Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXF0B09)

• DOT Name: Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2)
• Synonyms: Eukaryotic translation initiation factor 2 subunit beta; eIF2-beta
• Gene Name: EIF2S2
• Related Disease:
  Cognitive impairment
  Leishmaniasis
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Brain disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cerebellar ataxia
  Chagas disease
  Colorectal carcinoma
  Diffuse systemic sclerosis
  Familial adenomatous polyposis
  Fatty liver disease
  Intellectual disability
  Liposarcoma
  Liver cirrhosis
  MEHMO syndrome
  Non-small-cell lung cancer
  Obesity
  Schizophrenia
  Scleroderma
  Systemic sclerosis
  Carcinoma of liver and intrahepatic biliary tract
  Female hypogonadism
  Liver cancer
  Myotonic dystrophy type 2
  Type-1/2 diabetes
  Wolcott-Rallison syndrome
  Melanoma
  Neoplasm
  Nervous system disease
  Parkinson disease
• UniProt ID: IF2B_HUMAN
• PDB ID: 6K71; 6K72; 6YBV; 6ZMW; 6ZP4; 7A09; 7D43; 7QP6; 8PPL
• Pfam ID: PF01873
• Sequence:
  MSGDEMIFDPTMSKKKKKKKKPFMLDEEGDTQTEETQPSETKEVEPEPTEDKDLEADEED
  TRKKDASDDLDDLNFFNQKKKKKKTKKIFDIDEAEEGVKDLKIESDVQEPTEPEDDLDIM
  LGNKKKKKKNVKFPDEDEILEKDEALEDEDNKKDDGISFSNQTGPAWAGSERDYTYEELL
  NRVFNIMREKNPDMVAGEKRKFVMKPPQVVRVGTKKTSFVNFTDICKLLHRQPKHLLAFL
  LAELGTSGSIDGNNQLVIKGRFQQKQIENVLRRYIKEYVTCHTCRSPDTILQKDTRLYFL
  QCETCHSRCSVASIKTGFQAVTGKRAQLRAKAN
• Function: Component of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B.
• Reactome Pathway:
  PERK regulates gene expression (R-HSA-381042)
  ABC-family proteins mediated transport (R-HSA-382556)
  Translation initiation complex formation (R-HSA-72649)
  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)
  Recycling of eIF2 (R-HSA-72731)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Response of EIF2AK1 (HRI) to heme deficiency (R-HSA-9648895)
  PKR-mediated signaling (R-HSA-9833482)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Posttranslational Modification	[1]
Leishmaniasis	DISABTW7	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Brain disease	DIS6ZC3X	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[9]
Chagas disease	DIS8KNVF	Strong	Posttranslational Modification	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Diffuse systemic sclerosis	DISYF5LP	Strong	Biomarker	[12]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[13]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[14]
Intellectual disability	DISMBNXP	Strong	Biomarker	[15]
Liposarcoma	DIS8IZVM	Strong	Biomarker	[16]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[14]
MEHMO syndrome	DISPH301	Strong	Genetic Variation	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Schizophrenia	DISSRV2N	Strong	Biomarker	[20]
Scleroderma	DISVQ342	Strong	Biomarker	[12]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[12]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[21]
Female hypogonadism	DISWASB4	moderate	Biomarker	[22]
Liver cancer	DISDE4BI	moderate	Biomarker	[21]
Myotonic dystrophy type 2	DIS5ZWF1	moderate	Altered Expression	[23]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[24]
Wolcott-Rallison syndrome	DISKVKXN	moderate	Genetic Variation	[24]
Melanoma	DIS1RRCY	Limited	Biomarker	[25]
Neoplasm	DISZKGEW	Limited	Biomarker	[26]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[27]
Parkinson disease	DISQVHKL	Limited	Biomarker	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[31]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[32]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[34]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[35]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[36]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[34]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[37]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[38]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[42]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[47]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[48]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[49]

4 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 decreases the methylation of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[43]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2).	[43]

References

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