Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1QS1KM)

• DOT Name: Ribonuclease kappa (RNASEK)
• Synonyms: RNase K; RNase kappa; EC 3.1.-.-; V-type proton ATPase subunit f; V-ATPase subunit f
• Gene Name: RNASEK
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Non-insulin dependent diabetes
  Type-1/2 diabetes
• UniProt ID: RNK_HUMAN
• PDB ID: 6WLW; 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
• EC Number: 3.1.-.-
• Sequence:
  MGWLRPGPRPLCPPARASWAFSHRFPSPLAPRRSPTPFFMASLLCCGPKLAACGIVLSAW
  GVIMLIMLGIFFNVHSAVLIEDVPFTEKDFENGPQNIYNLYEQVSYNCFIAAGLYLLLGG
  FSFCQVRLNKRKEYMVR
• Function: Endoribonuclease which preferentially cleaves ApU and ApG phosphodiester bonds. Hydrolyzes UpU bonds at a lower rate. Regulates the activity of vacuolar (H+)-ATPase (V-ATPase) which is responsible for acidifying and maintaining the pH of intracellular compartments. Required at an early stage of receptor-mediated endocytosis ; (Microbial infection) Required at an early stage of both clathrin-mediated and clathrin-independent endocytic uptake of a diverse set of viruses, including dengue, West Nile, Sindbis, Rift Valley Fever, influenza, and human rhinoviruses.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[2]

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 Ribonuclease kappa (RNASEK).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ribonuclease kappa (RNASEK).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of Ribonuclease kappa (RNASEK).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ribonuclease kappa (RNASEK).	[6]

References

• [1] Identification of novel alternative transcripts of the human Ribonuclease (RNASEK) gene using 3' RACE and high-throughput sequencing approaches.Genomics. 2020 Jan;112(1):943-951. doi: 10.1016/j.ygeno.2019.06.010. Epub 2019 Jun 11.
• [2] Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression.Diabetes. 2016 Feb;65(2):510-9. doi: 10.2337/db15-0571. Epub 2015 Oct 20.
• [3] 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.
• [4] 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.
• [5] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.