Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI15CY4)

• DOT Name: Histone deacetylase complex subunit SAP30L (SAP30L)
• Synonyms: HCV non-structural protein 4A-transactivated protein 2; Sin3 corepressor complex subunit SAP30L; Sin3-associated protein p30-like
• Gene Name: SAP30L
• Related Disease:
  Alzheimer disease
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Clear cell renal carcinoma
• UniProt ID: SP30L_HUMAN
• PDB ID: 2N1U
• Pfam ID: PF13867 ; PF13866
• Sequence:
  MNGFSTEEDSREGPPAAPAAAAPGYGQSCCLIEDGERCVRPAGNASFSKRVQKSISQKKL
  KLDIDKSVRHLYICDFHKNFIQSVRNKRKRKTSDDGGDSPEHDTDIPEVDLFQLQVNTLR
  RYKRHYKLQTRPGFNKAQLAETVSRHFRNIPVNEKETLAYFIYMVKSNKSRLDQKSEGGK
  QLE
• Function: [Isoform 1]: Functions as a transcription repressor, probably via its interaction with histone deacetylase complexes. Involved in the functional recruitment of the class 1 Sin3-histone deacetylase complex (HDAC) to the nucleolus. Binds DNA, apparently without sequence-specificity, and bends bound double-stranded DNA. Binds phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate) via the same basic sequence motif that mediates DNA binding and nuclear import ; [Isoform 2]: Functions as a transcription repressor; isoform 2 has lower transcription repressor activity than isoform 1 and isoform 3; [Isoform 3]: Functions as a transcription repressor; its activity is marginally lower than that of isoform 1.
• Tissue Specificity: Detected in brain and ovary, and at lower levels in heart, small intestine, lung, kidney, skeletal muscle, stomach and spleen (at protein level) . Ubiquitous; expressed in all tissues tested with highest levels in testis .
• KEGG Pathway: Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  Potential therapeutics for SARS (R-HSA-9679191)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Histone deacetylase complex subunit SAP30L (SAP30L).	[15]

References

• [1] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [2] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [3] Long non-coding RNA SAP30L-AS1 promotes prostate cancer growth through repressing SAP30L.Gene. 2019 Mar 30;690:120-128. doi: 10.1016/j.gene.2018.12.047. Epub 2018 Dec 29.
• [4] IDUA, NDST1, SAP30L, CRYBA4, and SI as novel prognostic signatures clear cell renal cell carcinoma.J Cell Physiol. 2019 Sep;234(9):16320-16327. doi: 10.1002/jcp.28297. Epub 2019 Feb 28.
• [5] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] 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.
• [13] 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.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.