Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOK3301)

• DOT Name: P-selectin glycoprotein ligand 1 (SELPLG)
• Synonyms: PSGL-1; Selectin P ligand; CD antigen CD162
• Gene Name: SELPLG
• UniProt ID: SELPL_HUMAN
• PDB ID: 1G1S
• Sequence:
  MPLQLLLLLILLGPGNSLQLWDTWADEAEKALGPLLARDRRQATEYEYLDYDFLPETEPP
  EMLRNSTDTTPLTGPGTPESTTVEPAARRSTGLDAGGAVTELTTELANMGNLSTDSAAME
  IQTTQPAATEAQTTQPVPTEAQTTPLAATEAQTTRLTATEAQTTPLAATEAQTTPPAATE
  AQTTQPTGLEAQTTAPAAMEAQTTAPAAMEAQTTPPAAMEAQTTQTTAMEAQTTAPEATE
  AQTTQPTATEAQTTPLAAMEALSTEPSATEALSMEPTTKRGLFIPFSVSSVTHKGIPMAA
  SNLSVNYPVGAPDHISVKQCLLAILILALVATIFFVCTVVLAVRLSRKGHMYPVRNYSPT
  EMVCISSLLPDGGEGPSATANGGLSKAKSPGLTPEPREDREGDDLTLHSFLP
• Function: A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial steps in inflammation. Critical for the initial leukocyte capture; (Microbial infection) Acts as a receptor for enterovirus 71.
• Tissue Specificity: Expressed on neutrophils, monocytes and most lymphocytes.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Neutrophil extracellular trap formation (hsa04613)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[6]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[10]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of P-selectin glycoprotein ligand 1 (SELPLG).	[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 P-selectin glycoprotein ligand 1 (SELPLG).	[8]

References

• [1] 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.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [6] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.