Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCU9FS5)

• DOT Name: tRNA dimethylallyltransferase (TRIT1)
• Synonyms: EC 2.5.1.75; Isopentenyl-diphosphate:tRNA isopentenyltransferase; IPP transferase; IPPT; hGRO1; tRNA isopentenyltransferase 1; IPTase
• Gene Name: TRIT1
• Related Disease:
  Attention deficit hyperactivity disorder
  Lung adenocarcinoma
  Mitochondrial disease
  Advanced cancer
  Alzheimer disease
  Anemia
  Breast cancer
  Breast carcinoma
  Combined oxidative phosphorylation deficiency 35
  Depression
  Familial dilated cardiomyopathy
  Gastric cancer
  Idiopathic thrombocytopenic purpura
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Oral cancer
  Squamous cell carcinoma
  Stomach cancer
  Tuberculosis
  Typhus
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Ovarian cancer
  Ovarian neoplasm
  Nematode infection
  Post-traumatic stress disorder
  Precancerous condition
• UniProt ID: MOD5_HUMAN
• EC Number: 2.5.1.75
• Pfam ID: PF01715
• Sequence:
  MASVAAARAVPVGSGLRGLQRTLPLVVILGATGTGKSTLALQLGQRLGGEIVSADSMQVY
  EGLDIITNKVSAQEQRICRHHMISFVDPLVTNYTVVDFRNRATALIEDIFARDKIPIVVG
  GTNYYIESLLWKVLVNTKPQEMGTEKVIDRKVELEKEDGLVLHKRLSQVDPEMAAKLHPH
  DKRKVARSLQVFEETGISHSEFLHRQHTEEGGGPLGGPLKFSNPCILWLHADQAVLDERL
  DKRVDDMLAAGLLEELRDFHRRYNQKNVSENSQDYQHGIFQSIGFKEFHEYLITEGKCTL
  ETSNQLLKKGIEALKQVTKRYARKQNRWVKNRFLSRPGPIVPPVYGLEVSDVSKWEESVL
  EPALEIVQSFIQGHKPTATPIKMPYNEAENKRSYHLCDLCDRIIIGDREWAAHIKSKSHL
  NQLKKRRRLDSDAVNTIESQSVSPDHNKEPKEKGSPGQNDQELKCSV
• Function: Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37 of both cytosolic and mitochondrial tRNAs, leading to the formation of N6-(dimethylallyl)adenosine (i6A37). Mediates modification of a limited subset of tRNAs: tRNA(Ser)(AGA), tRNA(Ser)(CGA), tRNA(Ser)(UGA), as well as partial modification of the selenocysteine tRNA(Ser)(UCA). TRIT1 is therefore required for selenoprotein expression.
• KEGG Pathway: Metabolic pathways (hsa01100)
• Reactome Pathway:
  tRNA modification in the mitochondrion (R-HSA-6787450)
  tRNA modification in the nucleus and cytosol (R-HSA-6782315)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Definitive	Genetic Variation	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Genetic Variation	[2]
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Anemia	DISTVL0C	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Combined oxidative phosphorylation deficiency 35	DIS4XHR1	Strong	Autosomal recessive	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Familial dilated cardiomyopathy	DISBHDU9	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[11]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Lung neoplasm	DISVARNB	Strong	Biomarker	[14]
Melanoma	DIS1RRCY	Strong	Biomarker	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Oral cancer	DISLD42D	Strong	Altered Expression	[15]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[18]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[11]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[19]
Typhus	DISJ5JX1	Strong	Biomarker	[20]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[21]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[4]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[21]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[21]
Nematode infection	DISVFLRK	Limited	Biomarker	[22]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[23]
Precancerous condition	DISV06FL	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[28]
Selenium	DM25CGV	Approved	Selenium decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[30]
Aspirin	DM672AH	Approved	Aspirin increases the expression of tRNA dimethylallyltransferase (TRIT1).	[31]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of tRNA dimethylallyltransferase (TRIT1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of tRNA dimethylallyltransferase (TRIT1).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of tRNA dimethylallyltransferase (TRIT1).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of tRNA dimethylallyltransferase (TRIT1).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of tRNA dimethylallyltransferase (TRIT1).	[34]

References

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