Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCP6ZYD)

• DOT Name: TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L)
• Synonyms: TAF5L; PCAF-associated factor 65 beta; PAF65-beta
• Gene Name: TAF5L
• Related Disease:
  Type-1/2 diabetes
  Breast neoplasm
• UniProt ID: TAF5L_HUMAN
• PDB ID: 7KTR; 7KTS; 8H7G
• Pfam ID: PF04494 ; PF00400
• Sequence:
  MKRVRTEQIQMAVSCYLKRRQYVDSDGPLKQGLRLSQTAEEMAANLTVQSESGCANIVSA
  APCQAEPQQYEVQFGRLRNFLTDSDSQHSHEVMPLLYPLFVYLHLNLVQNSPKSTVESFY
  SRFHGMFLQNASQKDVIEQLQTTQTIQDILSNFKLRAFLDNKYVVRLQEDSYNYLIRYLQ
  SDNNTALCKVLTLHIHLDVQPAKRTDYQLYASGSSSRSENNGLEPPDMPSPILQNEAALE
  VLQESIKRVKDGPPSLTTICFYAFYNTEQLLNTAEISPDSKLLAAGFDNSCIKLWSLRSK
  KLKSEPHQVDVSRIHLACDILEEEDDEDDNAGTEMKILRGHCGPVYSTRFLADSSGLLSC
  SEDMSIRYWDLGSFTNTVLYQGHAYPVWDLDISPYSLYFASGSHDRTARLWSFDRTYPLR
  IYAGHLADVDCVKFHPNSNYLATGSTDKTVRLWSAQQGNSVRLFTGHRGPVLSLAFSPNG
  KYLASAGEDQRLKLWDLASGTLYKELRGHTDNITSLTFSPDSGLIASASMDNSVRVWDIR
  NTYCSAPADGSSSELVGVYTGQMSNVLSVQFMACNLLLVTGITQENQEH
• Function: Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex (Probable). With TAF6L, acts as an epigenetic regulator essential for somatic reprogramming. Regulates target genes through H3K9ac deposition and MYC recruitment which trigger MYC regulatory network to orchestrate gene expression programs to control embryonic stem cell state.
• KEGG Pathway: Basal transcription factors (hsa03022)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[1]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[2]

13 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 TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[10]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[10]

1 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 decreases the methylation of TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L (TAF5L).	[14]

References

• [1] The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients.Autoimmunity. 2005 Jun;38(4):283-93. doi: 10.1080/08916930500128594.
• [2] High levels of -glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer.BMC Cancer. 2013 Feb 1;13:47. doi: 10.1186/1471-2407-13-47.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] 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.