Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOBCS2O)

• DOT Name: High affinity immunoglobulin gamma Fc receptor I (FCGR1A)
• Synonyms: IgG Fc receptor I; Fc-gamma RI; FcRI; Fc-gamma RIA; FcgammaRIa; CD antigen CD64
• Gene Name: FCGR1A
• UniProt ID: FCGR1_HUMAN
• PDB ID: 3RJD; 4W4O; 4X4M; 4ZNE; 8DIN; 8DIR; 8DJ7
• Pfam ID: PF00047 ; PF13895 ; PF13927
• Sequence:
  MWFLTTLLLWVPVDGQVDTTKAVITLQPPWVSVFQEETVTLHCEVLHLPGSSSTQWFLNG
  TATQTSTPSYRITSASVNDSGEYRCQRGLSGRSDPIQLEIHRGWLLLQVSSRVFTEGEPL
  ALRCHAWKDKLVYNVLYYRNGKAFKFFHWNSNLTILKTNISHNGTYHCSGMGKHRYTSAG
  ISVTVKELFPAPVLNASVTSPLLEGNLVTLSCETKLLLQRPGLQLYFSFYMGSKTLRGRN
  TSSEYQILTARREDSGLYWCEAATEDGNVLKRSPELELQVLGLQLPTPVWFHVLFYLAVG
  IMFLVNTVLWVTIRKELKRKKKWDLEISLDSGHEKKVISSLQEDRHLEEELKCQEQKEEQ
  LQEGVHRKEPQGAT
• Function: High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses. Mediates IgG effector functions on monocytes triggering antibody-dependent cellular cytotoxicity (ADCC) of virus-infected cells.
• Tissue Specificity: Monocyte/macrophage specific.
• KEGG Pathway:
  Phagosome (hsa04145)
  Osteoclast differentiation (hsa04380)
  Neutrophil extracellular trap formation (hsa04613)
  Hematopoietic cell lineage (hsa04640)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Leishmaniasis (hsa05140)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  FCGR activation (R-HSA-2029481)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  Role of phospholipids in phagocytosis (R-HSA-2029485)
  Interferon gamma signaling (R-HSA-877300)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  Cross-presentation of soluble exogenous antigens (endosomes) (R-HSA-1236978)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[7]

10 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 High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[4]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[5]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[6]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[8]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[9]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[4]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[4]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of High affinity immunoglobulin gamma Fc receptor I (FCGR1A).	[10]

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] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15;17) translocation. Int J Hematol. 2015 Jul;102(1):12-24. doi: 10.1007/s12185-015-1776-2. Epub 2015 Mar 11.
• [5] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [6] 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.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
• [9] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [10] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.