Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJCPN1)

• DOT Name: STAGA complex 65 subunit gamma (SUPT7L)
• Synonyms: Adenocarcinoma antigen ART1; SPTF-associated factor 65 gamma; STAF65gamma; Suppressor of Ty 7-like
• Gene Name: SUPT7L
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Primary cutaneous T-cell lymphoma
  Lung adenocarcinoma
• UniProt ID: ST65G_HUMAN
• PDB ID: 7KTR; 7KTS; 8H7G
• Pfam ID: PF07524
• Sequence:
  MNLQRYWGEIPISSSQTNRSSFDLLPREFRLVEVHDPPLHQPSANKPKPPTMLDIPSEPC
  SLTIHTIQLIQHNRRLRNLIATAQAQNQQQTEGVKTEESEPLPSCPGSPPLPDDLLPLDC
  KNPNAPFQIRHSDPESDFYRGKGEPVTELSWHSCRQLLYQAVATILAHAGFDCANESVLE
  TLTDVAHEYCLKFTKLLRFAVDREARLGQTPFPDVMEQVFHEVGIGSVLSLQKFWQHRIK
  DYHSYMLQISKQLSEEYERIVNPEKATEDAKPVKIKEEPVSDITFPVSEELEADLASGDQ
  SLPMGVLGAQSERFPSNLEVEASPQASSAEVNASPLWNLAHVKMEPQESEEGNVSGHGVL
  GSDVFEEPMSGMSEAGIPQSPDDSDSSYGSHSTDSLMGSSPVFNQRCKKRMRKI
• Tissue Specificity: Expressed at high levels in adenocarcinomas and gliomas and low in esophageal cancers and malignant hematological disease. Also expressed at high level in the thymus, low in peripheral blood mononuclear cells, and lowest in the stomach, small intestine, and skeletal muscle.
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Definitive	Biomarker	[1]
Primary cutaneous T-cell lymphoma	DIS35WVW	Definitive	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of STAGA complex 65 subunit gamma (SUPT7L).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of STAGA complex 65 subunit gamma (SUPT7L).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of STAGA complex 65 subunit gamma (SUPT7L).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of STAGA complex 65 subunit gamma (SUPT7L).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of STAGA complex 65 subunit gamma (SUPT7L).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of STAGA complex 65 subunit gamma (SUPT7L).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of STAGA complex 65 subunit gamma (SUPT7L).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of STAGA complex 65 subunit gamma (SUPT7L).	[8]

References

• [1] Oncogenomic analysis identifies novel biomarkers for tumor stage mycosis fungoides.Medicine (Baltimore). 2018 May;97(21):e10871. doi: 10.1097/MD.0000000000010871.
• [2] The transcriptional repression activity of STAF65 is facilitated by promoter tethering and nuclear import of class IIa histone deacetylases.Biochim Biophys Acta. 2014 Jul;1839(7):579-91. doi: 10.1016/j.bbagrm.2014.05.007. Epub 2014 May 19.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.