Details of Drug Off-Target (DOT)

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

• DOT Name: Ly6/PLAUR domain-containing protein 6B (LYPD6B)
• Gene Name: LYPD6B
• UniProt ID: LPD6B_HUMAN
• PDB ID: 6ZSO
• Pfam ID: PF16975
• Sequence:
  MLYKSSDRPAHKVSMLLLCHALAIAVVQIVIFSESWAFAKNINFYNVRPPLDPTPFPNSF
  KCFTCENAGDNYNCNRWAEDKWCPQNTQYCLTVHHFTSHGRSTSITKKCASRSECHFVGC
  HHSRDSEHTECRSCCEGMICNVELPTNHTNAVFAVMHAQRTSGSSAPTLYLPVLAWVFVL
  PLL
• Function: Likely acts as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro acts on nAChRs in a subtype- and stoichiometry-dependent manner. Modulates specifically alpha-3(3):beta-4(2) nAChRs by enhancing the sensitivity to ACh, decreasing ACh-induced maximal current response and increasing the rate of desensitization to ACh; has no effect on alpha-7 homomeric nAChRs; modulates alpha-3(2):alpha-5:beta-4(2) nAChRs in the context of CHRNA5/alpha-5 variant Asn-398 but not its wild-type sequence. However, according to another report in vitro it can weakly inhibits alpha-7 nAChRs.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ly6/PLAUR domain-containing protein 6B (LYPD6B).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ly6/PLAUR domain-containing protein 6B (LYPD6B).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ly6/PLAUR domain-containing protein 6B (LYPD6B).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ly6/PLAUR domain-containing protein 6B (LYPD6B).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ly6/PLAUR domain-containing protein 6B (LYPD6B).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ly6/PLAUR domain-containing protein 6B (LYPD6B).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] 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.
• [6] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.