Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2WQ6QD)

• DOT Name: Kinesin-like protein KIF2A (KIF2A)
• Synonyms: Kinesin-2; hK2
• Gene Name: KIF2A
• Related Disease:
  Gastric cancer
  Squamous cell carcinoma
  Stomach cancer
  Acute myocardial infarction
  B-cell lymphoma
  Bardet biedl syndrome
  Classic lissencephaly
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Complex cortical dysplasia with other brain malformations 3
  Epithelial ovarian cancer
  Familial adenomatous polyposis
  Glioma
  Gonorrhea
  Head and neck cancer
  Head and neck carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Lissencephaly spectrum disorders
  Lung adenocarcinoma
  Macular corneal dystrophy
  Microlissencephaly
  Nasopharyngeal carcinoma
  Neoplasm
  Neuralgia
  Ovarian cancer
  Ovarian neoplasm
  Prostate carcinoma
  Schizophrenia
  Acute myelogenous leukaemia
  Carcinoma
  Isolated congenital microcephaly
  Lung cancer
  Lung carcinoma
  Malignant tumor of nasopharynx
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Parkinson disease
  Prostate cancer
• UniProt ID: KIF2A_HUMAN
• PDB ID: 2GRY; 6BBN
• Pfam ID: PF00225
• Sequence:
  MATANFGKIQIGIYVEIKRSDGRIHQAMVTSLNEDNESVTVEWIENGDTKGKEIDLESIF
  SLNPDLVPDEEIEPSPETPPPPASSAKVNKIVKNRRTVASIKNDPPSRDNRVVGSARARP
  SQFPEQSSSAQQNGSVSDISPVQAAKKEFGPPSRRKSNCVKEVEKLQEKREKRRLQQQEL
  REKRAQDVDATNPNYEIMCMIRDFRGSLDYRPLTTADPIDEHRICVCVRKRPLNKKETQM
  KDLDVITIPSKDVVMVHEPKQKVDLTRYLENQTFRFDYAFDDSAPNEMVYRFTARPLVET
  IFERGMATCFAYGQTGSGKTHTMGGDFSGKNQDCSKGIYALAARDVFLMLKKPNYKKLEL
  QVYATFFEIYSGKVFDLLNRKTKLRVLEDGKQQVQVVGLQEREVKCVEDVLKLIDIGNSC
  RTSGQTSANAHSSRSHAVFQIILRRKGKLHGKFSLIDLAGNERGADTSSADRQTRLEGAE
  INKSLLALKECIRALGRNKPHTPFRASKLTQVLRDSFIGENSRTCMIATISPGMASCENT
  LNTLRYANRVKELTVDPTAAGDVRPIMHHPPNQIDDLETQWGVGSSPQRDDLKLLCEQNE
  EEVSPQLFTFHEAVSQMVEMEEQVVEDHRAVFQESIRWLEDEKALLEMTEEVDYDVDSYA
  TQLEAILEQKIDILTELRDKVKSFRAALQEEEQASKQINPKRPRAL
• Function: Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Kinesins (R-HSA-983189)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[2]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[4]
Classic lissencephaly	DISR8S3S	Strong	Genetic Variation	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Complex cortical dysplasia with other brain malformations 3	DISWJPFK	Strong	Autosomal dominant	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
Gonorrhea	DISQ5AO6	Strong	Altered Expression	[12]
Head and neck cancer	DISBPSQZ	Strong	Altered Expression	[13]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[13]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Lissencephaly spectrum disorders	DISBCZL7	Strong	Genetic Variation	[5]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Macular corneal dystrophy	DISOLD0H	Strong	Biomarker	[8]
Microlissencephaly	DISUCKNT	Strong	Biomarker	[8]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Neuralgia	DISWO58J	Strong	Altered Expression	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[18]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[19]
Carcinoma	DISH9F1N	moderate	Altered Expression	[20]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[21]
Lung cancer	DISCM4YA	moderate	Altered Expression	[22]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[22]
Malignant tumor of nasopharynx	DISTGIGF	moderate	Biomarker	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[16]
Breast cancer	DIS7DPX1	Limited	Biomarker	[24]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[24]
Parkinson disease	DISQVHKL	Limited	Biomarker	[25]
Prostate cancer	DISF190Y	Limited	Biomarker	[16]

11 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 Kinesin-like protein KIF2A (KIF2A).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Kinesin-like protein KIF2A (KIF2A).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kinesin-like protein KIF2A (KIF2A).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Kinesin-like protein KIF2A (KIF2A).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kinesin-like protein KIF2A (KIF2A).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Kinesin-like protein KIF2A (KIF2A).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Kinesin-like protein KIF2A (KIF2A).	[32]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Kinesin-like protein KIF2A (KIF2A).	[33]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Kinesin-like protein KIF2A (KIF2A).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Kinesin-like protein KIF2A (KIF2A).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Kinesin-like protein KIF2A (KIF2A).	[36]

