Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTY0FI2)

• DOT Name: Ribosomal protein S6 kinase alpha-6 (RPS6KA6)
• Synonyms: S6K-alpha-6; EC 2.7.11.1; 90 kDa ribosomal protein S6 kinase 6; p90-RSK 6; p90RSK6; Ribosomal S6 kinase 4; RSK-4; pp90RSK4
• Gene Name: RPS6KA6
• UniProt ID: KS6A6_HUMAN
• PDB ID: 6G76; 6G77; 6G78
• EC Number: 2.7.11.1
• Pfam ID: PF00069 ; PF00433
• Sequence:
  MLPFAPQDEPWDREMEVFSGGGASSGEVNGLKMVDEPMEEGEADSCHDEGVVKEIPITHH
  VKEGYEKADPAQFELLKVLGQGSFGKVFLVRKKTGPDAGQLYAMKVLKKASLKVRDRVRT
  KMERDILVEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDVFTRLSKEVLFTEEDVKFYLA
  ELALALDHLHQLGIVYRDLKPENILLDEIGHIKLTDFGLSKESVDQEKKAYSFCGTVEYM
  APEVVNRRGHSQSADWWSYGVLMFEMLTGTLPFQGKDRNETMNMILKAKLGMPQFLSAEA
  QSLLRMLFKRNPANRLGSEGVEEIKRHLFFANIDWDKLYKREVQPPFKPASGKPDDTFCF
  DPEFTAKTPKDSPGLPASANAHQLFKGFSFVATSIAEEYKITPITSANVLPIVQINGNAA
  QFGEVYELKEDIGVGSYSVCKRCIHATTNMEFAVKIIDKSKRDPSEEIEILMRYGQHPNI
  ITLKDVFDDGRYVYLVTDLMKGGELLDRILKQKCFSEREASDILYVISKTVDYLHCQGVV
  HRDLKPSNILYMDESASADSIRICDFGFAKQLRGENGLLLTPCYTANFVAPEVLMQQGYD
  AACDIWSLGVLFYTMLAGYTPFANGPNDTPEEILLRIGNGKFSLSGGNWDNISDGAKDLL
  SHMLHMDPHQRYTAEQILKHSWITHRDQLPNDQPKRNDVSHVVKGAMVATYSALTHKTFQ
  PVLEPVAASSLAQRRSMKKRTSTGL
• Function: Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Oocyte meiosis (hsa04114)
  mTOR sig.ling pathway (hsa04150)
  Thermogenesis (hsa04714)
  Long-term potentiation (hsa04720)
  Neurotrophin sig.ling pathway (hsa04722)
  Progesterone-mediated oocyte maturation (hsa04914)
  Insulin resistance (hsa04931)
  Yersinia infection (hsa05135)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling (R-HSA-442742)
  RSK activation (R-HSA-444257)
  Recycling pathway of L1 (R-HSA-437239)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribosomal protein S6 kinase alpha-6 (RPS6KA6).	[1]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Ribosomal protein S6 kinase alpha-6 (RPS6KA6).	[2]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ribosomal protein S6 kinase alpha-6 (RPS6KA6).	[2]

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 increases the methylation of Ribosomal protein S6 kinase alpha-6 (RPS6KA6).	[3]

References

• [1] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] 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.