Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEH7OFT)

• DOT Name: TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A)
• Synonyms: RNA polymerase I-specific TBP-associated factor 48 kDa; TAFI48; TATA box-binding protein-associated factor 1A; TBP-associated factor 1A; Transcription factor SL1; Transcription initiation factor SL1/TIF-IB subunit A
• Gene Name: TAF1A
• Related Disease:
  Cataract
  Dilated cardiomyopathy
  Obsolete familial isolated dilated cardiomyopathy
  Familial dilated cardiomyopathy
• UniProt ID: TAF1A_HUMAN
• Pfam ID: PF14929
• Sequence:
  MSDFSEELKGPVTDDEEVETSVLSGAGMHFPWLQTYVETVAIGGKRRKDFAQTTSACLSF
  IQEALLKHQWQQAAEYMYSYFQTLEDSDSYKRQAAPEIIWKLGSEILFYHPKSNMESFNT
  FANRMKNIGVMNYLKISLQHALYLLHHGMLKDAKRNLSEAETWRHGENTSSREILINLIQ
  AYKGLLQYYTWSEKKMELSKLDKDDYAYNAVAQDVFNHSWKTSANISALIKIPGVWDPFV
  KSYVEMLEFYGDRDGAQEVLTNYAYDEKFPSNPNAHIYLYNFLKRQKAPRSKLISVLKIL
  YQIVPSHKLMLEFHTLLRKSEKEEHRKLGLEVLFGVLDFAGCTKNITAWKYLAKYLKNIL
  MGNHLAWVQEEWNSRKNWWPGFHFSYFWAKSDWKEDTALACEKAFVAGLLLGKGCRYFRY
  ILKQDHQILGKKIKRMKRSVKKYSIVNPRL
• Function: Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  B-WICH complex positively regulates rRNA expression (R-HSA-5250924)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  RNA Polymerase I Promoter Escape (R-HSA-73772)
  RNA Polymerase I Transcription Termination (R-HSA-73863)
  SIRT1 negatively regulates rRNA expression (R-HSA-427359)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract	DISUD7SL	Strong	Biomarker	[1]
Dilated cardiomyopathy	DISX608J	moderate	Genetic Variation	[2]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[2]
Familial dilated cardiomyopathy	DISBHDU9	Disputed	GermlineCausalMutation	[2]

11 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 TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[10]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[11]
Piperazinyl methyl quinazolinone derivative 2	DM913KS	Patented	Piperazinyl methyl quinazolinone derivative 2 decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A).	[13]

References

• [1] Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.Hum Genet. 2017 Feb;136(2):205-225. doi: 10.1007/s00439-016-1747-6. Epub 2016 Nov 22.
• [2] Recessive TAF1A mutations reveal ribosomopathy in siblings with end-stage pediatric dilated cardiomyopathy. Hum Mol Genet. 2017 Aug 1;26(15):2874-2881. doi: 10.1093/hmg/ddx169.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [11] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [12] A novel circular RNA confers trastuzumab resistance in human epidermal growth factor receptor 2-positive breast cancer through regulating ferroptosis. Environ Toxicol. 2022 Jul;37(7):1597-1607. doi: 10.1002/tox.23509. Epub 2022 Mar 2.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.