Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNK3VC)

• DOT Name: Immunoglobulin-like domain-containing receptor 2 (ILDR2)
• Synonyms: Angulin-3
• Gene Name: ILDR2
• UniProt ID: ILDR2_HUMAN
• Pfam ID: PF05624
• Sequence:
  MDRVLLRWISLFWLTAMVEGLQVTVPDKKKVAMLFQPTVLRCHFSTSSHQPAVVQWKFKS
  YCQDRMGESLGMSSTRAQSLSKRNLEWDPYLDCLDSRRTVRVVASKQGSTVTLGDFYRGR
  EITIVHDADLQIGKLMWGDSGLYYCIITTPDDLEGKNEDSVELLVLGRTGLLADLLPSFA
  VEIMPEWVFVGLVLLGVFLFFVLVGICWCQCCPHSCCCYVRCPCCPDSCCCPQALYEAGK
  AAKAGYPPSVSGVPGPYSIPSVPLGGAPSSGMLMDKPHPPPLAPSDSTGGSHSVRKGYRI
  QADKERDSMKVLYYVEKELAQFDPARRMRGRYNNTISELSSLHEEDSNFRQSFHQMRSKQ
  FPVSGDLESNPDYWSGVMGGSSGASRGPSAMEYNKEDRESFRHSQPRSKSEMLSRKNFAT
  GVPAVSMDELAAFADSYGQRPRRADGNSHEARGGSRFERSESRAHSGFYQDDSLEEYYGQ
  RSRSREPLTDADRGWAFSPARRRPAEDAHLPRLVSRTPGTAPKYDHSYLGSARERQARPE
  GASRGGSLETPSKRSAQLGPRSASYYAWSPPGTYKAGSSQDDQEDASDDALPPYSELELT
  RGPSYRGRDLPYHSNSEKKRKKEPAKKTNDFPTRMSLVV
• Function: May be involved in ER stress pathways with effects on lipid homeostasis and insulin secretion. With ILDR1 and LSR, involved in the maintain of the epithelial barrier function through the recruitment of MARVELD2/tricellulin to tricellular tight junctions. Also functions as a B7-like protein family member expressed on immune cells and inflamed tissue and with T-cell inhibitory activity. In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1.
• Tissue Specificity: Expressed in testis, brain, pituitary, colon, heart, nerves, prostate, esophagus, lung liver and small intestine . Highly expressed in macrophages, also expressed in monocytes and at low levels in NK and NKT cells (at protein level) .

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 Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Immunoglobulin-like domain-containing receptor 2 (ILDR2).	[6]

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] 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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.