Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCW17LF)

• DOT Name: RNA polymerase II-associated protein 3 (RPAP3)
• Gene Name: RPAP3
• UniProt ID: RPAP3_HUMAN
• PDB ID: 4CGV; 4CGW; 6EZ4; 6FD7; 6FDP; 6FDT; 6FM8; 6FO1; 6GXZ; 6ZBK
• Pfam ID: PF13877 ; PF00515 ; PF13432 ; PF13181
• Sequence:
  MTSANKAIELQLQVKQNAEELQDFMRDLENWEKDIKQKDMELRRQNGVPEENLPPIRNGN
  FRKKKKGKAKESSKKTREENTKNRIKSYDYEAWAKLDVDRILDELDKDDSTHESLSQESE
  SEEDGIHVDSQKALVLKEKGNKYFKQGKYDEAIDCYTKGMDADPYNPVLPTNRASAYFRL
  KKFAVAESDCNLAVALNRSYTKAYSRRGAARFALQKLEEAKKDYERVLELEPNNFEATNE
  LRKISQALASKENSYPKEADIVIKSTEGERKQIEAQQNKQQAISEKDRGNGFFKEGKYER
  AIECYTRGIAADGANALLPANRAMAYLKIQKYEEAEKDCTQAILLDGSYSKAFARRGTAR
  TFLGKLNEAKQDFETVLLLEPGNKQAVTELSKIKKELIEKGHWDDVFLDSTQRQNVVKPI
  DNPPHPGSTKPLKKVIIEETGNLIQTIDVPDSTTAAAPENNPINLANVIAATGTTSKKNS
  SQDDLFPTSDTPRAKVLKIEEVSDTSSLQPQASLKQDVCQSYSEKMPIEIEQKPAQFATT
  VLPPIPANSFQLESDFRQLKSSPDMLYQYLKQIEPSLYPKLFQKNLDPDVFNQIVKILHD
  FYIEKEKPLLIFEILQRLSELKRFDMAVMFMSETEKKIARALFNHIDKSGLKDSSVEELK
  KRYGG
• Function: Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation.

Molecular Interaction Atlas (MIA) of This DOT

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RNA polymerase II-associated protein 3 (RPAP3).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of RNA polymerase II-associated protein 3 (RPAP3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RNA polymerase II-associated protein 3 (RPAP3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA polymerase II-associated protein 3 (RPAP3).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA polymerase II-associated protein 3 (RPAP3).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RNA polymerase II-associated protein 3 (RPAP3).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of RNA polymerase II-associated protein 3 (RPAP3).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RNA polymerase II-associated protein 3 (RPAP3).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.