Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOS044E)

• DOT Name: T-cell differentiation antigen CD6 (CD6)
• Synonyms: T12; TP120; CD antigen CD6
• Gene Name: CD6
• UniProt ID: CD6_HUMAN
• PDB ID: 5A2E
• Pfam ID: PF00530
• Sequence:
  MWLFFGITGLLTAALSGHPSPAPPDQLNTSSAESELWEPGERLPVRLTNGSSSCSGTVEV
  RLEASWEPACGALWDSRAAEAVCRALGCGGAEAASQLAPPTPELPPPPAAGNTSVAANAT
  LAGAPALLCSGAEWRLCEVVEHACRSDGRRARVTCAENRALRLVDGGGACAGRVEMLEHG
  EWGSVCDDTWDLEDAHVVCRQLGCGWAVQALPGLHFTPGRGPIHRDQVNCSGAEAYLWDC
  PGLPGQHYCGHKEDAGAVCSEHQSWRLTGGADRCEGQVEVHFRGVWNTVCDSEWYPSEAK
  VLCQSLGCGTAVERPKGLPHSLSGRMYYSCNGEELTLSNCSWRFNNSNLCSQSLAARVLC
  SASRSLHNLSTPEVPASVQTVTIESSVTVKIENKESRELMLLIPSIVLGILLLGSLIFIA
  FILLRIKGKYALPVMVNHQHLPTTIPAGSNSYQPVPITIPKEVFMLPIQVQAPPPEDSDS
  GSDSDYEHYDFSAQPPVALTTFYNSQRHRVTDEEVQQSRFQMPPLEEGLEELHASHIPTA
  NPGHCITDPPSLGPQYHPRSNSESSTSSGEDYCNSPKSKLPPWNPQVFSSERSSFLEQPP
  NLELAGTQPAFSAGPPADDSSSTSSGEWYQNFQPPPQPPSEEQFGCPGSPSPQPDSTDND
  DYDDISAA
• Function: Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166. Contributes to signaling cascades triggered by activation of the TCR/CD3 complex. Functions as a costimulatory molecule; promotes T-cell activation and proliferation. Contributes to the formation and maturation of the immunological synapse. Functions as a calcium-dependent pattern receptor that binds and aggregates both Gram-positive and Gram-negative bacteria. Binds both lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteichoic acid from Gram-positive bacteria. LPS binding leads to the activation of signaling cascades and down-stream MAP kinases. Mediates activation of the inflammatory response and the secretion of pro-inflammatory cytokines in response to LPS.
• Tissue Specificity: Detected on thymocytes . Detected on peripheral blood T-cells . Detected on natural killer (NK) cells . Soluble CD6 is detected in blood serum (at protein level) . Detected in spleen, thymus, appendix, lymph node and peripheral blood leukocytes . Expressed by thymocytes, mature T-cells, a subset of B-cells known as B-1 cells, and by some cells in the brain.
• KEGG Pathway: Cell adhesion molecules (hsa04514)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of T-cell differentiation antigen CD6 (CD6).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of T-cell differentiation antigen CD6 (CD6).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of T-cell differentiation antigen CD6 (CD6).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Aspirin decreases the expression of T-cell differentiation antigen CD6 (CD6).	[3]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [3] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [4] 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.