Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZBL9Y)

• DOT Name: High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G)
• Synonyms: Fc receptor gamma-chain; FcRgamma; Fc-epsilon RI-gamma; IgE Fc receptor subunit gamma; FceRI gamma
• Gene Name: FCER1G
• UniProt ID: FCERG_HUMAN
• PDB ID: 7Q5T
• Pfam ID: PF02189 ; PF11628
• Sequence:
  MIPAVVLLLLLLVEQAAALGEPQLCYILDAILFLYGIVLTLLYCRLKIQVRKAAITSYEK
  SDGVYTGLSTRNQETYETLKHEKPPQ
• Function: Adapter protein containing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. As a component of the high-affinity immunoglobulin E (IgE) receptor, mediates allergic inflammatory signaling in mast cells. As a constitutive component of interleukin-3 receptor complex, selectively mediates interleukin 4/IL4 production by basophils, priming T-cells toward effector T-helper 2 subset. Associates with pattern recognition receptors CLEC4D and CLEC4E to form a functional signaling complex in myeloid cells. Binding of mycobacterial trehalose 6,6'-dimycolate (TDM) to this receptor complex leads to phosphorylation of ITAM, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes. May function cooperatively with other activating receptors. Functionally linked to integrin beta-2/ITGB2-mediated neutrophil activation. Also involved in integrin alpha-2/ITGA2-mediated platelet activation.
• KEGG Pathway:
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Platelet activation (hsa04611)
  C-type lectin receptor sig.ling pathway (hsa04625)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Tuberculosis (hsa05152)
  Asthma (hsa05310)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Fc epsilon receptor (FCERI) signaling (R-HSA-2454202)
  Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905)
  FCERI mediated MAPK activation (R-HSA-2871796)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  Dectin-2 family (R-HSA-5621480)
  Neutrophil degranulation (R-HSA-6798695)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  GPVI-mediated activation cascade (R-HSA-114604)

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
Valproate	DMCFE9I	Approved	Valproate decreases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[7]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G).	[2]

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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [9] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.