Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6MR9Z)

• DOT Name: Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1)
• Synonyms: SAPS domain family member 1
• Gene Name: PPP6R1
• UniProt ID: PP6R1_HUMAN
• Pfam ID: PF04499
• Sequence:
  MFWKFDLHTSSHLDTLLEREDLSLPELLDEEDVLQECKVVNRKLLDFLLQPPHLQAMVAW
  VTQEPPDSGEERLRYKYPSVACEILTSDVPQINDALGADESLLNRLYGFLQSTGSLNPLL
  ASFFSKVMGILINRKTDQLVSFLRKKDDFVDLLLQHIGTSAIMDLLLRLLTCVERPQLRQ
  DVVNWLNEEKIVQRLIEQIHPSKDENQHSNASQSLCDIIRLSREQMIQVQDSPEPDQLLA
  TLEKQETIEQLLSNMFEGEQSQSVIVSGIQVLLTLLEPRRPRSESVTVNSFFSSVDGQLE
  LLAQGALESTVSSVGALHALRPRLSCFHQLLLEPPKLEPLQMTWGMLAPPLGNTRLHVVK
  LLASALSANDAALTHELLALDVPNTMLDLFFHYVFNNFLHAQVEGCVSTMLSLGPPPDSS
  PETPIQNPVVKHLLQQCRLVERILTSWEENDRVQCAGGPRKGYMGHLTRVAGALVQNTEK
  GPNAEQLRQLLKELPSEQQEQWEAFVSGPLAETNKKNMVDLVNTHHLHSSSDDEDDRLKE
  FNFPEEAVLQQAFMDFQMQRMTSAFIDHFGFNDEEFGEQEESVNAPFDKTANITFSLNAD
  DENPNANLLEICYKDRIQQFDDDEEEEDEEEAQGSGESDGEDGAWQGSQLARGARLGQPP
  GVRSGGSTDSEDEEEEDEEEEEDEEGIGCAARGGATPLSYPSPGPQPPGPSWTATFDPVP
  TDAPTSPRVSGEEELHTGPPAPQGPLSVPQGLPTQSLASPPARDALQLRSQDPTPPSAPQ
  EATEGSKVTEPSAPCQALVSIGDLQATFHGIRSAPSSSDSATRDPSTSVPASGAHQPPQT
  TEGEKSPEPLGLPQSQSAQALTPPPIPNGSAPEGPASPGSQ
• Function: Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha.
• Tissue Specificity: Ubiquitous with higher expression in testis.
• Reactome Pathway: COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/threonine-protein phosphatase 6 regulatory subunit 1 (PPP6R1).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.