Details of Drug Off-Target (DOT)

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

• DOT Name: Lck-interacting transmembrane adapter 1 (LIME1)
• Synonyms: Lck-interacting membrane protein; Lck-interacting molecule
• Gene Name: LIME1
• Related Disease:
  Advanced cancer
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: LIME1_HUMAN
• Pfam ID: PF15332
• Sequence:
  MGLPVSWAPPALWVLGCCALLLSLWALCTACRRPEDAVAPRKRARRQRARLQGSATAAEA
  SLLRRTHLCSLSKSDTRLHELHRGPRSSRALRPASMDLLRPHWLEVSRDITGPQAAPSAF
  PHQELPRALPAAAATAGCAGLEATYSNVGLAALPGVSLAASPVVAEYARVQKRKGTHRSP
  QEPQQGKTEVTPAAQVDVLYSRVCKPKRRDPGPTTDPLDPKGQGAILALAGDLAYQTLPL
  RALDVDSGPLENVYESIRELGDPAGRSSTCGAGTPPASSCPSLGRGWRPLPASLP
• Function: Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. In absence of TCR signaling, may be involved in CD4-mediated inhibition of T-cell activation. Couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilization or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules.
• Tissue Specificity: Expressed in peripheral blood lymphocytes, lymphoid tissues, and liver. Present in T-cells and plasma cells, and in various hematopoietic cell lines (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]

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 Lck-interacting transmembrane adapter 1 (LIME1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[5]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Lck-interacting transmembrane adapter 1 (LIME1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Lck-interacting transmembrane adapter 1 (LIME1).	[11]

References

• [1] Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor-negative breast cancer.Int J Cancer. 2017 Jun 1;140(11):2484-2497. doi: 10.1002/ijc.30680. Epub 2017 Mar 21.
• [2] RNA-Seq analysis of non-small cell lung cancer in female never-smokers reveals candidate cancer-associated long non-coding RNAs.Pathol Res Pract. 2016 Jun;212(6):549-54. doi: 10.1016/j.prp.2016.03.006. Epub 2016 Mar 19.
• [3] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] 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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.