Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH7UUV0)

• DOT Name: Urea transporter 1 (SLC14A1)
• Synonyms: Solute carrier family 14 member 1; Urea transporter, erythrocyte
• Gene Name: SLC14A1
• UniProt ID: UT1_HUMAN
• PDB ID: 6QD5; 8BLP
• Pfam ID: PF03253
• Sequence:
  MEDSPTMVRVDSPTMVRGENQVSPCQGRRCFPKALGYVTGDMKELANQLKDKPVVLQFID
  WILRGISQVVFVNNPVSGILILVGLLVQNPWWALTGWLGTVVSTLMALLLSQDRSLIASG
  LYGYNATLVGVLMAVFSDKGDYFWWLLLPVCAMSMTCPIFSSALNSMLSKWDLPVFTLPF
  NMALSMYLSATGHYNPFFPAKLVIPITTAPNISWSDLSALELLKSIPVGVGQIYGCDNPW
  TGGIFLGAILLSSPLMCLHAAIGSLLGIAAGLSLSAPFEDIYFGLWGFNSSLACIAMGGM
  FMALTWQTHLLALGCALFTAYLGVGMANFMAEVGLPACTWPFCLATLLFLIMTTKNSNIY
  KMPLSKVTYPEENRIFYLQAKKRMVESPL
• Function: Mediates the transport of urea driven by a concentration gradient across the cell membrane of erythrocytes. Also mediates the transport of urea across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism. Facilitates water transport in erythrocytes.
• Tissue Specificity: Detected in erythrocytes (at protein level) . Expressed in spleen erythroblasts and tumoral kidney .
• Reactome Pathway: Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Urea transporter 1 (SLC14A1) affects the response to substance of Temozolomide.	[12]
DTI-015	DMXZRW0	Approved	Urea transporter 1 (SLC14A1) affects the response to substance of DTI-015.	[12]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroxyurea	DMOQVU9	Approved	Urea transporter 1 (SLC14A1) increases the uptake of Hydroxyurea.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Urea transporter 1 (SLC14A1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Urea transporter 1 (SLC14A1).	[1]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Urea transporter 1 (SLC14A1).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Urea transporter 1 (SLC14A1).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Urea transporter 1 (SLC14A1).	[4]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Urea transporter 1 (SLC14A1).	[5]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Urea transporter 1 (SLC14A1).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Urea transporter 1 (SLC14A1).	[6]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Urea transporter 1 (SLC14A1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Urea transporter 1 (SLC14A1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Urea transporter 1 (SLC14A1).	[10]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Urea transporter 1 (SLC14A1).	[11]

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 increases the methylation of Urea transporter 1 (SLC14A1).	[8]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] 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.
• [3] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [4] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [5] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [11] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.
• [12] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.
• [13] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.