Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0OUDUT)

• DOT Name: Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A)
• Synonyms: IgG Fc receptor II-a; CDw32; Fc-gamma RII-a; Fc-gamma-RIIa; FcRII-a; CD antigen CD32
• Gene Name: FCGR2A
• UniProt ID: FCG2A_HUMAN
• PDB ID: 1FCG; 1H9V; 3D5O; 3RY4; 3RY5; 3RY6
• Pfam ID: PF13895
• Sequence:
  MTMETQMSQNVCPRNLWLLQPLTVLLLLASADSQAAAPPKAVLKLEPPWINVLQEDSVTL
  TCQGARSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSLSDPVHLTVL
  SEWLVLQTPHLEFQEGETIMLRCHSWKDKPLVKVTFFQNGKSQKFSHLDPTFSIPQANHS
  HSGDYHCTGNIGYTLFSSKPVTITVQVPSMGSSSPMGIIVAVVIATAVAAIVAAVVALIY
  CRKKRISANSTDPVKAAQFEPPGRQMIAIRKRQLEETNNDYETADGGYMTLNPRAPTDDD
  KNIYLTLPPNDHVNSNN
• Function: Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens.
• Tissue Specificity: Found on monocytes, neutrophils and eosinophil platelets.
• KEGG Pathway:
  Phagosome (hsa04145)
  Osteoclast differentiation (hsa04380)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Pathogenic Escherichia coli infection (hsa05130)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Coro.virus disease - COVID-19 (hsa05171)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  Role of phospholipids in phagocytosis (R-HSA-2029485)
  Neutrophil degranulation (R-HSA-6798695)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  FCGR activation (R-HSA-2029481)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cetuximab	DMLNCE0	Approved	Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) increases the response of Cetuximab.	[8]

7 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 Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A).	[7]

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] 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.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] 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.
• [7] 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.
• [8] FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol. 2007 Aug 20;25(24):3712-8. doi: 10.1200/JCO.2006.08.8021.