Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL4QUZX)

• DOT Name: Transmembrane protein PVRIG (PVRIG)
• Synonyms: CD112 receptor; CD112R; Poliovirus receptor-related immunoglobulin domain-containing protein
• Gene Name: PVRIG
• UniProt ID: PVRIG_HUMAN
• Sequence:
  MRTEAQVPALQPPEPGLEGAMGHRTLVLPWVLLTLCVTAGTPEVWVQVRMEATELSSFTI
  RCGFLGSGSISLVTVSWGGPNGAGGTTLAVLHPERGIRQWAPARQARWETQSSISLILEG
  SGASSPCANTTFCCKFASFPEGSWEACGSLPPSSDPGLSAPPTPAPILRADLAGILGVSG
  VLLFGCVYLLHLLRRHKHRPAPRLQPSRTSPQAPRARAWAPSQASQAALHVPYATINTSC
  RPATLDTAHPHGGPSWWASLPTHAAHRPQGPAAWASTPIPARGSFVSVENGLYAQAGERP
  PHTGPGLTLFPDPRGPRAMEGPLGVR
• Function: Cell surface receptor for NECTIN2. May act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals. Following interaction with NECTIN2, inhibits T-cell proliferation. Competes with CD226 for NECTIN2-binding.
• Tissue Specificity: Expressed in some types of immune cells. Expressed at low levels on the surface of freshly isolated T-cells and natural killer (NK) cells, predominantly on CD8+ T-cells (mainly memory/effector, but not naive cells) and on both CD16+ and CD16- NK cells. T-cell expression levels are variable among individuals. Not detected in B-cells, naive or helper T-cells, monocytes, nor neutrophils (at protein level). Not detected in dendritic cells.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transmembrane protein PVRIG (PVRIG).	[1]

8 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 Transmembrane protein PVRIG (PVRIG).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein PVRIG (PVRIG).	[3]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transmembrane protein PVRIG (PVRIG).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein PVRIG (PVRIG).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein PVRIG (PVRIG).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein PVRIG (PVRIG).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane protein PVRIG (PVRIG).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transmembrane protein PVRIG (PVRIG).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.