Details of Drug Off-Target (DOT)

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

• DOT Name: Ribosomal protein S6 kinase-like 1 (RPS6KL1)
• Synonyms: EC 2.7.11.1
• Gene Name: RPS6KL1
• Related Disease: Anxiety
• UniProt ID: RPKL1_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF04212 ; PF00069
• Sequence:
  MSLVACECLPSPGLEPEPCSRARSQAHVYLEQIRNRVALGVPDMTKRDYLVDAATQIRLA
  LERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFNCHLQR
  PLSSGASPSAGFSSLRLRPIRTLSSAVEQLRGCRVVGVIEKVQLVQDPATGGTFVVKSLP
  RCHMVSRERLTIIPHGVPYMTKLLRYFVSEDSIFLHLEHVQGGTLWSHLLSQAHSRHSGL
  SSGSTQERMKAQLNPHLNLLTPARLPSGHAPGQDRIALEPPRTSPNLLLAGEAPSTRPQR
  EAEGEPTARTSTSGSSDLPKAPGGHLHLQARRAGQNSDAGPPRGLTWVPEGAGPVLGGCG
  RGMDQSCLSADGAGRGCGRATWSVREEQVKQWAAEMLVALEALHEQGVLCRDLHPGNLLL
  DQAGHIRLTYFGQWSEVEPQCCGEAVDNLYSAPEVGGISELTEACDWWSFGSLLYELLTG
  MALSQSHPSGIQAHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHPFFS
  TIQWSKLVG

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Genetic Variation	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Ribosomal protein S6 kinase-like 1 (RPS6KL1) decreases the response to substance of Afimoxifene.	[7]

1 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-like 1 (RPS6KL1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribosomal protein S6 kinase-like 1 (RPS6KL1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ribosomal protein S6 kinase-like 1 (RPS6KL1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribosomal protein S6 kinase-like 1 (RPS6KL1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ribosomal protein S6 kinase-like 1 (RPS6KL1).	[6]

References

• [1] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [2] 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.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] 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.