Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4HUP9B)

• DOT Name: Transcription factor Sp5 (SP5)
• Gene Name: SP5
• Related Disease:
  Prostate cancer
  Prostate neoplasm
• UniProt ID: SP5_HUMAN
• Pfam ID: PF00096
• Sequence:
  MAAVAVLRNDSLQAFLQDRTPSASPDLGKHSPLALLAATCSRIGQPGAAAPPDFLQVPYD
  PALGSPSRLFHPWTADMPAHSPGALPPPHPSLGLTPQKTHLQPSFGAAHELPLTPPADPS
  YPYEFSPVKMLPSSMAALPASCAPAYVPYAAQAALPPGYSNLLPPPPPPPPPPTCRQLSP
  NPAPDDLPWWSIPQAGAGPGASGVPGSGLSGACAGAPHAPRFPASAAAAAAAAAALQRGL
  VLGPSDFAQYQSQIAALLQTKAPLAATARRCRRCRCPNCQAAGGAPEAEPGKKKQHVCHV
  PGCGKVYGKTSHLKAHLRWHTGERPFVCNWLFCGKSFTRSDELQRHLRTHTGEKRFACPE
  CGKRFMRSDHLAKHVKTHQNKKLKVAEAGVKREDARDL
• Function: Binds to GC boxes promoters elements. Probable transcriptional activator that has a role in the coordination of changes in transcription required to generate pattern in the developing embryo.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcription factor Sp5 (SP5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor Sp5 (SP5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor Sp5 (SP5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor Sp5 (SP5).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor Sp5 (SP5).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transcription factor Sp5 (SP5).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor Sp5 (SP5).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transcription factor Sp5 (SP5).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transcription factor Sp5 (SP5).	[7]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription factor Sp5 (SP5).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription factor Sp5 (SP5).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transcription factor Sp5 (SP5).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor Sp5 (SP5).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Transcription factor Sp5 (SP5).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor Sp5 (SP5).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Transcription factor Sp5 (SP5).	[17]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Transcription factor Sp5 (SP5).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor Sp5 (SP5).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription factor Sp5 (SP5).	[14]

References

• [1] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] 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.
• [10] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [14] 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.
• [15] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [16] 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.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [18] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.