Details of Drug Off-Target (DOT)

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

• DOT Name: Teashirt homolog 2 (TSHZ2)
• Synonyms: Ovarian cancer-related protein 10-2; OVC10-2; Zinc finger protein 218
• Gene Name: TSHZ2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Childhood myelodysplastic syndrome
  Myelodysplastic syndrome
  Neoplasm
  Prostate cancer
• UniProt ID: TSH2_HUMAN
• Sequence:
  MPRRKQQAPKRAAGYAQEEQLKEEEEIKEEEEEEDSGSVAQLQGGNDTGTDEELETGPEQ
  KGCFSYQNSPGSHLSNQDAENESLLSDASDQVSDIKSVCGRDASDKKAHTHVRLPNEAHN
  CMDKMTAVYANILSDSYWSGLGLGFKLSNSERRNCDTRNGSNKSDFDWHQDALSKSLQQN
  LPSRSVSKPSLFSSVQLYRQSSKMCGTVFTGASRFRCRQCSAAYDTLVELTVHMNETGHY
  QDDNRKKDKLRPTSYSKPRKRAFQDMDKEDAQKVLKCMFCGDSFDSLQDLSVHMIKTKHY
  QKVPLKEPVPTISSKMVTPAKKRVFDVNRPCSPDSTTGSFADSFSSQKNANLQLSSNNRY
  GYQNGASYTWQFEACKSQILKCMECGSSHDTLQQLTTHMMVTGHFLKVTSSASKKGKQLV
  LDPLAVEKMQSLSEAPNSDSLAPKPSSNSASDCTASTTELKKESKKERPEETSKDEKVVK
  SEDYEDPLQKPLDPTIKYQYLREEDLEDGSKGGGDILKSLENTVTTAINKAQNGAPSWSA
  YPSIHAAYQLSEGTKPPLPMGSQVLQIRPNLTNKLRPIAPKWKVMPLVSMPTHLAPYTQV
  KKESEDKDEAVKECGKESPHEEASSFSHSEGDSFRKSETPPEAKKTELGPLKEEEKLMKE
  GSEKEKPQPLEPTSALSNGCALANHAPALPCINPLSALQSVLNNHLGKATEPLRSPSCSS
  PSSSTISMFHKSNLNVMDKPVLSPASTRSASVSRRYLFENSDQPIDLTKSKSKKAESSQA
  QSCMSPPQKHALSDIADMVKVLPKATTPKPASSSRVPPMKLEMDVRRFEDVSSEVSTLHK
  RKGRQSNWNPQHLLILQAQFASSLFQTSEGKYLLSDLGPQERMQISKFTGLSMTTISHWL
  ANVKYQLRKTGGTKFLKNMDKGHPIFYCSDCASQFRTPSTYISHLESHLGFQMKDMTRLS
  VDQQSKVEQEISRVSSAQRSPETIAAEEDTDSKFKCKLCCRTFVSKHAVKLHLSKTHSKS
  PEHHSQFVTDVDEE
• Function: Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential).
• Tissue Specificity: Expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Genetic Variation	[2]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]

3 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 Teashirt homolog 2 (TSHZ2).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Teashirt homolog 2 (TSHZ2).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Teashirt homolog 2 (TSHZ2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Teashirt homolog 2 (TSHZ2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Teashirt homolog 2 (TSHZ2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Teashirt homolog 2 (TSHZ2).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Teashirt homolog 2 (TSHZ2).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Teashirt homolog 2 (TSHZ2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Teashirt homolog 2 (TSHZ2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Teashirt homolog 2 (TSHZ2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Teashirt homolog 2 (TSHZ2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Teashirt homolog 2 (TSHZ2).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Teashirt homolog 2 (TSHZ2).	[16]
Manganese	DMKT129	Investigative	Manganese increases the expression of Teashirt homolog 2 (TSHZ2).	[17]

References

• [1] Master Regulators of Signaling Pathways: An Application to the Analysis of Gene Regulation in Breast Cancer.Front Genet. 2019 Dec 3;10:1180. doi: 10.3389/fgene.2019.01180. eCollection 2019.
• [2] ASXL1 gene alterations in patients with isolated 20q deletion.Neoplasma. 2019 Jul 23;66(4):627-630. doi: 10.4149/neo_2018_181010N754.
• [3] Rare and frequent promoter methylation, respectively, of TSHZ2 and 3 genes that are both downregulated in expression in breast and prostate cancers.PLoS One. 2011 Mar 14;6(3):e17149. doi: 10.1371/journal.pone.0017149.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [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] 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] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.