Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL0459Z)

• DOT Name: Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1)
• Synonyms: LYVE-1; Cell surface retention sequence-binding protein 1; CRSBP-1; Extracellular link domain-containing protein 1; Hyaluronic acid receptor
• Gene Name: LYVE1
• UniProt ID: LYVE1_HUMAN
• Pfam ID: PF00193
• Sequence:
  MARCFSLVLLLTSIWTTRLLVQGSLRAEELSIQVSCRIMGITLVSKKANQQLNFTEAKEA
  CRLLGLSLAGKDQVETALKASFETCSYGWVGDGFVVISRISPNPKCGKNGVGVLIWKVPV
  SRQFAAYCYNSSDTWTNSCIPEIITTKDPIFNTQTATQTTEFIVSDSTYSVASPYSTIPA
  PTTTPPAPASTSIPRRKKLICVTEVFMETSTMSTETEPFVENKAAFKNEAAGFGGVPTAL
  LVLALLFFGAAAGLGFCYVKRYVKAFPFTNKNQQKEMIETKVVKEEKANDSNPNEESKKT
  DKNPEESKSPSKTTVRCLEAEV
• Function: Ligand-specific transporter trafficking between intracellular organelles (TGN) and the plasma membrane. Plays a role in autocrine regulation of cell growth mediated by growth regulators containing cell surface retention sequence binding (CRS). May act as a hyaluronan (HA) transporter, either mediating its uptake for catabolism within lymphatic endothelial cells themselves, or its transport into the lumen of afferent lymphatic vessels for subsequent re-uptake and degradation in lymph nodes. Binds to pericelluar hyaluronan matrices deposited on the surface of leukocytes and facilitates cell adhesion and migration through lymphatic endothelium.
• Tissue Specificity: Mainly expressed in endothelial cells lining lymphatic vessels.
• Reactome Pathway: Hyaluronan uptake and degradation (R-HSA-2160916)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1).	[2]
Marinol	DM70IK5	Approved	Marinol increases the expression of Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1).	[3]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1).	[4]

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 Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1).	[5]

References

• [1] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [4] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [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.