Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMZB09B)

• DOT Name: TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B)
• Synonyms: RNA polymerase I-specific TBP-associated factor 63 kDa; TAFI63; TATA box-binding protein-associated factor 1B; TBP-associated factor 1B; Transcription initiation factor SL1/TIF-IB subunit B
• Gene Name: TAF1B
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
• UniProt ID: TAF1B_HUMAN
• Pfam ID: PF20645 ; PF20644 ; PF11781
• Sequence:
  MDLEEAEEFKERCTQCAAVSWGLTDEGKYYCTSCHNVTERYQEVTNTDLIPNTQIKALNR
  GLKKKNNTEKGWDWYVCEGFQYILYQQAEALKNLGVGPELKNDVLHNFWKRYLQKSKQAY
  CKNPVYTTGRKPTVLEDNLSHSDWASEPELLSDVSCPPFLESGAESQSDIHTRKPFPVSK
  ASQSETSVCSGSLDGVEYSQRKEKGIVKMTMPQTLAFCYLSLLWQREAITLSDLLRFVEE
  DHIPYINAFQHFPEQMKLYGRDRGIFGIESWPDYEDIYKKTVEVGTFLDLPRFPDITEDC
  YLHPNILCMKYLMEVNLPDEMHSLTCHVVKMTGMGEVDFLTFDPIAKMAKTVKYDVQAVA
  IIVVVLKLLFLLDDSFEWSLSNLAEKHNEKNKKDKPWFDFRKWYQIMKKAFDEKKQKWEE
  ARAKYLWKSEKPLYYSFVDKPVAYKKREMVVNLQKQFSTLVESTATAGKKSPSSFQFNWT
  EEDTDRTCFHGHSLQGVLKEKGQSLLTKNSLYWLSTQKFCRCYCTHVTTYEESNYSLSYQ
  FILNLFSFLLRIKTSLLHEEVSLVEKKLFEKKYSVKRKKSRSKKVRRH
• Function: Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment events in polymerase I (Pol I) transcription. Binds rDNA promoters and plays a role in Pol I recruitment as a component of the SL1/TIF-IB complex and, possibly, directly through its interaction with RRN3.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Limited	Biomarker	[1]

5 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 B (TAF1B).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B).	[7]

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 TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B).	[5]

References

• [1] Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability.Oncogene. 2002 Aug 1;21(33):5081-7. doi: 10.1038/sj.onc.1205703.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] 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.
• [6] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.