Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCLTC0J)

• DOT Name: Cytoskeleton-associated protein 2 (CKAP2)
• Synonyms: CTCL tumor antigen se20-10; Tumor- and microtubule-associated protein
• Gene Name: CKAP2
• Related Disease:
  Advanced cancer
  Adenocarcinoma
  Adenoma
  B-cell lymphoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Glioma
  Leukemia
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Breast cancer
  Breast carcinoma
  Cervical carcinoma
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: CKAP2_HUMAN
• Pfam ID: PF15297
• Sequence:
  MSTPAVPQDLQLPPSQRAQSAFKEQRRQKLKEHLLRRKTLFAYKQENEMLSSSRDQRVVT
  SEDQVQEGTKVLKLKTKMADKENMKRPAESKNNTVVGKHCIPLKPSNELTNSTVVIDTHK
  PKDSNQTPHLLLTEDDPQSQHMTLSQAFHLKNNSKKKQMTTEKQKQDANMPKKPVLGSYR
  GQIVQSKINSFRKPLQVKDESSAATKKLSATIPKATKPQPVNTSSVTVKSNRSSNMTATT
  KFVSTTSQNTQLVRPPIRSHHSNTRDTVKQGISRTSANVTIRKGPHEKELLQSKTALSSV
  KTSSSQGIIRNKTLSRSIASEVIARPASLSNDKLMEKSEPVDQRRHTAGKAIVDSRSAQP
  KETSEERKARLSEWKAGKGRVLKRPPNSVVTQHEPAGQNEKPVGSFWTTMAEEDEQRLFT
  EKVNNTFSECLNLINEGCPKEDILVTLNDLIKNIPDAKKLVKYWICLALIEPITSPIENI
  IAIYEKAILAGAQPIEEMRHTIVDILTMKSQEKANLGENMEKSCASKEEVKEVSIEDTGV
  DVDPEKLEMESKLHRNLLFQDCEKEQDNKTKDPTHDVKTPNTETRTSCLIKYNVSTTPYL
  QSVKKKVQFDGTNSAFKELKFLTPVRRSRRLQEKTSKLPDMLKDHYPCVSSLEQLTELGR
  ETDAFVCRPNAALCRVYYEADTT
• Function: Possesses microtubule stabilizing properties. Involved in regulating aneuploidy, cell cycling, and cell death in a p53/TP53-dependent manner.
• Tissue Specificity: Abundant in testis, thymus, and in tumor derived cell lines, while barely detectable in liver, prostate, and kidney.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[8]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[8]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[9]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[7]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Cytoskeleton-associated protein 2 (CKAP2) affects the response to substance of Topotecan.	[27]
Vinblastine	DM5TVS3	Approved	Cytoskeleton-associated protein 2 (CKAP2) affects the response to substance of Vinblastine.	[27]

17 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 Cytoskeleton-associated protein 2 (CKAP2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cytoskeleton-associated protein 2 (CKAP2).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[17]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[17]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[18]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[19]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[20]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Cytoskeleton-associated protein 2 (CKAP2).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytoskeleton-associated protein 2 (CKAP2).	[26]

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 affects the methylation of Cytoskeleton-associated protein 2 (CKAP2).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cytoskeleton-associated protein 2 (CKAP2).	[25]

References

• [1] CKAP2 expression is associated with glioma tumor growth and acts as a prognostic factor in highgradeglioma.Oncol Rep. 2018 Oct;40(4):2036-2046. doi: 10.3892/or.2018.6611. Epub 2018 Aug 1.
• [2] Up-regulation of cytoskeletal-associated protein 2 in primary human gastric adenocarcinomas.J Cancer Res Clin Oncol. 2003 Nov;129(11):621-30. doi: 10.1007/s00432-003-0484-0. Epub 2003 Aug 26.
• [3] Identification of a novel cDNA, encoding a cytoskeletal associated protein, differentially expressed in diffuse large B cell lymphomas.Oncogene. 1998 Sep 10;17(10):1245-51. doi: 10.1038/sj.onc.1202048.
• [4] Terminal deoxynucleotidyl transferase-initiated molecule beacons arrayed aptamer probe for sensitive detection of metastatic colorectal cancer cells.Talanta. 2019 Sep 1;202:152-158. doi: 10.1016/j.talanta.2019.04.065. Epub 2019 Apr 28.
• [5] Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer.Oncol Rep. 2017 May;37(5):3084-3092. doi: 10.3892/or.2017.5534. Epub 2017 Mar 27.
• [6] RHOA, SEMA3B, and CKAP2 expression in leukaemia of different types: the results of a pilot experiment.Folia Biol (Praha). 2013;59(5):204-6.
• [7] Silencing of cytoskeleton-associated protein 2 represses cell proliferation and induces cell cycle arrest and cell apoptosis in osteosarcoma cells.Biomed Pharmacother. 2018 Oct;106:1396-1403. doi: 10.1016/j.biopha.2018.07.104. Epub 2018 Jul 23.
• [8] CKAP2 (cytoskeleton-associated protein2) is a new prognostic marker in HER2-negative luminal type breast cancer.PLoS One. 2017 Aug 3;12(8):e0182107. doi: 10.1371/journal.pone.0182107. eCollection 2017.
• [9] Involvement of FAK-ERK2 signaling pathway in CKAP2-induced proliferation and motility in cervical carcinoma cell lines.Sci Rep. 2017 May 18;7(1):2117. doi: 10.1038/s41598-017-01832-y.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] 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.
• [12] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [13] 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.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [17] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [18] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [19] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [20] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [21] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [22] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [23] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [24] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [25] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.