Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLR3CEC)

• DOT Name: Retinoic acid early transcript 1E (RAET1E)
• Synonyms: Lymphocyte effector toxicity activation ligand; NKG2D ligand 4; N2DL-4; NKG2DL4; RAE-1-like transcript 4; UL16-binding protein 4
• Gene Name: RAET1E
• Related Disease:
  Adenocarcinoma
  Herpes simplex infection
  Neoplasm
  Pneumococcal meningitis
  Epithelial ovarian cancer
  Nasopharyngeal carcinoma
• UniProt ID: RAE1E_HUMAN
• Pfam ID: PF00129
• Sequence:
  MRRISLTSSPVRLLLFLLLLLIALEIMVGGHSLCFNFTIKSLSRPGQPWCEAQVFLNKNL
  FLQYNSDNNMVKPLGLLGKKVYATSTWGELTQTLGEVGRDLRMLLCDIKPQIKTSDPSTL
  QVEMFCQREAERCTGASWQFATNGEKSLLFDAMNMTWTVINHEASKIKETWKKDRGLEKY
  FRKLSKGDCDHWLREFLGHWEAMPEPTVSPVNASDIHWSSSSLPDRWIILGAFILLVLMG
  IVLICVWWQNGEWQAGLWPLRTS
• Function: Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.
• Tissue Specificity: Predominantly expressed in the skin, but also expressed in testis and trachea. Up-regulated in tumor cells of different origins. Expression progressively decreased after treatment of tumor cells with retinoic acid.
• KEGG Pathway: .tural killer cell mediated cytotoxicity (hsa04650)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Pneumococcal meningitis	DISM5U0L	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[3]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retinoic acid early transcript 1E (RAET1E).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Retinoic acid early transcript 1E (RAET1E).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Retinoic acid early transcript 1E (RAET1E).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Retinoic acid early transcript 1E (RAET1E).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Retinoic acid early transcript 1E (RAET1E).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Retinoic acid early transcript 1E (RAET1E).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Retinoic acid early transcript 1E (RAET1E).	[12]

References

• [1] Clinicopathological relevance of tumor expression of NK group 2 member D ligands in resected non-small cell lung cancer.Oncotarget. 2019 Nov 26;10(63):6805-6815. doi: 10.18632/oncotarget.27308. eCollection 2019 Nov 26.
• [2] Publisher Correction: TCR ligands: the quest to solve a 500-million-year-old mystery.Nat Immunol. 2019 Apr;20(4):516. doi: 10.1038/s41590-019-0358-5.
• [3] The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D.Blood. 2009 Jul 9;114(2):310-7. doi: 10.1182/blood-2008-12-196287. Epub 2009 May 12.
• [4] V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.Acta Neuropathol Commun. 2016 May 18;4(1):50. doi: 10.1186/s40478-016-0320-9.
• [5] Decreased expression of the NKG2D ligand ULBP4 may be an indicator of poor prognosis in patients with nasopharyngeal carcinoma.Oncotarget. 2017 Jun 27;8(26):42007-42019. doi: 10.18632/oncotarget.14917.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [8] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] 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.
• [11] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.