Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9WXH5N)

• DOT Name: Isoleucine--tRNA ligase, cytoplasmic (IARS1)
• Synonyms: EC 6.1.1.5; Isoleucyl-tRNA synthetase; IRS; IleRS
• Gene Name: IARS1
• Related Disease:
  Bacteremia
  Hyperglycemia
  Metabolic disorder
  Prostate cancer
  Prostate carcinoma
  Abdominal aortic aneurysm
  Advanced cancer
  Alzheimer disease
  Carcinoma
  Colorectal carcinoma
  Graves disease
  Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy
  Hematologic disease
  Hyperinsulinemia
  Hypertrophic cardiomyopathy
  Insomnia
  Isolated congenital microcephaly
  Malaria
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Pancreatic cancer
  Polycystic ovarian syndrome
  Psoriasis
  Schizophrenia
  Type-1/2 diabetes
  Adult glioblastoma
  Breast cancer
  Glioblastoma multiforme
  Lipid metabolism disorder
  Methicillin-resistant staphylococci infection
  Breast carcinoma
  Coronary heart disease
  Neuroblastoma
  T-cell acute lymphoblastic leukaemia
  Tuberculosis
• UniProt ID: SYIC_HUMAN
• EC Number: 6.1.1.5
• Pfam ID: PF08264 ; PF19302 ; PF00133
• Sequence:
  MLQQVPENINFPAEEEKILEFWTEFNCFQECLKQSKHKPKFTFYDGPPFATGLPHYGHIL
  AGTIKDIVTRYAHQSGFHVDRRFGWDCHGLPVEYEIDKTLGIRGPEDVAKMGITEYNNQC
  RAIVMRYSAEWKSTVSRLGRWIDFDNDYKTLYPQFMESVWWVFKQLYDKGLVYRGVKVMP
  FSTACNTPLSNFESHQNYKDVQDPSVFVTFPLEEDETVSLVAWTTTPWTLPSNLAVCVNP
  EMQYVKIKDVARGRLLILMEARLSALYKLESDYEILERFPGAYLKGKKYRPLFDYFLKCK
  ENGAFTVLVDNYVKEEEGTGVVHQAPYFGAEDYRVCMDFNIIRKDSLPVCPVDASGCFTT
  EVTDFAGQYVKDADKSIIRTLKEQGRLLVATTFTHSYPFCWRSDTPLIYKAVPSWFVRVE
  NMVDQLLRNNDLCYWVPELVREKRFGNWLKDARDWTISRNRYWGTPIPLWVSDDFEEVVC
  IGSVAELEELSGAKISDLHRESVDHLTIPSRCGKGSLHRISEVFDCWFESGSMPYAQVHY
  PFENKREFEDAFPADFIAEGIDQTRGWFYTLLVLATALFGQPPFKNVIVNGLVLASDGQK
  MSKRKKNYPDPVSIIQKYGADALRLYLINSPVVRAENLRFKEEGVRDVLKDVLLPWYNAY
  RFLIQNVLRLQKEEEIEFLYNENTVRESPNITDRWILSFMQSLIGFFETEMAAYRLYTVV
  PRLVKFVDILTNWYVRMNRRRLKGENGMEDCVMALETLFSVLLSLCRLMAPYTPFLTELM
  YQNLKVLIDPVSVQDKDTLSIHYLMLPRVREELIDKKTESAVSQMQSVIELGRVIRDRKT
  IPIKYPLKEIVVIHQDPEALKDIKSLEKYIIEELNVRKVTLSTDKNKYGIRLRAEPDHMV
  LGKRLKGAFKAVMTSIKQLSSEELEQFQKTGTIVVEGHELHDEDIRLMYTFDQATGGTAQ
  FEAHSDAQALVLLDVTPDQSMVDEGMAREVINRIQKLRKKCNLVPTDEITVYYKAKSEGT
  YLNSVIESHTEFIFTTIKAPLKPYPVSPSDKVLIQEKTQLKGSELEITLTRGSSLPGPAC
  AYVNLNICANGSEQGGVLLLENPKGDNRLDLLKLKSVVTSIFGVKNTELAVFHDETEIQN
  QTDLLSLSGKTLCVTAGSAPSLINSSSTLLCQYINLQLLNAKPQECLMGTVGTLLLENPL
  GQNGLTHQGLLYEAAKVFGLRSRKLKLFLNETQTQEITEDIPVKTLNMKTVYVSVLPTTA
  DF
• Function: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.
• Tissue Specificity: Expressed in liver and muscle (at protein level).
• KEGG Pathway: Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway:
  Cytosolic tRNA aminoacylation (R-HSA-379716)
  Selenoamino acid metabolism (R-HSA-2408522)

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[2]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[3]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[4]
Abdominal aortic aneurysm	DISD06OF	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Graves disease	DISU4KOQ	Strong	Altered Expression	[10]
Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy	DIS7UNOI	Strong	Autosomal recessive	[11]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[12]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[13]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Genetic Variation	[14]
Insomnia	DIS0AFR7	Strong	Altered Expression	[15]
Isolated congenital microcephaly	DISUXHZ6	Strong	Biomarker	[11]
Malaria	DISQ9Y50	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Genetic Variation	[19]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[20]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[21]
Psoriasis	DIS59VMN	Strong	Biomarker	[22]
Schizophrenia	DISSRV2N	Strong	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[24]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[25]
Breast cancer	DIS7DPX1	moderate	Biomarker	[26]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[25]
Lipid metabolism disorder	DISEOA7S	moderate	Altered Expression	[27]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[28]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[26]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[29]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[30]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Altered Expression	[31]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[32]

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 Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[39]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[41]
Marinol	DM70IK5	Approved	Marinol increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[42]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[43]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[44]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[45]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[46]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[37]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[37]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[37]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[37]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[37]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[47]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[48]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[53]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[54]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[49]

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 Isoleucine--tRNA ligase, cytoplasmic (IARS1).	[50]

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