Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFS4J1W)

• DOT Name: Asparagine--tRNA ligase, cytoplasmic (NARS1)
• Synonyms: EC 6.1.1.22; Asparaginyl-tRNA synthetase; AsnRS; Asparaginyl-tRNA synthetase 1
• Gene Name: NARS1
• Related Disease:
  Oral mucositis
  Abscess
  Analgesia
  Colorectal carcinoma
  Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities
  Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities
  Neoplasm
  Post-traumatic stress disorder
  Rectal carcinoma
• UniProt ID: SYNC_HUMAN
• PDB ID: 4ZYA; 5XIX; 8H53
• EC Number: 6.1.1.22
• Pfam ID: PF20917 ; PF00152 ; PF01336
• Sequence:
  MVLAELYVSDREGSDATGDGTKEKPFKTGLKALMTVGKEPFPTIYVDSQKENERWNVISK
  SQLKNIKKMWHREQMKSESREKKEAEDSLRREKNLEEAKKITIKNDPSLPEPKCVKIGAL
  EGYRGQRVKVFGWVHRLRRQGKNLMFLVLRDGTGYLQCVLADELCQCYNGVLLSTESSVA
  VYGMLNLTPKGKQAPGGHELSCDFWELIGLAPAGGADNLINEESDVDVQLNNRHMMIRGE
  NMSKILKARSMVTRCFRDHFFDRGYYEVTPPTLVQTQVEGGATLFKLDYFGEEAFLTQSS
  QLYLETCLPALGDVFCIAQSYRAEQSRTRRHLAEYTHVEAECPFLTFDDLLNRLEDLVCD
  VVDRILKSPAGSIVHELNPNFQPPKRPFKRMNYSDAIVWLKEHDVKKEDGTFYEFGEDIP
  EAPERLMTDTINEPILLCRFPVEIKSFYMQRCPEDSRLTESVDVLMPNVGEIVGGSMRIF
  DSEEILAGYKREGIDPTPYYWYTDQRKYGTCPHGGYGLGLERFLTWILNRYHIRDVCLYP
  RFVQRCTP
• Function: Catalyzes the attachment of asparagine to tRNA(Asn) in a two-step reaction: asparagine is first activated by ATP to form Asn-AMP and then transferred to the acceptor end of tRNA(Asn). In addition to its essential role in protein synthesis, acts as a signaling molecule that induced migration of CCR3-expressing cells. Has an essential role in the development of the cerebral cortex, being required for proper proliferation of radial glial cells.
• KEGG Pathway: Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway: Cytosolic tRNA aminoacylation (R-HSA-379716)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral mucositis	DISS93V5	Definitive	Biomarker	[1]
Abscess	DISAP982	Strong	Biomarker	[2]
Analgesia	DISK3TVI	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities	DISKI679	Strong	Autosomal recessive	[5]
Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities	DIS85QSG	Strong	Autosomal dominant	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[7]
Rectal carcinoma	DIS8FRR7	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[17]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[13]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[12]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[12]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[18]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[22]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[23]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the acetylation of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Asparagine--tRNA ligase, cytoplasmic (NARS1).	[19]

References

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• [2] Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial.J Am Acad Dermatol. 2019 Jan;80(1):80-88. doi: 10.1016/j.jaad.2018.06.046. Epub 2018 Jul 3.
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• [21] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [22] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
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• [24] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.