Details of Drug Off-Target (DOT)

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

• DOT Name: Eukaryotic translation initiation factor 3 subunit K (EIF3K)
• Synonyms: eIF3k; Eukaryotic translation initiation factor 3 subunit 12; Muscle-specific gene M9 protein; PLAC-24; eIF-3 p25; eIF-3 p28
• Gene Name: EIF3K
• Related Disease:
  LambertEaton myasthenic syndrome
  Nemaline myopathy
  Advanced cancer
  Cardiac failure
  Cerebral palsy
  Congenital myopathy
  Congestive heart failure
  Duchenne muscular dystrophy
  facioscapulohumeral muscular dystrophy
  Glioma
  Hepatocellular carcinoma
  Knee osteoarthritis
  Limb-girdle muscular dystrophy
  Malignant hyperthermia of anesthesia
  Neoplasm
  Neuromuscular disease
  Neuromyelitis optica
  Non-insulin dependent diabetes
  Osteoporosis
  Ptosis
  Rhabdomyosarcoma
  Spinal muscular atrophy
  Autosomal recessive limb-girdle muscular dystrophy type 2D
  Congenital myasthenic syndrome
  Emery-Dreifuss muscular dystrophy
  Peripheral arterial disease
  Amyotrophic lateral sclerosis
  Adult lymphoma
  Lymphoma
  Pediatric lymphoma
• UniProt ID: EIF3K_HUMAN
• PDB ID: 1RZ4; 3J8B; 3J8C; 6FEC; 6YBD; 6ZMW; 6ZON; 6ZP4; 6ZVJ; 7A09; 7QP6; 7QP7; 8PPL
• Pfam ID: PF10075
• Sequence:
  MAMFEQMRANVGKLLKGIDRYNPENLATLERYVETQAKENAYDLEANLAVLKLYQFNPAF
  FQTTVTAQILLKALTNLPHTDFTLCKCMIDQAHQEERPIRQILYLGDLLETCHFQAFWQA
  LDENMDLLEGITGFEDSVRKFICHVVGITYQHIDRWLLAEMLGDLSDSQLKVWMSKYGWS
  ADESGQIFICSQEESIKPKNIVEKIDFDSVSSIMASSQ
• Function: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.
• Tissue Specificity: Ubiquitous, with the highest levels of expression in brain, testis and kidney.
• Reactome Pathway:
  Translation initiation complex formation (R-HSA-72649)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
LambertEaton myasthenic syndrome	DISN0Q7Q	Definitive	Biomarker	[1]
Nemaline myopathy	DIS5IYLY	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Cerebral palsy	DIS82ODL	Strong	Altered Expression	[5]
Congenital myopathy	DISLSK9G	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Altered Expression	[7]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Knee osteoarthritis	DISLSNBJ	Strong	Biomarker	[11]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Posttranslational Modification	[12]
Malignant hyperthermia of anesthesia	DISYC9XI	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[10]
Neuromuscular disease	DISQTIJZ	Strong	Biomarker	[14]
Neuromyelitis optica	DISBFGKL	Strong	Biomarker	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[3]
Osteoporosis	DISF2JE0	Strong	Biomarker	[16]
Ptosis	DISJZNIY	Strong	Biomarker	[17]
Rhabdomyosarcoma	DISNR7MS	Strong	Biomarker	[18]
Spinal muscular atrophy	DISTLKOB	Strong	Genetic Variation	[19]
Autosomal recessive limb-girdle muscular dystrophy type 2D	DISRD6EW	moderate	Altered Expression	[20]
Congenital myasthenic syndrome	DISJLG2T	moderate	Genetic Variation	[21]
Emery-Dreifuss muscular dystrophy	DISYTPR5	moderate	Posttranslational Modification	[12]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[22]
Amyotrophic lateral sclerosis	DISF7HVM	Disputed	Biomarker	[23]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[24]
Lymphoma	DISN6V4S	Limited	Biomarker	[24]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[24]

4 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 Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[25]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[30]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[27]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[34]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone affects the splicing of Eukaryotic translation initiation factor 3 subunit K (EIF3K).	[35]

References

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