Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT79PQUN)

• DOT Name: Eukaryotic translation initiation factor 5 (EIF5)
• Synonyms: eIF-5
• Gene Name: EIF5
• Related Disease:
  Malaria
  Male breast carcinoma
  Alzheimer disease
  Chronic hepatitis B virus infection
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Lung adenocarcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Rectal carcinoma
  Schizophrenia
  Hepatitis B virus infection
  Hepatocellular carcinoma
• UniProt ID: IF5_HUMAN
• PDB ID: 2E9H; 2G2K; 2IU1
• Pfam ID: PF01873 ; PF02020
• Sequence:
  MSVNVNRSVSDQFYRYKMPRLIAKVEGKGNGIKTVIVNMVDVAKALNRPPTYPTKYFGCE
  LGAQTQFDVKNDRYIVNGSHEANKLQDMLDGFIKKFVLCPECENPETDLHVNPKKQTIGN
  SCKACGYRGMLDTHHKLCTFILKNPPENSDSGTGKKEKEKKNRKGKDKENGSVSSSETPP
  PPPPPNEINPPPHTMEEEEDDDWGEDTTEEAQRRRMDEISDHAKVLTLSDDLERTIEERV
  NILFDFVKKKKEEGVIDSSDKEIVAEAERLDVKAMGPLVLTEVLFNEKIREQIKKYRRHF
  LRFCHNNKKAQRYLLHGLECVVAMHQAQLISKIPHILKEMYDADLLEEEVIISWSEKASK
  KYVSKELAKEIRVKAEPFIKWLKEAEEESSGGEEEDEDENIEVVYSKAASVPKVETVKSD
  NKDDDIDIDAI
• Function: Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. In this complex, acts as a GTPase-activating protein, by promoting GTP hydrolysis by eIF2G (EIF2S3). During scanning, interacts with both EIF1 (via its C-terminal domain (CTD)) and EIF1A (via its NTD). This interaction with EIF1A contributes to the maintenance of EIF1 within the open 43S PIC. When start codon is recognized, EIF5, via its NTD, induces eIF2G (EIF2S3) to hydrolyze the GTP. Start codon recognition also induces a conformational change of the PIC to a closed state. This change increases the affinity of EIF5-CTD for EIF2-beta (EIF2S2), which allows the release, by an indirect mechanism, of EIF1 from the PIC. Finally, EIF5 stabilizes the PIC in its closed conformation.
• Reactome Pathway:
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Ribosomal scanning and start codon recognition (R-HSA-72702)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Male breast carcinoma	DISUNQ2Q	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[6]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[7]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[7]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Biomarker	[9]
Hepatitis B virus infection	DISLQ2XY	moderate	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[10]

32 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 Eukaryotic translation initiation factor 5 (EIF5).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Eukaryotic translation initiation factor 5 (EIF5).	[21]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Eukaryotic translation initiation factor 5 (EIF5).	[22]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[23]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[24]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[25]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[17]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Eukaryotic translation initiation factor 5 (EIF5).	[22]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[27]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[29]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[17]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[32]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[35]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[39]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[40]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[41]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Eukaryotic translation initiation factor 5 (EIF5).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Eukaryotic translation initiation factor 5 (EIF5).	[19]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of Eukaryotic translation initiation factor 5 (EIF5).	[31]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Eukaryotic translation initiation factor 5 (EIF5).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Eukaryotic translation initiation factor 5 (EIF5).	[19]

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