene/954) potentiates the inflammatory cascade and worsens pathological outcomes *in vivo*. **Therapeutic Potential:** As a cell-surface ecto-enzyme, [ENTPD2](/details-gene/954) is an accessible therapeutic target. Its function in degrading pro-inflammatory and pro-thrombotic nucleotides suggests that its **activation** could be a viable strategy for diseases characterized by excessive purinergic signaling, such as chronic inflammation, certain cancers, or thrombotic disorders. Development of small molecule activators or protein-based therapeutics could help dampen these pathological signals. Conversely, in the context of cancer immunotherapy where extracellular ATP can act as an adjuvant to stimulate anti-tumor immunity, targeted **inhibition** of [ENTPD2](/details-gene/954) within the tumor microenvironment might enhance therapeutic efficacy. However, its broad expression profile necessitates a highly targeted approach to minimize potential systemic side effects.

Genular Protein ID: 2671766504

Symbol: ENTP2_HUMAN

Name: Ectonucleoside triphosphate diphosphohydrolase 2

UniProtKB Accession Codes:

Q9Y5L3 O15464 Q5SPY6 Q5SPY7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CPTAC 1 CTD 1 ChEBI 3 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 7 Ensembl 2 GO 12 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 2 SABIO-RK 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9271669

Title: Cloning and mapping of a human and mouse gene with homology to ecto-ATPase genes.

PubMed ID: 9271669

DOI: 10.1007/s003359900534

PubMed ID: 10510450

Title: Functional expression of a cDNA encoding a human ecto-ATPase.

PubMed ID: 10510450

DOI: 10.1038/sj.bjp.0702805

PubMed ID: 16101300

Title: 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).

PubMed ID: 16101300

DOI: 10.1021/bi050019k

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 12888562

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.

PubMed ID: 12888562

DOI: 10.1074/jbc.m307854200

Sequence Information:

  • Length: 495
  • Mass: 53665
  • Checksum: 3BDBA114A679B422
  • Sequence:
    • MAGKVRSLLP PLLLAAAGLA GLLLLCVPTR DVREPPALKY GIVLDAGSSH TSMFIYKWPA 
DKENDTGIVG QHSSCDVPGG GISSYADNPS GASQSLVGCL EQALQDVPKE RHAGTPLYLG 
ATAGMRLLNL TNPEASTSVL MAVTHTLTQY PFDFRGARIL SGQEEGVFGW VTANYLLENF 
IKYGWVGRWF RPRKGTLGAM DLGGASTQIT FETTSPAEDR ASEVQLHLYG QHYRVYTHSF 
LCYGRDQVLQ RLLASALQTH GFHPCWPRGF STQVLLGDVY QSPCTMAQRP QNFNSSARVS 
LSGSSDPHLC RDLVSGLFSF SSCPFSRCSF NGVFQPPVAG NFVAFSAFFY TVDFLRTSMG 
LPVATLQQLE AAAVNVCNQT WAQLQARVPG QRARLADYCA GAMFVQQLLS RGYGFDERAF 
GGVIFQKKAA DTAVGWALGY MLNLTNLIPA DPPGLRKGTD FSSWVVLLLL FASALLAALV 
LLLRQVHSAK LPSTI