Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYO8A3P)

• DOT Name: UDP-N-acetylglucosamine transporter TMEM241 (TMEM241)
• Synonyms: Solute carrier family 35 member D4; Transmembrane protein 241
• Gene Name: TMEM241
• Related Disease:
  Acute megakaryoblastic leukemia
  Osteoarthritis
• UniProt ID: TM241_HUMAN
• Sequence:
  MCVRRSLVGLTFCTCYLASYLTNKYVLSVLKFTYPTLFQGWQTLIGGLLLHVSWKLGWVE
  INSSSRSHVLVWLPASVLFVGIIYAGSRALSRLAIPVFLTLHNVAEVIICGYQKCFQKEK
  TSPAKICSALLLLAAAGCLPFNDSQFNPDGYFWAIIHLLCVGAYKILQKSQKPSALSDID
  QQYLNYIFSVVLLAFASHPTGDLFSVLDFPFLYFYRFHGSCCASGFLGFFLMFSTVKLKN
  LLAPGQCAAWIFFAKIITAGLSILLFDAILTSATTGCLLLGALGEALLVFSERKSS
• Function: Golgi-localized UDP-N-acetylglucosamine (UDP-GlcNAc) transporter that transports UDP-N-acetylglucosamine into Golgi lumen. Contributes to lysosomal targeting of NPC2, a key protein required for lysosomal cholesterol exiting, and that utilizes the mannose-6-phosphate (M6P) modification pathway for its lysosomal targeting.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[1]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[2]

6 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 UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[5]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[9]

1 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 affects the methylation of UDP-N-acetylglucosamine transporter TMEM241 (TMEM241).	[8]

References

• [1] Integrated differential transcriptome maps of Acute Megakaryoblastic Leukemia (AMKL) in children with or without Down Syndrome (DS).BMC Med Genomics. 2014 Dec 5;7:63. doi: 10.1186/s12920-014-0063-z.
• [2] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.