Details of Drug Off-Target (DOT)

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

• DOT Name: Tryptophan--tRNA ligase, cytoplasmic
• Synonyms: EC 6.1.1.2; Interferon-induced protein 53; IFP53; Tryptophanyl-tRNA synthetase; TrpRS; hWRS
• Gene Name: WARS1
• Related Disease:
  Neuronopathy, distal hereditary motor, type 9
  Distal hereditary motor neuropathy
• UniProt ID: SYWC_HUMAN
• PDB ID: 1O5T; 1R6T; 1R6U; 1ULH; 2AKE; 2AZX; 2DR2; 2QUH; 2QUI; 2QUJ; 2QUK; 5UJI; 5UJJ
• EC Number: 6.1.1.2
• Pfam ID: PF00579 ; PF00458
• Sequence:
  MPNSEPASLLELFNSIATQGELVRSLKAGNASKDEIDSAVKMLVSLKMSYKAAAGEDYKA
  DCPPGNPAPTSNHGPDATEAEEDFVDPWTVQTSSAKGIDYDKLIVRFGSSKIDKELINRI
  ERATGQRPHHFLRRGIFFSHRDMNQVLDAYENKKPFYLYTGRGPSSEAMHVGHLIPFIFT
  KWLQDVFNVPLVIQMTDDEKYLWKDLTLDQAYSYAVENAKDIIACGFDINKTFIFSDLDY
  MGMSSGFYKNVVKIQKHVTFNQVKGIFGFTDSDCIGKISFPAIQAAPSFSNSFPQIFRDR
  TDIQCLIPCAIDQDPYFRMTRDVAPRIGYPKPALLHSTFFPALQGAQTKMSASDPNSSIF
  LTDTAKQIKTKVNKHAFSGGRDTIEEHRQFGGNCDVDVSFMYLTFFLEDDDKLEQIRKDY
  TSGAMLTGELKKALIEVLQPLIAEHQARRKEVTDEIVKEFMTPRKLSFDFQ
• Function: Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp); [Isoform 1]: Has no angiostatic activity; [T2-TrpRS]: Possesses an angiostatic activity but has no aminoacylation activity. Inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression ; [Isoform 2]: Has an angiostatic activity.
• KEGG Pathway: Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway: Cytosolic tRNA aminoacylation (R-HSA-379716)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuronopathy, distal hereditary motor, type 9	DIS2OBPK	Strong	Autosomal dominant	[1]
Distal hereditary motor neuropathy	DISGS2ID	Limited	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Tryptophan--tRNA ligase, cytoplasmic affects the response to substance of Mitoxantrone.	[32]

37 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 Tryptophan--tRNA ligase, cytoplasmic.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tryptophan--tRNA ligase, cytoplasmic.	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[16]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[10]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[17]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[18]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[9]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[9]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of Tryptophan--tRNA ligase, cytoplasmic.	[9]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[19]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[20]
Estrone	DM5T6US	Approved	Estrone increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[10]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[22]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[5]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[27]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[28]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[29]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[30]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[22]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Tryptophan--tRNA ligase, cytoplasmic.	[31]

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 affects the methylation of Tryptophan--tRNA ligase, cytoplasmic.	[24]

References

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