Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0HJREB)

• DOT Name: Kinesin-like protein KIF3B (KIF3B)
• Synonyms: HH0048; Microtubule plus end-directed kinesin motor 3B
• Gene Name: KIF3B
• Related Disease:
  Neoplasm
  Colonic disorder
  Colorectal carcinoma
  Familial adenomatous polyposis
  Inflammatory bowel disease
  Perianal crohn disease
  Retinitis pigmentosa 89
  Schizophrenia
  Seminoma
  Ciliopathy
  Hepatocellular carcinoma
  Advanced cancer
  Squamous cell carcinoma
• UniProt ID: KIF3B_HUMAN
• PDB ID: 3B6U
• Pfam ID: PF00225
• Sequence:
  MSKLKSSESVRVVVRCRPMNGKEKAASYDKVVDVDVKLGQVSVKNPKGTAHEMPKTFTFD
  AVYDWNAKQFELYDETFRPLVDSVLQGFNGTIFAYGQTGTGKTYTMEGIRGDPEKRGVIP
  NSFDHIFTHISRSQNQQYLVRASYLEIYQEEIRDLLSKDQTKRLELKERPDTGVYVKDLS
  SFVTKSVKEIEHVMNVGNQNRSVGATNMNEHSSRSHAIFVITIECSEVGLDGENHIRVGK
  LNLVDLAGSERQAKTGAQGERLKEATKINLSLSALGNVISALVDGKSTHIPYRDSKLTRL
  LQDSLGGNAKTVMVANVGPASYNVEETLTTLRYANRAKNIKNKPRVNEDPKDALLREFQE
  EIARLKAQLEKRSIGRRKRREKRREGGGSGGGGEEEEEEGEEGEEEGDDKDDYWREQQEK
  LEIEKRAIVEDHSLVAEEKMRLLKEKEKKMEDLRREKDAAEMLGAKIKAMESKLLVGGKN
  IVDHTNEQQKILEQKRQEIAEQKRREREIQQQMESRDEETLELKETYSSLQQEVDIKTKK
  LKKLFSKLQAVKAEIHDLQEEHIKERQELEQTQNELTRELKLKHLIIENFIPLEEKSKIM
  NRAFFDEEEDHWKLHPITRLENQQMMKRPVSAVGYKRPLSQHARMSMMIRPEARYRAENI
  VLLELDMPSRTTRDYEGPAIAPKVQAALDAALQDEDEIQVDASSFESTANKKSKARPKSG
  RKSGSSSSSSGTPASQLYPQSRGLVPK
• Function: Microtubule-based molecular motor that transport intracellular cargos, such as vesicles, organelles and protein complexes. Uses ATP hydrolysis to generate force to bind and move along the microtubule. Plays a role in cilia formation. Involved in photoreceptor integrity and opsin trafficking in rod photoreceptors. Transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit GRIN2A into neuronal dendrites.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Intraflagellar transport (R-HSA-5620924)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Kinesins (R-HSA-983189)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Colonic disorder	DISXXS3L	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[2]
Perianal crohn disease	DISOV578	Strong	Biomarker	[2]
Retinitis pigmentosa 89	DIS8MZMJ	Strong	Autosomal dominant	[5]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[6]
Ciliopathy	DIS10G4I	Moderate	Autosomal dominant	[5]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[7]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Kinesin-like protein KIF3B (KIF3B).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Kinesin-like protein KIF3B (KIF3B).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Kinesin-like protein KIF3B (KIF3B).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Kinesin-like protein KIF3B (KIF3B).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Kinesin-like protein KIF3B (KIF3B).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Kinesin-like protein KIF3B (KIF3B).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Kinesin-like protein KIF3B (KIF3B).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Kinesin-like protein KIF3B (KIF3B).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Kinesin-like protein KIF3B (KIF3B).	[19]

2 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 Kinesin-like protein KIF3B (KIF3B).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Kinesin-like protein KIF3B (KIF3B).	[18]

References

• [1] KIF3B Promotes the Proliferation of Pancreatic Cancer.Cancer Biother Radiopharm. 2019 Aug;34(6):355-361. doi: 10.1089/cbr.2018.2716. Epub 2019 Jun 3.
• [2] Perianal Crohn's Disease is Associated with Distal Colonic Disease, Stricturing Disease Behavior, IBD-Associated Serologies and Genetic Variation in the JAK-STAT Pathway.Inflamm Bowel Dis. 2016 Apr;22(4):862-9. doi: 10.1097/MIB.0000000000000705.
• [3] LEF-AS1 participates in occurrence of colorectal cancer through adsorbing miR-505 and promoting KIF3B expression.Eur Rev Med Pharmacol Sci. 2019 Nov;23(21):9362-9370. doi: 10.26355/eurrev_201911_19429.
• [4] Kinesin Kif3b mutation reduces NMDAR subunit NR2A trafficking and causes schizophrenia-like phenotypes in mice.EMBO J. 2020 Jan 2;39(1):e101090. doi: 10.15252/embj.2018101090. Epub 2019 Nov 20.
• [5] Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. Am J Hum Genet. 2020 Jun 4;106(6):893-904. doi: 10.1016/j.ajhg.2020.04.005. Epub 2020 May 7.
• [6] A novel role of KIF3b in the seminoma cell cycle.Exp Cell Res. 2017 Mar 1;352(1):95-103. doi: 10.1016/j.yexcr.2017.01.023. Epub 2017 Feb 1.
• [7] Simul-seq: combined DNA and RNA sequencing for whole-genome and transcriptome profiling.Nat Methods. 2016 Nov;13(11):953-958. doi: 10.1038/nmeth.4028. Epub 2016 Oct 10.
• [8] MiR-127-3p targets KIF3B to inhibit the development of oral squamous cell carcinoma.Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):630-640. doi: 10.26355/eurrev_201901_16877.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [15] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.