Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0NELQ1)

• DOT Name: Nucleoside diphosphate kinase A (NME1)
• Synonyms: NDK A; NDP kinase A; EC 2.7.4.6; Granzyme A-activated DNase; GAAD; Metastasis inhibition factor nm23; NM23-H1; Tumor metastatic process-associated protein
• Gene Name: NME1
• UniProt ID: NDKA_HUMAN
• PDB ID: 1JXV; 1UCN; 2HVD; 2HVE; 3L7U; 4ENO; 5UI4; 8OOV
• EC Number: 2.7.4.6
• Pfam ID: PF00334
• Sequence:
  MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVGLKFMQASEDLLKEHYVDLKDRPF
  FAGLVKYMHSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGS
  DSVESAEKEIGLWFHPEELVDYTSCAQNWIYE
• Function: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair.
• Tissue Specificity: Isoform 1 is expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen and thymus. Expressed in lung carcinoma cell lines but not in normal lung tissues. Isoform 2 is ubiquitously expressed and its expression is also related to tumor differentiation.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway:
  Azathioprine ADME (R-HSA-9748787)
  Ribavirin ADME (R-HSA-9755088)
  Interconversion of nucleotide di- and triphosphates (R-HSA-499943)
• BioCyc Pathway: MetaCyc:ENSG00000011052-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Nucleoside diphosphate kinase A (NME1) affects the response to substance of Fluorouracil.	[28]
Sulforaphane	DMQY3L0	Investigative	Nucleoside diphosphate kinase A (NME1) affects the binding of Sulforaphane.	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nucleoside diphosphate kinase A (NME1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleoside diphosphate kinase A (NME1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleoside diphosphate kinase A (NME1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleoside diphosphate kinase A (NME1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nucleoside diphosphate kinase A (NME1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nucleoside diphosphate kinase A (NME1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleoside diphosphate kinase A (NME1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nucleoside diphosphate kinase A (NME1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Nucleoside diphosphate kinase A (NME1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Nucleoside diphosphate kinase A (NME1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Nucleoside diphosphate kinase A (NME1).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Nucleoside diphosphate kinase A (NME1).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Nucleoside diphosphate kinase A (NME1).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Nucleoside diphosphate kinase A (NME1).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Nucleoside diphosphate kinase A (NME1).	[15]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Nucleoside diphosphate kinase A (NME1).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleoside diphosphate kinase A (NME1).	[17]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Nucleoside diphosphate kinase A (NME1).	[18]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of Nucleoside diphosphate kinase A (NME1).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleoside diphosphate kinase A (NME1).	[21]
Terfenadine	DM4KLPT	Withdrawn from market	Terfenadine increases the expression of Nucleoside diphosphate kinase A (NME1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleoside diphosphate kinase A (NME1).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nucleoside diphosphate kinase A (NME1).	[24]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Nucleoside diphosphate kinase A (NME1).	[25]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Nucleoside diphosphate kinase A (NME1).	[26]
Myricetin	DMTV4L0	Investigative	Myricetin increases the expression of Nucleoside diphosphate kinase A (NME1).	[27]

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 increases the methylation of Nucleoside diphosphate kinase A (NME1).	[20]

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