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 decreases the methylation of Kinesin-like protein KIF2A (KIF2A).	[34]

References

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• [2] Human coronary thrombus formation is associated with degree of plaque disruption and expression of tissue factor and hexokinase II.Circ J. 2015;79(11):2430-8. doi: 10.1253/circj.CJ-15-0394. Epub 2015 Sep 3.
• [3] High KIF2A expression predicts unfavorable prognosis in diffuse large B cell lymphoma.Ann Hematol. 2017 Sep;96(9):1485-1491. doi: 10.1007/s00277-017-3047-1. Epub 2017 Jun 14.
• [4] Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.PLoS Genet. 2016 Dec 8;12(12):e1006469. doi: 10.1371/journal.pgen.1006469. eCollection 2016 Dec.
• [5] Recurrent KIF2A mutations are responsible for classic lissencephaly.Neurogenetics. 2017 Apr;18(2):73-79. doi: 10.1007/s10048-016-0499-8. Epub 2016 Oct 17.
• [6] Downregulation of the hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil.Chemotherapy. 2008;54(5):357-63. doi: 10.1159/000153655. Epub 2008 Sep 5.
• [7] KIF2A overexpression and its association with clinicopathologic characteristics and unfavorable prognosis in colorectal cancer.Tumour Biol. 2015 Nov;36(11):8895-902. doi: 10.1007/s13277-015-3603-z. Epub 2015 Jun 13.
• [8] Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat Genet. 2013 Jun;45(6):639-47. doi: 10.1038/ng.2613. Epub 2013 Apr 21.
• [9] Overexpression of KIF2A is Suppressed by miR-206 and Associated with Poor Prognosis in Ovarian Cancer.Cell Physiol Biochem. 2018;50(3):810-822. doi: 10.1159/000494467. Epub 2018 Oct 23.
• [10] Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.Sci Rep. 2016 Jun 7;6:27456. doi: 10.1038/srep27456.
• [11] Role of KIF2A in the progression and metastasis of human glioma.Mol Med Rep. 2016 Feb;13(2):1781-7. doi: 10.3892/mmr.2015.4700. Epub 2015 Dec 22.
• [12] KIF2A Overexpression and Its Association with Clinicopathologic Characteristics and Poor Prognoses in Patients with Gastric Cancer.Dis Markers. 2016;2016:7484516. doi: 10.1155/2016/7484516. Epub 2016 Sep 28.
• [13] Roles of GLUT-1 and HK-II expression in the biological behavior of head and neck cancer.Oncotarget. 2019 Apr 30;10(32):3066-3083. doi: 10.18632/oncotarget.24684. eCollection 2019 Apr 30.
• [14] Differential association of STAT3 and HK-II expression in hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma.J Med Virol. 2016 Sep;88(9):1552-9. doi: 10.1002/jmv.24498. Epub 2016 Mar 8.
• [15] Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma.Int J Mol Sci. 2019 Mar 14;20(6):1292. doi: 10.3390/ijms20061292.
• [16] Effects of KIF2A on the prognosis of nasopharyngeal carcinoma and nasopharyngeal carcinoma cells.Oncol Lett. 2019 Sep;18(3):2718-2723. doi: 10.3892/ol.2019.10597. Epub 2019 Jul 9.
• [17] KIF2A characterization after spinal cord injury.Cell Mol Life Sci. 2019 Nov;76(21):4355-4368. doi: 10.1007/s00018-019-03116-2. Epub 2019 Apr 30.
• [18] A family-based association study of kinesin heavy chain member 2 gene (KIF2) and schizophrenia.Neurosci Lett. 2006 Oct 23;407(2):151-5. doi: 10.1016/j.neulet.2006.08.025. Epub 2006 Sep 7.
• [19] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [20] Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma.Oncotarget. 2017 Feb 21;8(8):14133-14146. doi: 10.18632/oncotarget.13044.
• [21] Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors.Nat Commun. 2019 Jun 13;10(1):2612. doi: 10.1038/s41467-019-10497-2.
• [22] Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells.Oncogene. 2014 Nov 20;33(47):5457-66. doi: 10.1038/onc.2013.486. Epub 2013 Nov 18.
• [23] Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.Int J Cancer. 2003 Aug 20;106(2):244-51. doi: 10.1002/ijc.11208.
• [24] Down-regulation of KIF2A inhibits gastric cancer cell invasion via suppressing MT1-MMP.Clin Exp Pharmacol Physiol. 2018 Oct;45(10):1010-1018. doi: 10.1111/1440-1681.12974. Epub 2018 Jun 26.
• [25] TIGAR inclusion pathology is specific for Lewy body diseases.Brain Res. 2019 Mar 1;1706:218-223. doi: 10.1016/j.brainres.2018.09.032. Epub 2018 Sep 26.
• [26] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [27] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [28] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [29] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [30] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [31] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [32] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [33] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [34] 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.
• [35] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [36] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.