Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKYMT99)

• DOT Name: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR)
• Synonyms: Calcium-binding protein 86; Cancer/testis antigen 88; CT88; Fibrousheathin II; Fibrousheathin-2; FSP-2; Testis-specific calcium-binding protein CBP86
• Gene Name: CABYR
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Testicular cancer
  Brain neoplasm
  Lung cancer
  Lung carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
• UniProt ID: CABYR_HUMAN
• Pfam ID: PF02197
• Sequence:
  MISSKPRLVVPYGLKTLLEGISRAVLKTNPSNINQFAAAYFQELTMYRGNTTMDIKDLVK
  QFHQIKVEKWSEGTTPQKKLECLKEPGKTSVESKVPTQMEKSTDTDEDNVTRTEYSDKTT
  QFPSVYAVPGTEQTEAVGGLSSKPATPKTTTPPSSPPPTAVSPEFAYVPADPAQLAAQML
  GKVSSIHSDQSDVLMVDVATSMPVVIKEVPSSEAAEDVMVAAPLVCSGKVLEVQVVNQTS
  VHVDLGSQPKENEAEPSTASSVPLQDEQEPPAYDQAPEVTLQADIEVMSTVHISSVYNDV
  PVTEGVVYIEQLPEQIVIPFTDQVACLKENEQSKENEQSPRVSPKSVVEKTTSGMSKKSV
  ESVKLAQLEENAKYSSVYMEAEATALLSDTSLKGQPEVPAQLLDAEGAIKIGSEKSLHLE
  VEITSIVSDNTGQEESGENSVPQEMEGKPVLSGEAAEAVHSGTSVKSSSGPFPPAPEGLT
  APEIEPEGESTAE
• Function: May function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction. Isoform 1 binds calcium in vitro. Isoform 2 and isoform 6 probably bind calcium. Isoform 3 and isoform 5 do not bind calcium in vitro. Isoform 4 probably does not bind calcium.
• Tissue Specificity: Expressed in elongating spermatids and spermatozoa (at protein level). Isoform 1 is expressed in testis. Isoform 3 and isoform 5 are also expressed in brain, pancreas and numerous brain tumors.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[2]
Brain neoplasm	DISY3EKS	moderate	Biomarker	[2]
Lung cancer	DISCM4YA	moderate	Biomarker	[3]
Lung carcinoma	DISTR26C	moderate	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Disputed	Biomarker	[4]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) affects the response to substance of Fluorouracil.	[15]
Topotecan	DMP6G8T	Approved	Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) affects the response to substance of Topotecan.	[15]

2 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 Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[13]

8 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 Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Calcium-binding tyrosine phosphorylation-regulated protein (CABYR).	[14]

References

• [1] Upregulated calcium-binding tyrosine phosphorylation-regulated protein-a/b regulates cell proliferation and apoptosis and predicts poor prognosis in hepatocellular carcinoma.J Cell Biochem. 2020 Apr;121(4):2938-2949. doi: 10.1002/jcb.29538. Epub 2019 Nov 6.
• [2] CABYR is a novel cancer-testis antigen in lung cancer.Clin Cancer Res. 2007 Feb 15;13(4):1288-97. doi: 10.1158/1078-0432.CCR-06-1742.
• [3] Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation.Oncotarget. 2016 Feb 23;7(8):9513-24. doi: 10.18632/oncotarget.7069.
• [4] Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.PLoS Genet. 2007 Sep;3(9):1709-23. doi: 10.1371/journal.pgen.0030157. Epub 2007 Jul 31.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [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] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [13] 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.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] 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.