Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3SGX8W)

• DOT Name: T-cell surface protein tactile (CD96)
• Synonyms: Cell surface antigen CD96; T cell-activated increased late expression protein; CD antigen CD96
• Gene Name: CD96
• Related Disease: C syndrome
• UniProt ID: TACT_HUMAN
• PDB ID: 6ARQ
• Sequence:
  MEKKWKYCAVYYIIQIHFVKGVWEKTVNTEENVYATLGSDVNLTCQTQTVGFFVQMQWSK
  VTNKIDLIAVYHPQYGFYCAYGRPCESLVTFTETPENGSKWTLHLRNMSCSVSGRYECML
  VLYPEGIQTKIYNLLIQTHVTADEWNSNHTIEIEINQTLEIPCFQNSSSKISSEFTYAWS
  VENSSTDSWVLLSKGIKEDNGTQETLISQNHLISNSTLLKDRVKLGTDYRLHLSPVQIFD
  DGRKFSCHIRVGPNKILRSSTTVKVFAKPEIPVIVENNSTDVLVERRFTCLLKNVFPKAN
  ITWFIDGSFLHDEKEGIYITNEERKGKDGFLELKSVLTRVHSNKPAQSDNLTIWCMALSP
  VPGNKVWNISSEKITFLLGSEISSTDPPLSVTESTLDTQPSPASSVSPARYPATSSVTLV
  DVSALRPNTTPQPSNSSMTTRGFNYPWTSSGTDTKKSVSRIPSETYSSSPSGAGSTLHDN
  VFTSTARAFSEVPTTANGSTKTNHVHITGIVVNKPKDGMSWPVIVAALLFCCMILFGLGV
  RKWCQYQKEIMERPPPFKPPPPPIKYTCIQEPNESDLPYHEMETL
• Function: May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation.
• Tissue Specificity: Expressed on normal T-cell lines and clones, and some transformed T-cells, but no other cultured cell lines tested. It is expressed at very low levels on activated B-cells.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
C syndrome	DISMHGXP	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of T-cell surface protein tactile (CD96).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of T-cell surface protein tactile (CD96).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of T-cell surface protein tactile (CD96).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of T-cell surface protein tactile (CD96).	[4]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of T-cell surface protein tactile (CD96).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of T-cell surface protein tactile (CD96).	[7]

References

• [1] Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome. Am J Hum Genet. 2007 Oct;81(4):835-41. doi: 10.1086/522014. Epub 2007 Aug 27.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
• [5] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [6] 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.
• [7] 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.