Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5B9NNM)

• DOT Name: Ly6/PLAUR domain-containing protein 8 (LYPD8)
• Gene Name: LYPD8
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Arthritis
  Colitis
  Neoplasm
• UniProt ID: LYPD8_HUMAN
• Pfam ID: PF00021
• Sequence:
  MKGILVAGITAVLVAAVESLSCVQCNSWEKSCVNSIASECPSHANTSCISSSASSSLETP
  VRLYQNMFCSAENCSEETHITAFTVHVSAEEHFHFVSQCCQGKECSNTSDALDPPLKNVS
  SNAECPACYESNGTSCHGKPWKCYEEEQCVFLVAELKNDIESKSLVLKGCSNVSNATCQF
  LSGENKTLGGVIFRKFECANVNSLTPTSAPTTSHNVGSKASLYLLALASLLLRGLLP
• Function: Secreted protein specifically required to prevent invasion of Gram-negative bacteria in the inner mucus layer of the colon epithelium, a portion of the large intestine which is free of commensal microbiota. Prevents invasion of flagellated microbiota by binding to the flagellum of bacteria, such as P.mirabilis, thereby inhibiting bacterial motility in the intestinal lumen. Segregation of intestinal bacteria and epithelial cells in the colon is required to preserve intestinal homeostasis.
• Tissue Specificity: Expressed in the large intestine. Preferentially expressed on the epithelial layer exposed to the lumen (at protein level).
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	moderate	Biomarker	[2]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[2]
Arthritis	DIST1YEL	Limited	Biomarker	[3]
Colitis	DISAF7DD	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

1 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 Ly6/PLAUR domain-containing protein 8 (LYPD8).	[5]

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 decreases the methylation of Ly6/PLAUR domain-containing protein 8 (LYPD8).	[6]

References

• [1] Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.Am J Pathol. 2002 Jun;160(6):2169-80. doi: 10.1016/S0002-9440(10)61165-0.
• [2] LYPD8 regulates the proliferation and migration of colorectal cancer cells through inhibiting the secretion of IL? and TNF?"Xu J. Zhang W
• [3] Suppressive effect of secretory phospholipase A2 inhibitory peptide on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts, and its antiarthritic activity in hTNFtg mice.Arthritis Res Ther. 2009;11(5):R138. doi: 10.1186/ar2810. Epub 2009 Sep 18.
• [4] Lypd8 inhibits attachment of pathogenic bacteria to colonic epithelia.Mucosal Immunol. 2020 Jan;13(1):75-85. doi: 10.1038/s41385-019-0219-4. Epub 2019 Oct 28.
• [5] 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.
• [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.