Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT97UIXC)

• DOT Name: Tumor susceptibility gene 101 protein (TSG101)
• Synonyms: ESCRT-I complex subunit TSG101
• Gene Name: TSG101
• UniProt ID: TS101_HUMAN
• PDB ID: 1KPP; 1KPQ; 1M4P; 1M4Q; 1S1Q; 2F0R; 3IV1; 3OBQ; 3OBS; 3OBU; 3OBX; 3P9G; 3P9H; 4EJE; 4YC1; 4ZNY; 5VKG; 6UD0; 6VME; 7NLC; 7ZLX
• Pfam ID: PF05743 ; PF09454
• Sequence:
  MAVSESQLKKMVSKYKYRDLTVRETVNVITLYKDLKPVLDSYVFNDGSSRELMNLTGTIP
  VPYRGNTYNIPICLWLLDTYPYNPPICFVKPTSSMTIKTGKHVDANGKIYLPYLHEWKHP
  QSDLLGLIQVMIVVFGDEPPVFSRPISASYPPYQATGPPNTSYMPGMPGGISPYPSGYPP
  NPSGYPGCPYPPGGPYPATTSSQYPSQPPVTTVGPSRDGTISEDTIRASLISAVSDKLRW
  RMKEEMDRAQAELNALKRTEEDLKKGHQKLEEMVTRLDQEVAEVDKNIELLKKKDEELSS
  ALEKMENQSENNDIDEVIIPTAPLYKQILNLYAEENAIEDTIFYLGEALRRGVIDLDVFL
  KHVRLLSRKQFQLRALMQKARKTAGLSDLY
• Function: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan. It may also play a role in the extracellular release of microvesicles that differ from the exosomes.
• Tissue Specificity: Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas.
• KEGG Pathway:
  Viral life cycle - HIV-1 (hsa03250)
  Endocytosis (hsa04144)
• Reactome Pathway:
  Membrane binding and targetting of GAG proteins (R-HSA-174490)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  HCMV Late Events (R-HSA-9610379)
  Late endosomal microautophagy (R-HSA-9615710)
  Budding and maturation of HIV virion (R-HSA-162588)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Tumor susceptibility gene 101 protein (TSG101) decreases the response to substance of Camptothecin.	[8]

6 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 Tumor susceptibility gene 101 protein (TSG101).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tumor susceptibility gene 101 protein (TSG101).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor susceptibility gene 101 protein (TSG101).	[3]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor susceptibility gene 101 protein (TSG101).	[5]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Tumor susceptibility gene 101 protein (TSG101).	[6]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Tumor susceptibility gene 101 protein (TSG101).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Tumor susceptibility gene 101 protein (TSG101).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tumor susceptibility gene 101 protein (TSG101).	[4]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Resveratrol-induced gene expression profiles in human prostate cancer cells. Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):596-604. doi: 10.1158/1055-9965.EPI-04-0398.
• [6] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [7] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [8] ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.