Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGD9A2A)

• DOT Name: CDK5 and ABL1 enzyme substrate 2 (CABLES2)
• Synonyms: Interactor with CDK3 2; Ik3-2
• Gene Name: CABLES2
• Related Disease:
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Neoplasm
• UniProt ID: CABL2_HUMAN
• Pfam ID: PF00134
• Sequence:
  MAAAAAGGAPGPAPGPAGPPPPAAPTSAARAPPQALRRRGDSRRRQAALFFLNNISLDGR
  PPSLGPGGEKPPPPPAEAREPPAPPPPEPPTGLPARTPAPQGLLSPTQVPTGLGLDGQRQ
  RKRVTSQRCSLEFLEDAVGCAPAQRTKHTSGSPRHKGLKKTHFIKNMRQYDTRNSRIVLI
  CAKRSLCAAFSVLPYGEGLRISDLRVDSQKQRHPSGGVSVSSEMVFELEGVELGADGKVV
  SYAKFLYPTNALVTHKSDSHGLLPTPRPSVPRTLPGSRHKPAPTKSAPASTELGSDVGDT
  LEYNPNLLDDPQWPCGKHKRVLIFASYMTTVIEYVKPSDLKKDMNETFREKFPHVKLTLS
  KIRSLKREMRSLSEECSLEPVTVAMAYVYFEKLVLQGKLSKQNRKLCAGACVLLAAKISS
  DLRKSGVTQLIDKLEERFRFNRRDLIGFEFTVLVALELALYLPENQVLPHYRRLTQQF
• Function: Unknown. Probably involved in G1-S cell cycle transition.
• Reactome Pathway: Factors involved in megakaryocyte development and platelet production (R-HSA-983231)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Genetic Variation	[1]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[1]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]

3 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 CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of CDK5 and ABL1 enzyme substrate 2 (CABLES2).	[14]

References

• [1] Novel Common Genetic Susceptibility Loci for Colorectal Cancer.J Natl Cancer Inst. 2019 Feb 1;111(2):146-157. doi: 10.1093/jnci/djy099.
• [2] In silico pathway analysis and tissue specific cis-eQTL for colorectal cancer GWAS risk variants.BMC Genomics. 2017 May 15;18(1):381. doi: 10.1186/s12864-017-3750-2.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.