Details of Drug Off-Target (DOT)

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

• DOT Name: Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU)
• Synonyms: FAU ubiquitin like and ribosomal protein S30 fusion
• Gene Name: FAU
• Related Disease:
  B-cell neoplasm
  Adenocarcinoma
  Burkitt lymphoma
  Gastric cancer
  Lymphoma
  Malignant soft tissue neoplasm
  Neoplasm
  Osteosarcoma
  Sarcoma
  Small lymphocytic lymphoma
  Stomach cancer
• UniProt ID: RS30_HUMAN
• PDB ID: 2L7R ; 4UG0 ; 4V6X ; 5A2Q ; 5AJ0 ; 5FLX ; 5OA3 ; 5T2C ; 6FEC ; 6G18 ; 6G4S ; 6G4W ; 6G51 ; 6G53 ; 6G5H ; 6G5I ; 6IP5 ; 6IP6 ; 6IP8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6Y0G ; 6Y2L ; 6Y57 ; 6YBW ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZLW ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 6ZMT ; 6ZMW ; 6ZN5 ; 6ZOJ ; 6ZOK ; 6ZON ; 6ZP4 ; 6ZUO ; 6ZV6 ; 6ZVH ; 6ZVJ ; 6ZXD ; 6ZXE ; 6ZXF ; 6ZXG ; 6ZXH ; 7A09 ; 7K5I ; 7QP6 ; 7QP7 ; 7R4X ; 7TQL ; 7WTS ; 7WTT ; 7WTU ; 7WTV ; 7WTW ; 7WTX ; 7WTZ ; 7WU0 ; 7XNX ; 7XNY ; 8BS3 ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF04758 ; PF00240
• Sequence:
  MQLFVRAQELHTFEVTGQETVAQIKAHVASLEGIAPEDQVVLLAGAPLEDEATLGQCGVE
  ALTTLEVAGRMLGGKVHGSLARAGKVRGQTPKVAKQEKKKKKTGRAKRRMQYNRRFVNVV
  PTFGKKKGPNANS
• Function: [Ubiquitin-like protein FUBI]: May have pro-apoptotic activity; [Small ribosomal subunit protein eS30]: Component of the 40S subunit of the ribosome. Contributes to the assembly and function of 40S ribosomal subunits.
• KEGG Pathway:
  Ribosome (hsa03010)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Peptide chain elongation (R-HSA-156902)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Viral mRNA Translation (R-HSA-192823)
  Selenocysteine synthesis (R-HSA-2408557)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  Translation initiation complex formation (R-HSA-72649)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Eukaryotic Translation Termination (R-HSA-72764)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  SARS-CoV-1 modulates host translation machinery (R-HSA-9735869)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Sarcoma	DISZDG3U	Strong	Altered Expression	[4]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]

1 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 Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (FAU).	[15]

References

• [1] Molecular mapping of the chromosome 11 breakpoint of t(11;17)(q13;q21) in a t(11;14)(q13;q32)-positive B non-Hodgkin's lymphoma.Genes Chromosomes Cancer. 1993 Dec;8(4):224-9. doi: 10.1002/gcc.2870080404.
• [2] A new monoclonal antibody which binds to the cytoplasm of large cell lymphomas.Hematol Oncol. 1992 Mar-Apr;10(2):95-104. doi: 10.1002/hon.2900100205.
• [3] Discovery of signature genes in gastric cancer associated with prognosis.Neoplasma. 2016;63(2):239-45. doi: 10.4149/209_150531N303.
• [4] fau cDNA encodes a ubiquitin-like-S30 fusion protein and is expressed as an antisense sequence in the Finkel-Biskis-Reilly murine sarcoma virus.Oncogene. 1993 Sep;8(9):2537-46.
• [5] Exclusion of FAU as the multiple endocrine neoplasia type 1 (MEN1) gene.Hum Mol Genet. 1993 Apr;2(4):349-53. doi: 10.1093/hmg/2.4.349.
• [6] fau and its ubiquitin-like domain (FUBI) transforms human osteogenic sarcoma (HOS) cells to anchorage-independence.Oncogene. 2003 Mar 27;22(12):1817-21. doi: 10.1038/sj.onc.1206283.
• [7] 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.
• [8] 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.
• [9] Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene. 2001 Jan 10;262(1-2):207-14. doi: 10.1016/s0378-1119(00)00530-8.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.