Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8Q5UWS)

• DOT Name: Aquaporin-10 (AQP10)
• Synonyms: AQP-10; Aquaglyceroporin-10; Small intestine aquaporin
• Gene Name: AQP10
• Related Disease:
  Chronic otitis media
  Breast cancer
  Breast carcinoma
• UniProt ID: AQP10_HUMAN
• PDB ID: 6F7H
• Pfam ID: PF00230
• Sequence:
  MVFTQAPAEIMGHLRIRSLLARQCLAEFLGVFVLMLLTQGAVAQAVTSGETKGNFFTMFL
  AGSLAVTIAIYVGGNVSGAHLNPAFSLAMCIVGRLPWVKLPIYILVQLLSAFCASGATYV
  LYHDALQNYTGGNLTVTGPKETASIFATYPAPYLSLNNGFLDQVLGTGMLIVGLLAILDR
  RNKGVPAGLEPVVVGMLILALGLSMGANCGIPLNPARDLGPRLFTYVAGWGPEVFSAGNG
  WWWVPVVAPLVGATVGTATYQLLVALHHPEGPEPAQDLVSAQHKASELETPASAQMLECK
  L
• Function: [Isoform 1]: Water channel that mediates water transport across cell membranes irrespective of the cytosolic pH. The channel is permeable to glycerol, especially when the cytosolic pH is acidified. Contributes to adipocyte water and glycerol permeability, and may thereby contribute to the utilization of glycerol derived from phospholipid degradation. May contribute to water transport in the intestine (Probable); [Isoform 2]: Water channel that mediates water transport across cell membranes, but that is not permeable to glycerol.
• Tissue Specificity: Detected in epithelial cells on villi in the ileum, and also in stomach, jejunum, colon, rectum, white adipose tissue and placenta (at protein level) . Expressed in duodenum and jejunum. Highest expression in absorptive epithelial cells at the tips of villi in the jejunum . Detected in subcutaneous adipose tissue .
• Reactome Pathway: Passive transport by Aquaporins (R-HSA-432047)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic otitis media	DIS3P3TG	moderate	Altered Expression	[1]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Aquaporin-10 (AQP10) increases the transport of Arsenic.	[4]
Urea	DMUK75B	Approved	Aquaporin-10 (AQP10) increases the uptake of Urea.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aquaporin-10 (AQP10).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Aquaporin-10 (AQP10).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Aquaporin-10 (AQP10).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Aquaporin-10 (AQP10).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Aquaporin-10 (AQP10).	[8]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate affects the expression of Aquaporin-10 (AQP10).	[9]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Aquaporin-10 (AQP10).	[7]

References

• [1] Expression of aquaporins mRNAs in patients with otitis media.Acta Otolaryngol. 2018 Aug;138(8):701-707. doi: 10.1080/00016489.2018.1447685. Epub 2018 Apr 1.
• [2] Significant prognostic values of aquaporin mRNA expression in breast cancer.Cancer Manag Res. 2019 Feb 14;11:1503-1515. doi: 10.2147/CMAR.S193396. eCollection 2019.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] In vitro study of transporters involved in intestinal absorption of inorganic arsenic. Chem Res Toxicol. 2012 Feb 20;25(2):446-53. doi: 10.1021/tx200491f. Epub 2012 Jan 26.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] 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.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] Gene profiles of THP-1 macrophages after in vitro exposure to respiratory (non-)sensitizing chemicals: identification of discriminating genetic markers and pathway analysis. Toxicol In Vitro. 2009 Sep;23(6):1151-62. doi: 10.1016/j.tiv.2009.06.007. Epub 2009 Jun 13.
• [10] In vitro study of transporters involved in intestinal absorption of inorganic arsenic. Chem Res Toxicol. 2012 Feb 20;25(2):446-53. doi: 10.1021/tx200491f. Epub 2012 Jan 26.
• [11] Cloning and identification of a new member of water channel (AQP10) as an aquaglyceroporin. Biochim Biophys Acta. 2002 Jul 19;1576(3):335-40. doi: 10.1016/s0167-4781(02)00393-7.