Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1PKGDI)

• DOT Name: T-lymphocyte surface antigen Ly-9 (LY9)
• Synonyms: Cell surface molecule Ly-9; Lymphocyte antigen 9; SLAM family member 3; SLAMF3; Signaling lymphocytic activation molecule 3; CD antigen CD229
• Gene Name: LY9
• UniProt ID: LY9_HUMAN
• Sequence:
  MVAPKSHTDDWAPGPFSSKPQRSQLQIFSSVLQTSLLFLLMGLRASGKDSAPTVVSGILG
  GSVTLPLNISVDTEIENVIWIGPKNALAFARPKENVTIMVKSYLGRLDITKWSYSLCISN
  LTLNDAGSYKAQINQRNFEVTTEEEFTLFVYEQLQEPQVTMKSVKVSENFSCNITLMCSV
  KGAEKSVLYSWTPREPHASESNGGSILTVSRTPCDPDLPYICTAQNPVSQRSSLPVHVGQ
  FCTDPGASRGGTTGETVVGVLGEPVTLPLALPACRDTEKVVWLFNTSIISKEREEAATAD
  PLIKSRDPYKNRVWVSSQDCSLKISQLKIEDAGPYHAYVCSEASSVTSMTHVTLLIYRRL
  RKPKITWSLRHSEDGICRISLTCSVEDGGNTVMYTWTPLQKEAVVSQGESHLNVSWRSSE
  NHPNLTCTASNPVSRSSHQFLSENICSGPERNTKLWIGLFLMVCLLCVGIFSWCIWKRKG
  RCSVPAFCSSQAEAPADTPEPTAGHTLYSVLSQGYEKLDTPLRPARQQPTPTSDSSSDSN
  LTTEEDEDRPEVHKPISGRYEVFDQVTQEGAGHDPAPEGQADYDPVTPYVTEVESVVGEN
  TMYAQVFNLQGKTPVSQKEESSATIYCSIRKPQVVPPPQQNDLEIPESPTYENFT
• Function: Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. May participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction. Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A. Promotes recruitment of RORC to the IL-17 promoter. May be involved in the maintenance of peripheral cell tolerance by serving as a negative regulator of the immune response. May disable autoantibody responses and inhibit IFN-gamma secretion by CD4(+) T-cells. May negatively regulate the size of thymic innate CD8(+) T-cells and the development of invariant natural killer T (iNKT) cells.
• Tissue Specificity: Increased surface expression on T-cells of systemic lupus erythematosus (SLE) patients.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of T-lymphocyte surface antigen Ly-9 (LY9).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of T-lymphocyte surface antigen Ly-9 (LY9).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of T-lymphocyte surface antigen Ly-9 (LY9).	[2]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of T-lymphocyte surface antigen Ly-9 (LY9).	[3]
Aspirin	DM672AH	Approved	Aspirin increases the expression of T-lymphocyte surface antigen Ly-9 (LY9).	[4]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of T-lymphocyte surface antigen Ly-9 (LY9).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of T-lymphocyte surface antigen Ly-9 (LY9).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of T-lymphocyte surface antigen Ly-9 (LY9).	[8]

References

• [1] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [2] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [3] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [4] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [5] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] 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.