Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4ZSEEE)

• DOT Name: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
• Synonyms: IGF2 mRNA-binding protein 2; IMP-2; Hepatocellular carcinoma autoantigen p62; IGF-II mRNA-binding protein 2; VICKZ family member 2
• Gene Name: IGF2BP2
• Related Disease:
  Adult glioblastoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Ovarian cancer
  Ovarian neoplasm
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adenoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiovascular disease
  Childhood acute lymphoblastic leukemia
  Colon cancer
  Colon carcinoma
  Eclampsia
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Hepatocellular carcinoma
  High blood pressure
  leukaemia
  Leukemia
  Liposarcoma
  Liver cirrhosis
  Matthew-Wood syndrome
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Pancreatic ductal carcinoma
  Pancreatic tumour
  Schizophrenia
  Soft tissue neoplasm
  Triple negative breast cancer
  Fatty liver disease
  Gastric cancer
  Polycystic ovarian syndrome
  Stomach cancer
  Colorectal carcinoma
  Diabetic kidney disease
  Gallbladder carcinoma
  Hyperglycemia
  Lymphoma
  Pancreatic cancer
  Prediabetes syndrome
  Type-1 diabetes
  Type-1/2 diabetes
  Obsolete diabetes mellitus, noninsulin-dependent
• UniProt ID: IF2B2_HUMAN
• PDB ID: 2CQH; 6ROL; 7Q98; 7Q99
• Pfam ID: PF00013 ; PF00076
• Sequence:
  MMNKLYIGNLSPAVTADDLRQLFGDRKLPLAGQVLLKSGYAFVDYPDQNWAIRAIETLSG
  KVELHGKIMEVDYSVSKKLRSRKIQIRNIPPHLQWEVLDGLLAQYGTVENVEQVNTDTET
  AVVNVTYATREEAKIAMEKLSGHQFENYSFKISYIPDEEVSSPSPPQRAQRGDHSSREQG
  HAPGGTSQARQIDFPLRILVPTQFVGAIIGKEGLTIKNITKQTQSRVDIHRKENSGAAEK
  PVTIHATPEGTSEACRMILEIMQKEADETKLAEEIPLKILAHNGLVGRLIGKEGRNLKKI
  EHETGTKITISSLQDLSIYNPERTITVKGTVEACASAEIEIMKKLREAFENDMLAVNQQA
  NLIPGLNLSALGIFSTGLSVLSPPAGPRGAPPAAPYHPFTTHSGYFSSLYPHHQFGPFPH
  HHSYPEQEIVNLFIPTQAVGAIIGKKGAHIKQLARFAGASIKIAPAEGPDVSERMVIITG
  PPEAQFKAQGRIFGKLKEENFFNPKEEVKLEAHIRVPSSTAGRVIGKGGKTVNELQNLTS
  AEVIVPRDQTPDENEEVIVRIIGHFFASQTAQRKIREIVQQVKQQEQKYPQGVASQRSK
• Function: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD.
• Tissue Specificity: Expressed in oocytes, granulosa cells of small and growing follicles, Leydig cells, spermatogonia and semen (at protein level). Expressed in testicular cancer (at protein level). Expressed weakly in heart, placenta, skeletal muscle, bone marrow, colon, kidney, salivary glands, testis and pancreas. Detected in fetal liver, fetal ovary, gonocytes and interstitial cells of the testis.
• Reactome Pathway: Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA (R-HSA-428359)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[4]
Adenoma	DIS78ZEV	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Eclampsia	DISWPO8U	Strong	Altered Expression	[10]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
Head and neck cancer	DISBPSQZ	Strong	Altered Expression	[12]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[13]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[8]
leukaemia	DISS7D1V	Strong	Biomarker	[3]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Liposarcoma	DIS8IZVM	Strong	Altered Expression	[14]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[15]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[18]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[16]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[19]
Schizophrenia	DISSRV2N	Strong	Biomarker	[20]
Soft tissue neoplasm	DISP2OHE	Strong	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[21]
Fatty liver disease	DIS485QZ	moderate	Genetic Variation	[15]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[22]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Altered Expression	[23]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[22]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[24]
Diabetic kidney disease	DISJMWEY	Limited	Genetic Variation	[25]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[26]
Hyperglycemia	DIS0BZB5	Limited	Genetic Variation	[27]
Lymphoma	DISN6V4S	Limited	Altered Expression	[28]
Pancreatic cancer	DISJC981	Limited	Biomarker	[29]
Prediabetes syndrome	DISH2I53	Limited	Genetic Variation	[30]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[25]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[31]
Obsolete diabetes mellitus, noninsulin-dependent	DISS46MZ	No Known	Unknown	[32]

5 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 Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[33]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[41]

10 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 Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[40]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[42]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[45]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).	[46]

References

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