Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUXXUH8)

• DOT Name: TOM1-like protein 2 (TOM1L2)
• Synonyms: Target of Myb-like protein 2
• Gene Name: TOM1L2
• Related Disease:
  Dementia
  Neoplasm
• UniProt ID: TM1L2_HUMAN
• Pfam ID: PF03127 ; PF00790
• Sequence:
  MEFLLGNPFSTPVGQCLEKATDGSLQSEDWTLNMEICDIINETEEGPKDAIRALKKRLNG
  NRNYREVMLALTVLETCVKNCGHRFHILVANRDFIDSVLVKIISPKNNPPTIVQDKVLAL
  IQAWADAFRSSPDLTGVVHIYEELKRKGVEFPMADLDALSPIHTPQRSVPEVDPAATMPR
  SQSQQRTSAGSYSSPPPAPYSAPQAPALSVTGPITANSEQIARLRSELDVVRGNTKVMSE
  MLTEMVPGQEDSSDLELLQELNRTCRAMQQRIVELISRVSNEEVTEELLHVNDDLNNVFL
  RYERFERYRSGRSVQNASNGVLNEVTEDNLIDLGPGSPAVVSPMVGNTAPPSSLSSQLAG
  LDLGTESVSGTLSSLQQCNPRDGFDMFAQTRGNSLAEQRKTVTYEDPQAVGGLASALDNR
  KQSSEGIPVAQPSVMDDIEVWLRTDLKGDDLEEGVTSEEFDKFLEERAKAAEMVPDLPSP
  PMEAPAPASNPSGRKKPERSEDALFAL
• Function: Acts as a MYO6/Myosin VI adapter protein that targets myosin VI to endocytic structures. May also play a role in recruiting clathrin to endosomes. May regulate growth factor-induced mitogenic signaling.
• Tissue Specificity: Ubiquitously expressed with higher expression in heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dementia	DISXL1WY	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Disputed	Biomarker	[2]

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 TOM1-like protein 2 (TOM1L2).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of TOM1-like protein 2 (TOM1L2).	[13]

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 TOM1-like protein 2 (TOM1L2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of TOM1-like protein 2 (TOM1L2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of TOM1-like protein 2 (TOM1L2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of TOM1-like protein 2 (TOM1L2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of TOM1-like protein 2 (TOM1L2).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of TOM1-like protein 2 (TOM1L2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TOM1-like protein 2 (TOM1L2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of TOM1-like protein 2 (TOM1L2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of TOM1-like protein 2 (TOM1L2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of TOM1-like protein 2 (TOM1L2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of TOM1-like protein 2 (TOM1L2).	[15]

References

• [1] Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk.Hum Mol Genet. 2010 May 15;19(10):2068-78. doi: 10.1093/hmg/ddq079. Epub 2010 Feb 18.
• [2] Tom1l2 hypomorphic mice exhibit increased incidence of infections and tumors and abnormal immunologic response.Mamm Genome. 2008 Apr;19(4):246-62. doi: 10.1007/s00335-008-9100-6. Epub 2008 Mar 15.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [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] 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.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.