Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOWF0FK)

• DOT Name: Programmed cell death 1 ligand 2 (PDCD1LG2)
• Synonyms: PD-1 ligand 2; PD-L2; PDCD1 ligand 2; Programmed death ligand 2; Butyrophilin B7-DC; B7-DC; CD antigen CD273
• Gene Name: PDCD1LG2
• UniProt ID: PD1L2_HUMAN
• PDB ID: 6UMT
• Pfam ID: PF08205
• Sequence:
  MIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITASLQ
  KVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKYLTLKVK
  ASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEGLYQVTSVL
  RLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTWLLHIFIPFCIIAFIFIATV
  IALRKQLCQKLYSSKDTTKRPVTTTKREVNSAI
• Function: Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle progression and cytokine production.
• Tissue Specificity: Highly expressed in heart, placenta, pancreas, lung and liver and weakly expressed in spleen, lymph nodes and thymus.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: PD-1 signaling (R-HSA-389948)

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
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Programmed cell death 1 ligand 2 (PDCD1LG2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Programmed cell death 1 ligand 2 (PDCD1LG2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Programmed cell death 1 ligand 2 (PDCD1LG2).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Programmed cell death 1 ligand 2 (PDCD1LG2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Programmed cell death 1 ligand 2 (PDCD1LG2).	[5]

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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J Clin Invest. 2011 Aug;121(8):3100-8. doi: 10.1172/JCI43656. Epub 2011 Jul 18.
• [4] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.