Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZY9E9)

• DOT Name: Doublesex- and mab-3-related transcription factor A1 (DMRTA1)
• Gene Name: DMRTA1
• Related Disease:
  Oral mucositis
  Bladder cancer
  Cataract
  Non-insulin dependent diabetes
  Obesity
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Influenza
• UniProt ID: DMRTA_HUMAN
• Pfam ID: PF00751 ; PF03474 ; PF20624
• Sequence:
  MERSQCGSRDRGVSGRPHLAPGLVVAAPPPPSPALPVPSGMQVPPAFLRPPSLFLRAAAA
  AAAAAAATSGSGGCPPAPGLESGVGAVGCGYPRTPKCARCRNHGVVSALKGHKRFCRWRD
  CACAKCTLIAERQRVMAAQVALRRQQAQEESEARGLQRLLCSGLSWPPGGRASGGGGRAE
  NPQSTGGPAAGAALGLGALRQASGSATPAFEVFQQDYPEEKQEQKESKCESCQNGQEELI
  SKSHQLYLGSSSRSNGVIGKQSIGSSISEYSNKPDSILSPHPGEQSGGEESPRSLSSSDL
  ESGNESEWVKDLTATKASLPTVSSRPRDPLDILTKIFPNYRRSRLEGILRFCKGDVVQAI
  EQVLNGKEHKPDNRNLANSEELENTAFQRASSFSLAGIGFGTLGNKSAFSPLQTTSASYG
  GDSSLYGVNPRVGISPLRLAYSSAGRGLSGFMSPYLTPGLVPTLPFRPALDYAFSGMIRD
  SSYLSSKDSITCGRLYFRPNQDNP
• Tissue Specificity: Expressed in liver, kidney, pancreas, prostate and weakly detected in testis and ovary.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral mucositis	DISS93V5	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[2]
Cataract	DISUD7SL	Strong	Altered Expression	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Genetic Variation	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[3]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[2]
Influenza	DIS3PNU3	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[11]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[12]

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 decreases the methylation of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Doublesex- and mab-3-related transcription factor A1 (DMRTA1).	[9]

References

• [1] GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis.Support Care Cancer. 2015 Mar;23(3):841-9. doi: 10.1007/s00520-014-2406-x. Epub 2014 Sep 14.
• [2] Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.Oncogene. 2017 Jan 5;36(1):35-46. doi: 10.1038/onc.2016.172. Epub 2016 Jun 6.
• [3] Risk factors for diabetic macular oedema in type 2 diabetes: A case-control study in a United Kingdom primary care setting.Prim Care Diabetes. 2017 Jun;11(3):288-296. doi: 10.1016/j.pcd.2017.03.002. Epub 2017 Apr 7.
• [4] DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response.Virol J. 2019 Feb 20;16(1):21. doi: 10.1186/s12985-019-1125-9.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.