Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCJD51H)

• DOT Name: Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B)
• Synonyms: IgG Fc receptor II-b; CDw32; Fc-gamma RII-b; Fc-gamma-RIIb; FcRII-b; CD antigen CD32
• Gene Name: FCGR2B
• Related Disease: Systemic lupus erythematosus
• UniProt ID: FCG2B_HUMAN
• PDB ID: 2FCB; 3WJJ; 5OCC
• Pfam ID: PF13895
• Sequence:
  MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWIN
  VLQEDSVTLTCRGTHSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSL
  SDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN
  FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAA
  VVALIYCRKKRISALPGYPECREMGETLPEKPANPTNPDEADKVGAENTITYSLLMHPDA
  LEEPDDQNRI
• Function: Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.
• Tissue Specificity: Is the most broadly distributed Fc-gamma-receptor. Expressed in monocyte, neutrophils, macrophages, basophils, eosinophils, Langerhans cells, B-cells, platelets cells and placenta (endothelial cells). Not detected in natural killer cells.
• KEGG Pathway:
  Phagosome (hsa04145)
  Osteoclast differentiation (hsa04380)
  B cell receptor sig.ling pathway (hsa04662)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Measles (hsa05162)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Systemic lupus erythematosus	DISI1SZ7	No Known	Unknown	[1]

1 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 Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[2]

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-b (FCGR2B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[7]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[8]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B).	[9]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] 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.
• [3] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [4] 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.
• [5] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] 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.
• [8] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [9] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.