Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXTSHH8)

• DOT Name: DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3)
• Synonyms: RNA polymerase II subunit B11-b1; RPB11b1; DNA-directed RNA polymerase II subunit J2
• Gene Name: POLR2J3
• UniProt ID: RPB1B_HUMAN
• Pfam ID: PF13656
• Sequence:
  MNAPPAFESFLLFEGEKITINKDTKVPKACLFTINKEDHTLGNIIKSQLLKDPQVLFAGY
  KVPHPLEHKIIIRVQTTPDYSPQEAFTNAITDLISELSLLEERFRTCLLPLRLLP
• Function: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  R. polymerase (hsa03020)
  Nucleotide excision repair (hsa03420)
  Huntington disease (hsa05016)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA-directed RNA polymerase II subunit RPB11-b1 (POLR2J3).	[7]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] 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.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [6] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [7] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.