Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2W20Y)

• DOT Name: LINE-1 type transposase domain-containing protein 1 (L1TD1)
• Synonyms: ES cell-associated protein 11
• Gene Name: L1TD1
• Related Disease:
  Advanced cancer
  Brain neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Lung cancer
  Medulloblastoma
  Neoplasm
  Non-small-cell lung cancer
  Gastritis
  Myeloproliferative neoplasm
• UniProt ID: LITD1_HUMAN
• PDB ID: 2LR6; 3SOO
• Pfam ID: PF17490 ; PF02994
• Sequence:
  MSDVSTSVQSKFARLAKKKENITYMKREQLTETDKDIAPVLDLKCKDVSAIMNKFKVLME
  IQDLMFEEMRETLKNDLKAVLGGKATIPEVKNSENSSSRTEFQQIINLALQKTGMVGKIE
  GENSKIGDDNENLTFKLEVNELSGKLDNTNEYNSNDGKKLPQGESRSYEVMGSMEETLCN
  IDDRDGNRNVHLEFTERESRKDGEDEFVKEMREERKFQKLKNKEEVLKASREEKVLMDEG
  AVLTLVADLSSATLDISKQWSNVFNILRENDFEPKFLCEVKLAFKCDGEIKTFSDLQSLR
  KFASQKSSVKELLKDVLPQKEEINQGGRKYGIQEKRDKTLIDSKHRAGEITSDGLSFLFL
  KEVKVAKPEEMKNLETQEEEFSELEELDEEASGMEDDEDTSGLEEEEEEPSGLEEEEEEE
  ASGLEEDEASGLEEEEEQTSEQDSTFQGHTLVDAKHEVEITSDGMETTFIDSVEDSESEE
  EEEGKSSETGKVKTTSLTEKKASRRQKEIPFSYLVGDSGKKKLVKHQVVHKTQEEEETAV
  PTSQGTGTPCLTLCLASPSKSLEMSHDEHKKHSHTNLSISTGVTKLKKTEEKKHRTLHTE
  ELTSKEADLTEETEENLRSSVINSIREIKEEIGNLKSSHSGVLEIENSVDDLSSRMDILE
  ERIDSLEDQIEEFSKDTMQMTKQIISKERQRDIEERSRSCNIRLIGIPEKESYENRAEDI
  IKEIIDENFAELKKGSSLEIVSACRVPSKIDEKRLTPRHILVKFWNSSDKEKIIRASRER
  REITYQGTRIRLTADLSLDTLDARSKWSNVFKVLLEKGFNPRILYPAKMAFDFRGKTKVF
  LSIEEFRDYVLHMPTLRELLGNNIP

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Genetic Variation	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[3]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[3]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[3]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[5]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Gastritis	DIS8G07K	moderate	Posttranslational Modification	[6]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[16]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of LINE-1 type transposase domain-containing protein 1 (L1TD1).	[14]

References

• [1] RNA-binding protein L1TD1 interacts with LIN28 via RNA and is required for human embryonic stem cell self-renewal and cancer cell proliferation.Stem Cells. 2012 Mar;30(3):452-60. doi: 10.1002/stem.1013.
• [2] Embryonic Stem Cell-Related Protein L1TD1 Is Required for Cell Viability, Neurosphere Formation, and Chemoresistance in Medulloblastoma.Stem Cells Dev. 2015 Nov 15;24(22):2700-8. doi: 10.1089/scd.2015.0052. Epub 2015 Aug 10.
• [3] Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology. 2019 Apr;156(5):1455-1466. doi: 10.1053/j.gastro.2018.11.066. Epub 2018 Dec 6.
• [4] L1TD1 - a prognostic marker for colon cancer.BMC Cancer. 2019 Jul 23;19(1):727. doi: 10.1186/s12885-019-5952-2.
• [5] SPAG6 and L1TD1 are transcriptionally regulated by DNA methylation in non-small cell lung cancers.Mol Cancer. 2017 Jan 5;16(1):1. doi: 10.1186/s12943-016-0568-5.
• [6] LINE-1 hypomethylation is associated with increased CpG island methylation in Helicobacter pylori-related enlarged-fold gastritis.Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2555-64. doi: 10.1158/1055-9965.EPI-08-0112.
• [7] JAK2V617F influences epigenomic changes in myeloproliferative neoplasms.Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):470-476. doi: 10.1016/j.bbrc.2017.10.108. Epub 2017 Oct 21.
• [8] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] LINE-1 methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors. Epigenetics. 2009 Apr 1;4(3):176-84. doi: 10.4161/epi.4.3.8694. Epub 2009 Apr 6.
• [14] 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.
• [15] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [16] 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.