Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8TPCP)

• DOT Name: Protein shisa-3 homolog (SHISA3)
• Gene Name: SHISA3
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Nasopharyngeal carcinoma
  Neoplasm
  Small lymphocytic lymphoma
• UniProt ID: SHSA3_HUMAN
• Pfam ID: PF13908
• Sequence:
  MRALLALCLLLGWLRWGPAGAQQSGEYCHGWVDVQGNYHEGFQCPEDFDTLDATICCGSC
  ALRYCCAAADARLEQGGCTNDRRELEHPGITAQPVYVPFLIVGSIFIAFIILGSVVAIYC
  CTCLRPKEPSQQPIRFSLRSYQTETLPMILTSTSPRAPSRQSSTATSSSSTGGSIRRFSF
  ARAEPGCLVPSPPPPYTTSHSIHLAQPSGFLVSPQYFAYPLQQEPPLPGKSCPDFSSS
• Function: Plays an essential role in the maturation of presomitic mesoderm cells by individual attenuation of both FGF and WNT signaling.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[6]

4 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 Protein shisa-3 homolog (SHISA3).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein shisa-3 homolog (SHISA3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein shisa-3 homolog (SHISA3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein shisa-3 homolog (SHISA3).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein shisa-3 homolog (SHISA3).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein shisa-3 homolog (SHISA3).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein shisa-3 homolog (SHISA3).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein shisa-3 homolog (SHISA3).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein shisa-3 homolog (SHISA3).	[12]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Protein shisa-3 homolog (SHISA3).	[13]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Protein shisa-3 homolog (SHISA3).	[14]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Protein shisa-3 homolog (SHISA3).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Protein shisa-3 homolog (SHISA3).	[17]

References

• [1] Shisa3 brakes resistance to EGFR-TKIs in lung adenocarcinoma by suppressing cancer stem cell properties.J Exp Clin Cancer Res. 2019 Dec 4;38(1):481. doi: 10.1186/s13046-019-1486-3.
• [2] DNA Hypermethylation of SHISA3 in Colorectal Cancer: An Independent Predictor of Poor Prognosis.Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1481-9. doi: 10.1245/s10434-015-4593-1. Epub 2015 May 13.
• [3] The Shisa3 knockout mouse exhibits normal bone phenotype.J Bone Miner Metab. 2019 Nov;37(6):967-975. doi: 10.1007/s00774-019-01014-y. Epub 2019 Jun 20.
• [4] Shisa3 is associated with prolonged survival through promoting -catenin degradation in lung cancer.Am J Respir Crit Care Med. 2014 Aug 15;190(4):433-44. doi: 10.1164/rccm.201312-2256OC.
• [5] Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability.Cancer Res. 2019 Feb 15;79(4):747-759. doi: 10.1158/0008-5472.CAN-18-1754. Epub 2018 Dec 20.
• [6] Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide.Leuk Lymphoma. 2018 Feb;59(2):423-433. doi: 10.1080/10428194.2017.1339872. Epub 2017 Jun 22.
• [7] 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.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [14] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [15] 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.
• [16] 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.
• [17] 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.