Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0O30C7)

• DOT Name: Allergin-1 (MILR1)
• Synonyms: Allergy inhibitory receptor 1; Mast cell antigen 32; MCA-32; Mast cell immunoglobulin-like receptor 1
• Gene Name: MILR1
• Related Disease:
  Alzheimer disease
  Autoimmune disease
  Food allergy
  Systemic lupus erythematosus
• UniProt ID: MILR1_HUMAN
• Pfam ID: PF13895 ; PF17736
• Sequence:
  MWSHLNRLLFWSIFSSVTCRKAVLDCEAMKTNEFPSPCLDSKTKVVMKGQNVSMFCSHKN
  KSLQITYSLFRRKTHLGTQDGKGEPAIFNLSITEAHESGPYKCKAQVTSCSKYSRDFSFT
  IVDPVTSPVLNIMVIQTETDRHITLHCLSVNGSLPINYTFFENHVAISPAISKYDREPAE
  FNLTKKNPGEEEEYRCEAKNRLPNYATYSHPVTMPSTGGDSCPFCLKLLLPGLLLLLVVI
  ILILAFWVLPKYKTRKAMRNNVPRDRGDTAMEVGIYANILEKQAKEESVPEVGSRPCVST
  AQDEAKHSQELQYATPVFQEVAPREQEACDSYKSGYVYSELNF
• Function: Immunoglobulin-like receptor which plays an inhibitory role in degranulation of mast cells. Negatively regulates IgE-mediated mast cell activation and suppresses the type I immediate hypersensitivity reaction.
• Tissue Specificity: Expressed in myeloid cells (dendritic cells, macrophages and neutrophils, weak expression on B-cells but not in T-cells or natural killer cells), peripheral blood basophils and mast cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Food allergy	DISMQ1BP	Strong	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[2]

6 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 Allergin-1 (MILR1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Allergin-1 (MILR1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Allergin-1 (MILR1).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Allergin-1 (MILR1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Allergin-1 (MILR1).	[8]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Allergin-1 (MILR1).	[9]

References

• [1] Three-way interaction model to trace the mechanisms involved in Alzheimer's disease transgenic mice.PLoS One. 2017 Sep 21;12(9):e0184697. doi: 10.1371/journal.pone.0184697. eCollection 2017.
• [2] Allergy inhibitory receptor-1 inhibits autoantibody production via upregulation of apoptotic debris clearance by macrophages.Int J Rheum Dis. 2018 Dec;21(12):2071-2078. doi: 10.1111/1756-185X.13381. Epub 2018 Dec 16.
• [3] Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice.Int Immunol. 2020 Mar 7;32(3):213-219. doi: 10.1093/intimm/dxz075.
• [4] 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.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.