Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW9XR12)

• DOT Name: Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2 (RPAP2)
• Synonyms: EC 3.1.3.16; RNA polymerase II-associated protein 2
• Gene Name: RPAP2
• Related Disease: Multiple sclerosis
• UniProt ID: RPAP2_HUMAN
• PDB ID: 7B7U; 7F4G
• EC Number: 3.1.3.16
• Pfam ID: PF04181
• Sequence:
  MADFAGPSSAGRKAGAPRCSRKAAGTKQTSTLKQEDASKRKAELEAAVRKKIEFERKALH
  IVEQLLEENITEEFLMECGRFITPAHYSDVVDERSIVKLCGYPLCQKKLGIVPKQKYKIS
  TKTNKVYDITERKSFCSNFCYQASKFFEAQIPKTPVWVREEERHPDFQLLKEEQSGHSGE
  EVQLCSKAIKTSDIDNPSHFEKQYESSSSSTHSDSSSDNEQDFVSSILPGNRPNSTNIRP
  QLHQKSIMKKKAGHKANSKHKDKEQTVVDVTEQLGDCKLDSQEKDATCELPLQKVNTQSS
  SNSTLPERLKASENSESEYSRSEITLVGISKKSAEHFKRKFAKSNQVSRSVSSSVQVCPE
  VGKRNLLKVLKETLIEWKTEETLRFLYGQNYASVCLKPEASLVKEELDEDDIISDPDSHF
  PAWRESQNSLDESLPFRGSGTAIKPLPSYENLKKETEKLNLRIREFYRGRYVLGEETTKS
  QDSEEHDSTFPLIDSSSQNQIRKRIVLEKLSKVLPGLLVPLQITLGDIYTQLKNLVRTFR
  LTNRNIIHKPAEWTLIAMVLLSLLTPILGIQKHSQEGMVFTRFLDTLLEELHLKNEDLES
  LTIIFRTSCLPE
• Function: Protein phosphatase that displays CTD phosphatase activity and regulates transcription of snRNA genes. Recognizes and binds phosphorylated 'Ser-7' of the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and mediates dephosphorylation of 'Ser-5' of the CTD, thereby promoting transcription of snRNA genes. Downstream of EIF2AK3/PERK, dephosphorylates ERN1, a sensor for the endoplasmic reticulum unfolded protein response (UPR), to abort failed ER-stress adaptation and trigger apoptosis.
• Reactome Pathway: RNA polymerase II transcribes snRNA genes (R-HSA-6807505)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[1]

3 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 Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2 (RPAP2).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2 (RPAP2).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2 (RPAP2).	[4]

References

• [1] Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors.Mult Scler. 2016 Dec;22(14):1783-1793. doi: 10.1177/1352458516635873. Epub 2016 Feb 26.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.