Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI7I47T)

• DOT Name: Immunoglobulin mu Fc receptor (FCMR)
• Synonyms: IgM FcR; Fas apoptotic inhibitory molecule 3; FAIM3; Regulator of Fas-induced apoptosis Toso
• Gene Name: FCMR
• Related Disease:
  Colon cancer
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
  Bacterial infection
• UniProt ID: FCMR_HUMAN
• PDB ID: 7YSG; 7YTC; 7YTD; 7YTE; 8BPE; 8BPF; 8BPG
• Pfam ID: PF07686
• Sequence:
  MDFWLWPLYFLPVSGALRILPEVKVEGELGGSVTIKCPLPEMHVRIYLCREMAGSGTCGT
  VVSTTNFIKAEYKGRVTLKQYPRKNLFLVEVTQLTESDSGVYACGAGMNTDRGKTQKVTL
  NVHSEYEPSWEEQPMPETPKWFHLPYLFQMPAYASSSKFVTRVTTPAQRGKVPPVHHSSP
  TTQITHRPRVSRASSVAGDKPRTFLPSTTASKISALEGLLKPQTPSYNHHTRLHRQRALD
  YGSQSGREGQGFHILIPTILGLFLLALLGLVVKRAVERRKALSRRARRLAVRMRALESSQ
  RPRGSPRPRSQNNIYSACPRRARGADAAGTGEAPVPGPGAPLPPAPLQVSESPWLHAPSL
  KTSCEYVSLYHQPAAMMEDSDSDDYINVPA
• Function: High-affinity Fc receptor for immunoglobulin M (IgM), both secreted and membrane-bound IgM. Primarily regulates IgM transport and homeostasis. Primarily regulates IgM transport and homeostasis. In lymphoid cells, enables exocytosis of membrane-bound IgM on the plasma membrane as well as endocytosis of IgM-antigen complexes toward lysosomes for degradation. In mucosal epithelium, mediates retrotranscytosis of antigen-IgM complexes across mucosal M cells toward antigen-presenting cells in mucosal lymphoid tissues. Triggers costimulatory signaling and mediates most of IgM effector functions involved in B cell development and primary immune response to infection. Likely limits tonic IgM BCR signaling to self-antigens for proper negative selection of autoreactive B cells in the bone marrow and for the maintenance of regulatory B cell pool in peripheral lymphoid organs. Mediates antibody responses to T cell-dependent and T cell-independent antigens and promotes induction of an efficient neutralizing IgG response. Engages in cross-talk with antigen-receptor signaling via the non-canonical NF-kappa-B, MAP kinases and calcium signaling pathways.
• Tissue Specificity: Expressed by CD19-positive B cells and CD4-positive and CD8-positive T cell populations in primary and secondary lymphoid tissues (at protein level). Among B cell subsets, detected in a subset of bone marrow pro- and pre-B cells, in most follicular and memory B cells and in a small subset of germinal center B cells (at protein level). Expressed at lower levels in CD56-positive NK cells (at protein level) . Expressed in lymph nodes, lung, thymus and kidneys. Very weak expression detected in spleen, liver, heart, and salivary gland.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[3]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[4]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Immunoglobulin mu Fc receptor (FCMR).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Immunoglobulin mu Fc receptor (FCMR).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[9]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[10]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[11]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Immunoglobulin mu Fc receptor (FCMR).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Immunoglobulin mu Fc receptor (FCMR).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Immunoglobulin mu Fc receptor (FCMR).	[16]
Propanoic Acid	DM9TN2W	Investigative	Propanoic Acid decreases the expression of Immunoglobulin mu Fc receptor (FCMR).	[17]

References

• [1] Gene expression analysis in colorectal cancer using practical DNA array filter.Dis Colon Rectum. 2001 Feb;44(2):295-9. doi: 10.1007/BF02234309.
• [2] Chimeric antigen receptor T cells targeting Fc receptor selectively eliminate CLL cells while sparing healthy B cells.Blood. 2016 Sep 29;128(13):1711-22. doi: 10.1182/blood-2016-01-692046. Epub 2016 Aug 17.
• [3] Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.Mol Immunol. 2006 Mar;43(9):1497-507. doi: 10.1016/j.molimm.2005.07.039. Epub 2005 Sep 6.
• [4] Fc Receptor Promotes the Survival and Activation of Marginal Zone B Cells and Protects Mice against Bacterial Sepsis.Front Immunol. 2018 Feb 5;9:160. doi: 10.3389/fimmu.2018.00160. eCollection 2018.
• [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] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [11] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [12] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [13] 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.
• [14] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [15] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [16] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [17] Propionic acid induces mitochondrial dysfunction and affects gene expression for mitochondria biogenesis and neuronal differentiation in SH-SY5Y cell line. Neurotoxicology. 2019 Dec;75:116-122. doi: 10.1016/j.neuro.2019.09.009. Epub 2019 Sep 14.