Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ1AARI)

• DOT Name: Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3)
• Synonyms: 45 kDa Sin3-associated polypeptide; Suppressor of defective silencing 3 protein homolog
• Gene Name: SUDS3
• Related Disease:
  Advanced cancer
  Major depressive disorder
  Neoplasm
• UniProt ID: SDS3_HUMAN
• Pfam ID: PF08598
• Sequence:
  MSAAGLLAPAPAQAGAPPAPEYYPEEDEELESAEDDERSCRGRESDEDTEDASETDLAKH
  DEEDYVEMKEQMYQDKLASLKRQLQQLQEGTLQEYQKRMKKLDQQYKERIRNAELFLQLE
  TEQVERNYIKEKKAAVKEFEDKKVELKENLIAELEEKKKMIENEKLTMELTGDSMEVKPI
  MTRKLRRRPNDPVPIPDKRRKPAPAQLNYLLTDEQIMEDLRTLNKLKSPKRPASPSSPEH
  LPATPAESPAQRFEARIEDGKLYYDKRWYHKSQAIYLESKDNQKLSCVISSVGANEIWVR
  KTSDSTKMRIYLGQLQRGLFVIRRRSAA
• Function: Regulatory protein which represses transcription and augments histone deacetylase activity of HDAC1. May have a potential role in tumor suppressor pathways through regulation of apoptosis. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes.
• Tissue Specificity: Expressed in various cancer cell ines.
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  Ub-specific processing proteases (R-HSA-5689880)
  Potential therapeutics for SARS (R-HSA-9679191)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the phosphorylation of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[9]

4 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 Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sin3 histone deacetylase corepressor complex component SDS3 (SUDS3).	[10]

References

• [1] Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity.J Biol Chem. 2011 Mar 25;286(12):10505-14. doi: 10.1074/jbc.M110.162321. Epub 2011 Jan 14.
• [2] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways.Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.