Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1XMYAD)

• DOT Name: Transcription initiation factor TFIID subunit 13 (TAF13)
• Synonyms: Transcription initiation factor TFIID 18 kDa subunit; TAF(II)18; TAFII-18; TAFII18
• Gene Name: TAF13
• Related Disease:
  Intellectual disability
  Neuroblastoma
  Isolated congenital microcephaly
  Autosomal recessive primary microcephaly
  Intellectual disability, autosomal recessive 60
• UniProt ID: TAF13_HUMAN
• PDB ID: 1BH8; 1BH9; 6MZD; 6MZL; 7EDX; 7EG7; 7EG8; 7EG9; 7EGA; 7EGB; 7EGC; 7EGD; 7EGE; 7EGF; 7EGI; 7EGJ; 7ENA; 7ENC; 8GXQ; 8GXS; 8WAK; 8WAL; 8WAN; 8WAO; 8WAP; 8WAQ; 8WAR; 8WAS
• Pfam ID: PF02269
• Sequence:
  MADEEEDPTFEEENEEIGGGAEGGQGKRKRLFSKELRCMMYGFGDDQNPYTESVDILEDL
  VIEFITEMTHKAMSIGRQGRVQVEDIVFLIRKDPRKFARVKDLLTMNEELKRARKAFDEA
  NYGS
• Function: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. TAF13, together with TAF11 and TBP, play key roles during promoter binding by the TFIID and TFIIA transcription factor complexes.
• KEGG Pathway: Basal transcription factors (hsa03022)
• Reactome Pathway:
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)
  RNA Polymerase II Promoter Escape (R-HSA-73776)
  RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  HIV Transcription Initiation (R-HSA-167161)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[1]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[1]
Autosomal recessive primary microcephaly	DIS29IE3	Supportive	Autosomal recessive	[1]
Intellectual disability, autosomal recessive 60	DIST70AC	Limited	Autosomal recessive	[2]

9 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 Transcription initiation factor TFIID subunit 13 (TAF13).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[7]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription initiation factor TFIID subunit 13 (TAF13).	[10]

References

• [1] Hypomorphic Pathogenic Variants in TAF13 Are Associated with Autosomal-Recessive Intellectual Disability and Microcephaly. Am J Hum Genet. 2017 Mar 2;100(3):555-561. doi: 10.1016/j.ajhg.2017.01.032.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.