Details of Drug Off-Target (DOT)

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

• DOT Name: Aquaporin-7 (AQP7)
• Synonyms: AQP-7; Aquaglyceroporin-7; Aquaporin adipose; AQPap; Aquaporin-7-like
• Gene Name: AQP7
• UniProt ID: AQP7_HUMAN
• PDB ID: 6KXW; 6N1G; 6QZI; 6QZJ; 8AMW; 8AMX
• Pfam ID: PF00230
• Sequence:
  MVQASGHRRSTRGSKMVSWSVIAKIQEILQRKMVREFLAEFMSTYVMMVFGLGSVAHMVL
  NKKYGSYLGVNLGFGFGVTMGVHVAGRISGAHMNAAVTFANCALGRVPWRKFPVYVLGQF
  LGSFLAAATIYSLFYTAILHFSGGQLMVTGPVATAGIFATYLPDHMTLWRGFLNEAWLTG
  MLQLCLFAITDQENNPALPGTEALVIGILVVIIGVSLGMNTGYAINPSRDLPPRIFTFIA
  GWGKQVFSNGENWWWVPVVAPLLGAYLGGIIYLVFIGSTIPREPLKLEDSVAYEDHGITV
  LPKMGSHEPTISPLTPVSVSPANRSSVHPAPPLHESMALEHF
• Function: Forms a channel that mediates water and glycerol transport across cell membranes at neutral pH. The channel is also permeable to urea. Plays an important role in body energy homeostasis under conditions that promote lipid catabolism, giving rise to glycerol and free fatty acids. Mediates glycerol export from adipocytes. After release into the blood stream, glycerol is used for gluconeogenesis in the liver to maintain normal blood glucose levels and prevent fasting hypoglycemia. Required for normal glycerol reabsorption in the kidney.
• Tissue Specificity: Detected in the sperm head (at protein level) . Detected in white adipose tissue .
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway:
  Passive transport by Aquaporins (R-HSA-432047)
  Transport of glycerol from adipocytes to the liver by Aquaporins (R-HSA-432030)
• BioCyc Pathway: MetaCyc:ENSG00000165269-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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 Aquaporin-7 (AQP7).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Aquaporin-7 (AQP7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Aquaporin-7 (AQP7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aquaporin-7 (AQP7).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aquaporin-7 (AQP7).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Aquaporin-7 (AQP7).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Aquaporin-7 (AQP7).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Aquaporin-7 (AQP7).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Aquaporin-7 (AQP7).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Aquaporin-7 (AQP7).	[9]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [8] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.