Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GMTML)

• DOT Name: Protein shisa-2 homolog (SHISA2)
• Synonyms: Transmembrane protein 46
• Gene Name: SHISA2
• Related Disease:
  Advanced cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SHSA2_HUMAN
• Pfam ID: PF13908
• Sequence:
  MWGARRSSVSSSWNAASLLQLLLAALLAAGARASGEYCHGWLDAQGVWRIGFQCPERFDG
  GDATICCGSCALRYCCSSAEARLDQGGCDNDRQQGAGEPGRADKDGPDGSAVPIYVPFLI
  VGSVFVAFIILGSLVAACCCRCLRPKQDPQQSRAPGGNRLMETIPMIPSASTSRGSSSRQ
  SSTAASSSSSANSGARAPPTRSQTNCCLPEGTMNNVYVNMPTNFSVLNCQQATQIVPHQG
  QYLHPPYVGYTVQHDSVPMTAVPPFMDGLQPGYRQIQSPFPHTNSEQKMYPAVTV
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]

2 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-2 homolog (SHISA2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein shisa-2 homolog (SHISA2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Protein shisa-2 homolog (SHISA2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein shisa-2 homolog (SHISA2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein shisa-2 homolog (SHISA2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein shisa-2 homolog (SHISA2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein shisa-2 homolog (SHISA2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein shisa-2 homolog (SHISA2).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein shisa-2 homolog (SHISA2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein shisa-2 homolog (SHISA2).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein shisa-2 homolog (SHISA2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein shisa-2 homolog (SHISA2).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein shisa-2 homolog (SHISA2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein shisa-2 homolog (SHISA2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein shisa-2 homolog (SHISA2).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Protein shisa-2 homolog (SHISA2).	[8]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Protein shisa-2 homolog (SHISA2).	[8]
ORG2058	DMH1M6N	Investigative	ORG2058 decreases the expression of Protein shisa-2 homolog (SHISA2).	[16]

References

• [1] SHISA2 enhances the aggressive phenotype in prostate cancer through the regulation of WNT5A expression.Oncol Lett. 2017 Dec;14(6):6650-6658. doi: 10.3892/ol.2017.7099. Epub 2017 Sep 28.
• [2] 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.
• [3] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [4] 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.
• [5] 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.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] 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.
• [8] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [14] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.