Details of Drug Off-Target (DOT)

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

• DOT Name: Potassium-transporting ATPase alpha chain 2 (ATP12A)
• Synonyms: HK alpha 2; Non-gastric H(+)/K(+) ATPase subunit alpha; EC 7.2.2.19; Non-gastric Na(+)/K(+) ATPase subunit alpha; EC 7.2.2.13; Proton pump; Sodium pump
• Gene Name: ATP12A
• UniProt ID: AT12A_HUMAN
• EC Number: 7.2.2.13; 7.2.2.19
• Pfam ID: PF13246 ; PF00689 ; PF00690 ; PF00122 ; PF00702
• Sequence:
  MHQKTPEIYSVELSGTKDIVKTDKGDGKEKYRGLKNNCLELKKKNHKEEFQKELHLDDHK
  LSNRELEEKYGTDIIMGLSSTRAAELLARDGPNSLTPPKQTPEIVKFLKQMVGGFSILLW
  VGAFLCWIAYGIQYSSDKSASLNNVYLGCVLGLVVILTGIFAYYQEAKSTNIMSSFNKMI
  PQQALVIRDSEKKTIPSEQLVVGDIVEVKGGDQIPADIRVLSSQGCRVDNSSLTGESEPQ
  PRSSEFTHENPLETKNICFYSTTCLEGTVTGMVINTGDRTIIGHIASLASGVGNEKTPIA
  IEIEHFVHIVAGVAVSIGILFFIIAVSLKYQVLDSIIFLIGIIVANVPEGLLATVTVTLS
  LTAKRMAKKNCLVKNLEAVETLGSTSIICSDKTGTLTQNRMTVAHLWFDNQIFVADTSED
  HSNQVFDQSSRTWASLSKIITLCNRAEFKPGQENVPIMKKAVIGDASETALLKFSEVILG
  DVMEIRKRNRKVAEIPFNSTNKFQLSIHEMDDPHGKRFLMVMKGAPERILEKCSTIMING
  EEHPLDKSTAKTFHTAYMELGGLGERVLGFCHLYLPADEFPETYSFDIDAMNFPTSNLCF
  VGLLSMIDPPRSTVPDAVTKCRSAGIKVIMVTGDHPITAKAIAKSVGIISANSETVEDIA
  HRLNIAVEQVNKRDAKAAVVTGMELKDMSSEQLDEILANYQEIVFARTSPQQKLIIVEGC
  QRQDAVVAVTGDGVNDSPALKKADIGIAMGIAGSDAAKNAADMVLLDDNFASIVTGVEEG
  RLIFDNLKKTIAYSLTKNIAELCPFLIYIIVGLPLPIGTITILFIDLGTDIIPSIALAYE
  KAESDIMNRKPRHKNKDRLVNQPLAVYSYLHIGLMQALGAFLVYFTVYAQEGFLPRTLIN
  LRVEWEKDYVNDLKDSYGQEWTRYQREYLEWTGYTAFFVGILVQQIADLIIRKTRRNSIF
  QQGLFRNKVIWVGITSQIIIGLILSYGLGSVTALSFTMLRAQYWFVAVPHAILIWVYDEV
  RKLFIRLYPGSWWDKNMYY
• Function: The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment. Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon. In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance.
• Tissue Specificity: Expressed in airway epithelial cells (at protein level) . Found in skin and kidney. Detected in prostate basal cells (at protein level). Expression is increased in benign prostate hyperplasia and tumor tissues (at protein level).
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Omeprazole	DM471KJ	Approved	Potassium-transporting ATPase alpha chain 2 (ATP12A) increases the Gastric pH decreased ADR of Omeprazole.	[8]

2 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 Potassium-transporting ATPase alpha chain 2 (ATP12A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Potassium-transporting ATPase alpha chain 2 (ATP12A).	[5]

5 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 Potassium-transporting ATPase alpha chain 2 (ATP12A).	[2]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Potassium-transporting ATPase alpha chain 2 (ATP12A).	[3]
Capecitabine	DMTS85L	Approved	Capecitabine increases the expression of Potassium-transporting ATPase alpha chain 2 (ATP12A).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Potassium-transporting ATPase alpha chain 2 (ATP12A).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Potassium-transporting ATPase alpha chain 2 (ATP12A).	[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] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [4] Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
• [5] 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.
• [6] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.