Details of Drug Off-Target (DOT)

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

• DOT Name: Cyclin-dependent kinase 5 activator 2 (CDK5R2)
• Synonyms: CDK5 activator 2; Cyclin-dependent kinase 5 regulatory subunit 2; p39; p39I
• Gene Name: CDK5R2
• Related Disease:
  Lung cancer
  Lung carcinoma
  Neoplasm
  Squamous cell carcinoma
  Alzheimer disease
  Brain disease
  Lyme disease
  Matthew-Wood syndrome
  Pancreatic cancer
• UniProt ID: CD5R2_HUMAN
• Pfam ID: PF03261
• Sequence:
  MGTVLSLSPASSAKGRRPGGLPEEKKKAPPAGDEALGGYGAPPVGKGGKGESRLKRPSVL
  ISALTWKRLVAASAKKKKGSKKVTPKPASTGPDPLVQQRNRENLLRKGRDPPDGGGTAKP
  LAVPVPTVPAAAATCEPPSGGSAAAQPPGSGGGKPPPPPPPAPQVAPPVPGGSPRRVIVQ
  ASTGELLRCLGDFVCRRCYRLKELSPGELVGWFRGVDRSLLLQGWQDQAFITPANLVFVY
  LLCRESLRGDELASAAELQAAFLTCLYLAYSYMGNEISYPLKPFLVEPDKERFWQRCLRL
  IQRLSPQMLRLNADPHFFTQVFQDLKNEGEAAASGGGPPSGGAPAASSAARDSCAAGTKH
  WTMNLDR
• Function: Activator of CDK5/TPKII.
• Tissue Specificity: Brain and neuron specific.
• Reactome Pathway: NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Brain disease	DIS6ZC3X	Strong	Biomarker	[2]
Lyme disease	DISO70G5	Strong	Biomarker	[3]
Matthew-Wood syndrome	DISA7HR7	moderate	Altered Expression	[4]
Pancreatic cancer	DISJC981	moderate	Biomarker	[4]

6 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 Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[8]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[9]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[10]

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 increases the methylation of Cyclin-dependent kinase 5 activator 2 (CDK5R2).	[11]

References

• [1] Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.PLoS One. 2018 Nov 19;13(11):e0207483. doi: 10.1371/journal.pone.0207483. eCollection 2018.
• [2] Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease.Neurobiol Aging. 2005 Aug-Sep;26(8):1145-51. doi: 10.1016/j.neurobiolaging.2004.10.003. Epub 2004 Dec 22.
• [3] Proteomics in human disease: cancer, heart and infectious diseases.Electrophoresis. 1999 Jul;20(10):2100-10. doi: 10.1002/(SICI)1522-2683(19990701)20:10<2100::AID-ELPS2100>3.0.CO;2-D.
• [4] Cyclin-dependent kinase 5 is amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras.Clin Cancer Res. 2011 Oct 1;17(19):6140-50. doi: 10.1158/1078-0432.CCR-10-2288. Epub 2011 Aug 8.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [10] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [11] 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.