Details of Drug Off-Target (DOT)

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

• DOT Name: Histidine--tRNA ligase, cytoplasmic (HARS1)
• Synonyms: EC 6.1.1.21; Histidyl-tRNA synthetase; HisRS
• Gene Name: HARS1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Advanced cancer
  Allergic rhinitis
  Alzheimer disease
  Arrhythmia
  Atrial fibrillation
  Autoimmune disease
  Autosomal dominant Charcot-Marie-Tooth disease type 2W
  Cardiomyopathy
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Cognitive impairment
  Colon carcinoma
  Dementia
  Depression
  Epithelial ovarian cancer
  Hepatitis C virus infection
  Idiopathic inflammatory myopathy
  Liver cirrhosis
  Mental disorder
  Mixed anxiety and depressive disorder
  Myopathy
  Myositis disease
  Non-insulin dependent diabetes
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Papillary renal cell carcinoma
  Peripheral arterial disease
  Peripheral neuropathy
  Polymyositis
  Prostate cancer
  Renal cell carcinoma
  Rheumatoid arthritis
  Usher syndrome
  Usher syndrome type 3B
  Alcohol dependence
  Movement disorder
  Schwannoma
  Usher syndrome type 3
  Nervous system disease
  Neurofibromatosis type 2
  Pulmonary disease
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: HARS1_HUMAN
• PDB ID: 1X59; 2LW7; 4G84; 4G85; 4PHC; 4X5O; 5W6M; 6O76
• EC Number: 6.1.1.21
• Pfam ID: PF03129 ; PF13393 ; PF00458
• Sequence:
  MAERAALEELVKLQGERVRGLKQQKASAELIEEEVAKLLKLKAQLGPDESKQKFVLKTPK
  GTRDYSPRQMAVREKVFDVIIRCFKRHGAEVIDTPVFELKETLMGKYGEDSKLIYDLKDQ
  GGELLSLRYDLTVPFARYLAMNKLTNIKRYHIAKVYRRDNPAMTRGRYREFYQCDFDIAG
  NFDPMIPDAECLKIMCEILSSLQIGDFLVKVNDRRILDGMFAICGVSDSKFRTICSSVDK
  LDKVSWEEVKNEMVGEKGLAPEVADRIGDYVQQHGGVSLVEQLLQDPKLSQNKQALEGLG
  DLKLLFEYLTLFGIDDKISFDLSLARGLDYYTGVIYEAVLLQTPAQAGEEPLGVGSVAAG
  GRYDGLVGMFDPKGRKVPCVGLSIGVERIFSIVEQRLEALEEKIRTTETQVLVASAQKKL
  LEERLKLVSELWDAGIKAELLYKKNPKLLNQLQYCEEAGIPLVAIIGEQELKDGVIKLRS
  VTSREEVDVRREDLVEEIKRRTGQPLCIC
• Function: Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP). Plays a role in axon guidance.
• Tissue Specificity: Brain, heart, liver and kidney.
• KEGG Pathway: Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway: Cytosolic tRNA aminoacylation (R-HSA-379716)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Allergic rhinitis	DIS3U9HN	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[5]
Arrhythmia	DISFF2NI	Strong	Altered Expression	[6]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[7]
Autoimmune disease	DISORMTM	Strong	Biomarker	[8]
Autosomal dominant Charcot-Marie-Tooth disease type 2W	DISVY2DP	Strong	Autosomal dominant	[9]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Cognitive impairment	DISH2ERD	Strong	Genetic Variation	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Dementia	DISXL1WY	Strong	Genetic Variation	[5]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[16]
Idiopathic inflammatory myopathy	DISGB1BZ	Strong	Biomarker	[17]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[18]
Mental disorder	DIS3J5R8	Strong	Biomarker	[19]
Mixed anxiety and depressive disorder	DISV809X	Strong	Biomarker	[19]
Myopathy	DISOWG27	Strong	Biomarker	[20]
Myositis disease	DISCIXF0	Strong	Biomarker	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[15]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[15]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[11]
Peripheral arterial disease	DIS78WFB	Strong	Biomarker	[24]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[12]
Polymyositis	DIS5DHFP	Strong	Biomarker	[25]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[23]
Usher syndrome	DIS9YIS7	Strong	Genetic Variation	[27]
Usher syndrome type 3B	DISPLHUS	Strong	Autosomal recessive	[28]
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[29]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[30]
Schwannoma	DISTTVLA	moderate	Altered Expression	[31]
Usher syndrome type 3	DISRAL84	Supportive	Autosomal recessive	[28]
Nervous system disease	DISJ7GGT	Disputed	Genetic Variation	[32]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[33]
Pulmonary disease	DIS6060I	Limited	Biomarker	[8]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[34]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Histidine--tRNA ligase, cytoplasmic (HARS1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Histidine--tRNA ligase, cytoplasmic (HARS1).	[44]

11 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 Histidine--tRNA ligase, cytoplasmic (HARS1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[41]
Selenium	DM25CGV	Approved	Selenium increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[42]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[43]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[43]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[42]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Histidine--tRNA ligase, cytoplasmic (HARS1).	[45]

References

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