Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4C0SRR)

• DOT Name: IgG receptor FcRn large subunit p51 (FCGRT)
• Synonyms: FcRn; IgG Fc fragment receptor transporter alpha chain; Neonatal Fc receptor
• Gene Name: FCGRT
• UniProt ID: FCGRN_HUMAN
• PDB ID: 1EXU; 3M17; 3M1B; 4K71; 4N0F; 4N0U; 5BJT; 5BXF; 5WHK; 6C97; 6C98; 6C99; 6FGB; 6ILM; 6LA6; 6LA7; 6NHA; 6QIO; 6QIP; 6WNA; 6WOL; 7B5F; 7C9V; 7Q15; 7XXA
• Pfam ID: PF07654 ; PF00129
• Sequence:
  MGVPRPQPWALGLLLFLLPGSLGAESHLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLS
  YNSLRGEAEPCGAWVWENQVSWYWEKETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCE
  LGPDNTSVPTAKFALNGEEFMNFDLKQGTWGGDWPEALAISQRWQQQDKAANKELTFLLF
  SCPHRLREHLERGRGNLEWKEPPSMRLKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGL
  AAGTGQGDFGPNSDGSFHASSSLTVKSGDEHHYCCIVQHAGLAQPLRVELESPAKSSVLV
  VGIVIGVLLLTAAAVGGALLWRRMRSGLPAPWISLRGDDTGVLLPTPGEAQDADLKDVNV
  IPATA
• Function: Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk. IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation. In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin/ALB ; (Microbial infection) Acts as an uncoating receptor for a panel of echoviruses including Echovirus 5, 6, 7, 9, 11, 13, 25 and 29.
• Tissue Specificity: Expressed in full-term placenta, heart, lung, liver, muscle, kidney, pancreas, and both fetal and adult small intestine.

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 increases the methylation of IgG receptor FcRn large subunit p51 (FCGRT).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of IgG receptor FcRn large subunit p51 (FCGRT).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[9]
Selenium	DM25CGV	Approved	Selenium increases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of IgG receptor FcRn large subunit p51 (FCGRT).	[11]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.