Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCAK8U8)

• DOT Name: Ribosomal protein S6 kinase beta-2 (RPS6KB2)
• Synonyms: S6K-beta-2; S6K2; EC 2.7.11.1; 70 kDa ribosomal protein S6 kinase 2; P70S6K2; p70-S6K 2; S6 kinase-related kinase; SRK; Serine/threonine-protein kinase 14B; p70 ribosomal S6 kinase beta; S6K-beta; p70 S6 kinase beta; p70 S6K-beta; p70 S6KB; p70-beta
• Gene Name: RPS6KB2
• UniProt ID: KS6B2_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069 ; PF00433
• Sequence:
  MAAVFDLDLETEEGSEGEGEPELSPADACPLAELRAAGLEPVGHYEEVELTETSVNVGPE
  RIGPHCFELLRVLGKGGYGKVFQVRKVQGTNLGKIYAMKVLRKAKIVRNAKDTAHTRAER
  NILESVKHPFIVELAYAFQTGGKLYLILECLSGGELFTHLEREGIFLEDTACFYLAEITL
  ALGHLHSQGIIYRDLKPENIMLSSQGHIKLTDFGLCKESIHEGAVTHTFCGTIEYMAPEI
  LVRSGHNRAVDWWSLGALMYDMLTGSPPFTAENRKKTMDKIIRGKLALPPYLTPDARDLV
  KKFLKRNPSQRIGGGPGDAADVQRHPFFRHMNWDDLLAWRVDPPFRPCLQSEEDVSQFDT
  RFTRQTPVDSPDDTALSESANQAFLGFTYVAPSVLDSIKEGFSFQPKLRSPRRLNSSPRA
  PVSPLKFSPFEGFRPSPSLPEPTELPLPPLLPPPPPSTTAPLPIRPPSGTKKSKRGRGRP
  GR
• Function: Phosphorylates specifically ribosomal protein S6. Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  ErbB sig.ling pathway (hsa04012)
  HIF-1 sig.ling pathway (hsa04066)
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  TGF-beta sig.ling pathway (hsa04350)
  Apelin sig.ling pathway (hsa04371)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Thermogenesis (hsa04714)
  Insulin sig.ling pathway (hsa04910)
  Insulin resistance (hsa04931)
  Shigellosis (hsa05131)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
  Acute myeloid leukemia (hsa05221)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Choline metabolism in cancer (hsa05231)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
• Reactome Pathway:
  Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400)
  AKT phosphorylates targets in the nucleus (R-HSA-198693)

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 increases the methylation of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[4]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[3]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the activity of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[6]
Myricetin	DMTV4L0	Investigative	Myricetin increases the expression of Ribosomal protein S6 kinase beta-2 (RPS6KB2).	[7]

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] 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.
• [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] 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.
• [5] 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.
• [6] Regulation of ribosomal S6 kinase 2 by mammalian target of rapamycin. J Biol Chem. 2002 Aug 30;277(35):31423-9. doi: 10.1074/jbc.M204080200. Epub 2002 Jun 26.
• [7] Potential role of nucleoside diphosphate kinase in myricetin-induced selective apoptosis in colon cancer HCT-15?cells. Food Chem Toxicol. 2018 Jun;116(Pt B):315-322. doi: 10.1016/j.fct.2018.04.053. Epub 2018 Apr 24.