Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFABY9G)

• DOT Name: Eukaryotic translation initiation factor 3 subunit A (EIF3A)
• Synonyms: eIF3a; Eukaryotic translation initiation factor 3 subunit 10; eIF-3-theta; eIF3 p167; eIF3 p180; eIF3 p185
• Gene Name: EIF3A
• Related Disease:
  Acute myelogenous leukaemia
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Lung adenocarcinoma
  Prostate cancer
  Adenocarcinoma
  Adult glioblastoma
  Amyloidosis
  Astrocytoma
  Bone osteosarcoma
  Brain neoplasm
  Breast neoplasm
  Carcinoma
  Chronic hepatitis B virus infection
  Colorectal carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Myopathy
  Nasopharyngeal carcinoma
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate carcinoma
  Prostate neoplasm
  Pulmonary fibrosis
  Renal fibrosis
  Squamous cell carcinoma
  Stomach cancer
  Autism
  Bladder cancer
  Cervical carcinoma
  Head-neck squamous cell carcinoma
  Intellectual disability
  Neurodevelopmental disorder
  Urinary bladder cancer
  Acute lymphocytic leukaemia
  Invasive ductal breast carcinoma
  Non-small-cell lung cancer
  Parkinson disease
• UniProt ID: EIF3A_HUMAN
• PDB ID: 3J8B; 3J8C; 6YBD; 6YBT; 6ZMW; 6ZON; 6ZP4; 6ZVJ; 7A09; 7QP6; 7QP7; 8PPL
• Pfam ID: PF01399
• Sequence:
  MPAYFQRPENALKRANEFLEVGKKQPALDVLYDVMKSKKHRTWQKIHEPIMLKYLELCVD
  LRKSHLAKEGLYQYKNICQQVNIKSLEDVVRAYLKMAEEKTEAAKEESQQMVLDIEDLDN
  IQTPESVLLSAVSGEDTQDRTDRLLLTPWVKFLWESYRQCLDLLRNNSRVERLYHDIAQQ
  AFKFCLQYTRKAEFRKLCDNLRMHLSQIQRHHNQSTAINLNNPESQSMHLETRLVQLDSA
  ISMELWQEAFKAVEDIHGLFSLSKKPPKPQLMANYYNKVSTVFWKSGNALFHASTLHRLY
  HLSREMRKNLTQDEMQRMSTRVLLATLSIPITPERTDIARLLDMDGIIVEKQRRLATLLG
  LQAPPTRIGLINDMVRFNVLQYVVPEVKDLYNWLEVEFNPLKLCERVTKVLNWVREQPEK
  EPELQQYVPQLQNNTILRLLQQVSQIYQSIEFSRLTSLVPFVDAFQLERAIVDAARHCDL
  QVRIDHTSRTLSFGSDLNYATREDAPIGPHLQSMPSEQIRNQLTAMSSVLAKALEVIKPA
  HILQEKEEQHQLAVTAYLKNSRKEHQRILARRQTIEERKERLESLNIQREKEELEQREAE
  LQKVRKAEEERLRQEAKEREKERILQEHEQIKKKTVRERLEQIKKTELGAKAFKDIDIED
  LEELDPDFIMAKQVEQLEKEKKELQERLKNQEKKIDYFERAKRLEEIPLIKSAYEEQRIK
  DMDLWEQQEEERITTMQLEREKALEHKNRMSRMLEDRDLFVMRLKAARQSVYEEKLKQFE
  ERLAEERHNRLEERKRQRKEERRITYYREKEEEEQRRAEEQMLKEREERERAERAKREEE
  LREYQERVKKLEEVERKKRQRELEIEERERRREEERRLGDSSLSRKDSRWGDRDSEGTWR
  KGPEADSEWRRGPPEKEWRRGEGRDEDRSHRRDEERPRRLGDDEDREPSLRPDDDRVPRR
  GMDDDRGPRRGPEEDRFSRRGADDDRPSWRNTDDDRPPRRIADEDRGNWRHADDDRPPRR
  GLDEDRGSWRTADEDRGPRRGMDDDRGPRRGGADDERSSWRNADDDRGPRRGLDDDRGPR
  RGMDDDRGPRRGMDDDRGPRRGMDDDRGPRRGLDDDRGPWRNADDDRIPRRGAEDDRGPW
  RNMDDDRLSRRADDDRFPRRGDDSRPGPWRPLVKPGGWREKEKAREESWGPPRESRPSEE
  REWDREKERDRDNQDREENDKDPERERDRERDVDREDRFRRPRDEGGWRRGPAEESSSWR
  DSSRRDDRDRDDRRRERDDRRDLRERRDLRDDRDRRGPPLRSEREEVSSWRRADDRKDDR
  VEERDPPRRVPPPALSRDRERDRDREREGEKEKASWRAEKDRESLRRTKNETDEDGWTTV
  RR
• Function: RNA-binding 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 ; (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation ; (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2.
• 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

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Definitive	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[2]
Prostate cancer	DISF190Y	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[5]
Amyloidosis	DISHTAI2	Strong	Biomarker	[6]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Carcinoma	DISH9F1N	Strong	Altered Expression	[10]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Biomarker	[17]
Leukemia	DISNAKFL	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[9]
Myopathy	DISOWG27	Strong	Biomarker	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[20]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[21]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[23]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Biomarker	[26]
Autism	DISV4V1Z	moderate	Biomarker	[27]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[28]
Cervical carcinoma	DIST4S00	moderate	Genetic Variation	[29]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[30]
Intellectual disability	DISMBNXP	moderate	Biomarker	[27]
Neurodevelopmental disorder	DIS372XH	moderate	Biomarker	[27]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[28]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Biomarker	[31]
Invasive ductal breast carcinoma	DIS43J58	Limited	Biomarker	[32]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[33]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Eukaryotic translation initiation factor 3 subunit A (EIF3A) increases the response to substance of Etoposide.	[54]

19 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 Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[41]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[43]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[44]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[45]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[44]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[46]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[47]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[52]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[53]

2 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB increases the metabolism of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[48]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the metabolism of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[49]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Eukaryotic translation initiation factor 3 subunit A (EIF3A).	[49]

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