Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDA431Y)

• DOT Name: Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3)
• Synonyms: NTPDase 3; EC 3.6.1.5; CD39 antigen-like 3; Ecto-ATP diphosphohydrolase 3; Ecto-ATPDase 3; Ecto-ATPase 3; Ecto-apyrase 3; HB6
• Gene Name: ENTPD3
• UniProt ID: ENTP3_HUMAN
• EC Number: 3.6.1.5
• Pfam ID: PF01150
• Sequence:
  MFTVLTRQPCEQAGLKALYRTPTIIALVVLLVSIVVLVSITVIQIHKQEVLPPGLKYGIV
  LDAGSSRTTVYVYQWPAEKENNTGVVSQTFKCSVKGSGISSYGNNPQDVPRAFEECMQKV
  KGQVPSHLHGSTPIHLGATAGMRLLRLQNETAANEVLESIQSYFKSQPFDFRGAQIISGQ
  EEGVYGWITANYLMGNFLEKNLWHMWVHPHGVETTGALDLGGASTQISFVAGEKMDLNTS
  DIMQVSLYGYVYTLYTHSFQCYGRNEAEKKFLAMLLQNSPTKNHLTNPCYPRDYSISFTM
  GHVFDSLCTVDQRPESYNPNDVITFEGTGDPSLCKEKVASIFDFKACHDQETCSFDGVYQ
  PKIKGPFVAFAGFYYTASALNLSGSFSLDTFNSSTWNFCSQNWSQLPLLLPKFDEVYARS
  YCFSANYIYHLFVNGYKFTEETWPQIHFEKEVGNSSIAWSLGYMLSLTNQIPAESPLIRL
  PIEPPVFVGTLAFFTAAALLCLAFLAYLCSATRRKRHSEHAFDHAVDSD
• Function: Has a threefold preference for the hydrolysis of ATP over ADP.
• Tissue Specificity: Expressed in adult brain, pancreas, spleen and prostate . Moderate or low expression is seen in most tissues . Not expressed in liver and peripheral blood leukocytes .
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway: Phosphate bond hydrolysis by NTPDase proteins (R-HSA-8850843)

Molecular Interaction Atlas (MIA) of This DOT

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3).	[1]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3).	[3]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3).	[3]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3).	[4]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3).	[5]

References

• [1] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [4] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.