Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB4GZ0V)

• DOT Name: Eukaryotic translation initiation factor 1 (EIF1)
• Synonyms: eIF1; A121; Protein translation factor SUI1 homolog; Sui1iso1
• Gene Name: EIF1
• Related Disease:
  Asthma
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Endometriosis
  Epithelial ovarian cancer
  Familial multiple trichoepithelioma
  Glomerulonephritis
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Intervertebral disc degeneration
  Liver cirrhosis
  Neoplasm
  Nervous system inflammation
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Rectal carcinoma
  Uveal Melanoma
  Chronic obstructive pulmonary disease
  Parkinson disease
• UniProt ID: EIF1_HUMAN
• PDB ID: 2IF1; 4KZX; 4KZY; 6YBW; 6ZMW; 6ZP4; 6ZVJ; 7A09; 7QP6; 8PPK; 8PPL
• Pfam ID: PF01253
• Sequence:
  MSAIQNLHSFDPFADASKGDDLLPAGTEDYIHIRIQQRNGRKTLTTVQGIADDYDKKKLV
  KAFKKKFACNGTVIEHPEYGEVIQLQGDQRKNICQFLVEIGLAKDDQLKVHGF
• 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. Together with eIF1A (EIF1AX), EIF1 facilitates scanning and is essential for start codon recognition on the basis of AUG nucleotide context and location relative to the 5'-cap. Participates to initiation codon selection by influencing the conformation of the 40S ribosomal subunit and the positions of bound mRNA and initiator tRNA; this is possible after its binding to the interface surface of the platform of the 40S ribosomal subunit close to the P-site. Together with eIF1A (EIF1AX), also regulates the opening and closing of the mRNA binding channel, which ensures mRNA recruitment, scanning and the fidelity of initiation codon selection. Continuously monitors and protects against premature and partial base-pairing of codons in the 5'-UTR with the anticodon of initiator tRNA. Together with eIF1A (EIF1AX), acts for ribosomal scanning, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. Interacts with EIF4G1, which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site. EIF4G1-EIF1 complex promotes ribosome scanning (on both short and long 5'UTR), leaky scanning (on short 5'UTR) which is the bypass of the initial start codon, and discrimination against cap-proximal AUG. Is probably maintained within the 43S PIC in open conformation thanks to eIF1A-EIF5 interaction. Once the correct start codon is reached, EIF1 is physically excluded from the decoding site, shifting the PIC into the closed conformation and arresting it at the start codon.

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Endometriosis	DISX1AG8	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[10]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[11]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Intervertebral disc degeneration	DISG3AIM	Strong	Biomarker	[13]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[7]
Uveal Melanoma	DISA7ZGL	Strong	Genetic Variation	[3]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[17]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[18]

33 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 1 (EIF1).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[24]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[25]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Eukaryotic translation initiation factor 1 (EIF1).	[27]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[28]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Eukaryotic translation initiation factor 1 (EIF1).	[29]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[30]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[31]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[32]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[33]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Eukaryotic translation initiation factor 1 (EIF1).	[27]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[34]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[34]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[34]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Eukaryotic translation initiation factor 1 (EIF1).	[35]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[36]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[37]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[38]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Eukaryotic translation initiation factor 1 (EIF1).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[45]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Eukaryotic translation initiation factor 1 (EIF1).	[46]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[47]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Eukaryotic translation initiation factor 1 (EIF1).	[48]

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 increases the methylation of Eukaryotic translation initiation factor 1 (EIF1).	[40]

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