Details of Drug Off-Target (DOT)

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

• DOT Name: Pleckstrin-2 (PLEK2)
• Gene Name: PLEK2
• Related Disease:
  Lung adenocarcinoma
  Major depressive disorder
  Melanoma
  Non-small-cell lung cancer
  Prostate cancer
  Prostate neoplasm
  Gallbladder cancer
  Gallbladder carcinoma
  Neoplasm
  Myeloproliferative neoplasm
• UniProt ID: PLEK2_HUMAN
• PDB ID: 1X1G
• Pfam ID: PF00610 ; PF00169
• Sequence:
  MEDGVLKEGFLVKRGHIVHNWKARWFILRQNTLVYYKLEGGRRVTPPKGRILLDGCTITC
  PCLEYENRPLLIKLKTQTSTEYFLEACSREERDAWAFEITGAIHAGQPGKVQQLHSLRNS
  FKLPPHISLHRIVDKMHDSNTGIRSSPNMEQGSTYKKTFLGSSLVDWLISNSFTASRLEA
  VTLASMLMEENFLRPVGVRSMGAIRSGDLAEQFLDDSTALYTFAESYKKKISPKEEISLS
  TVELSGTVVKQGYLAKQGHKRKNWKVRRFVLRKDPAFLHYYDPSKEENRPVGGFSLRGSL
  VSALEDNGVPTGVKGNVQGNLFKVITKDDTHYYIQASSKAERAEWIEAIKKLT
• Function: May help orchestrate cytoskeletal arrangement. Contribute to lamellipodia formation.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[5]
Gallbladder cancer	DISXJUAF	Disputed	Biomarker	[6]
Gallbladder carcinoma	DISD6ACL	Disputed	Biomarker	[6]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[6]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Pleckstrin-2 (PLEK2) decreases the response to substance of Arsenic trioxide.	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pleckstrin-2 (PLEK2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pleckstrin-2 (PLEK2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Pleckstrin-2 (PLEK2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pleckstrin-2 (PLEK2).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Pleckstrin-2 (PLEK2).	[12]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Pleckstrin-2 (PLEK2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Pleckstrin-2 (PLEK2).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Pleckstrin-2 (PLEK2).	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Pleckstrin-2 (PLEK2).	[16]

References

• [1] Drug-resistant CXCR4-positive cells have the molecular characteristics of EMT in NSCLC.Gene. 2016 Dec 5;594(1):23-29. doi: 10.1016/j.gene.2016.08.043. Epub 2016 Aug 28.
• [2] Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.Mol Psychiatry. 2020 Jul;25(7):1420-1429. doi: 10.1038/s41380-018-0336-6. Epub 2019 Jan 9.
• [3] Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.PLoS One. 2011;6(6):e20971. doi: 10.1371/journal.pone.0020971. Epub 2011 Jun 15.
• [4] PLEK2 mediates metastasis and vascular invasion via the ubiquitin-dependent degradation of SHIP2 in non-small cell lung cancer.Int J Cancer. 2020 May 1;146(9):2563-2575. doi: 10.1002/ijc.32675. Epub 2019 Nov 6.
• [5] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [6] PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway.J Exp Clin Cancer Res. 2019 Jun 10;38(1):247. doi: 10.1186/s13046-019-1250-8.
• [7] Loss of pleckstrin-2 reverts lethality and vascular occlusions in JAK2V617F-positive myeloproliferative neoplasms.J Clin Invest. 2018 Jan 2;128(1):125-140. doi: 10.1172/JCI94518. Epub 2017 Nov 20.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] 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.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [16] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [17] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.