Details of Drug Off-Target (DOT)

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

• DOT Name: Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5)
• Synonyms: Fructose transporter; Glucose transporter type 5, small intestine; GLUT-5
• Gene Name: SLC2A5
• UniProt ID: GTR5_HUMAN
• Pfam ID: PF00083
• Sequence:
  MEQQDQSMKEGRLTLVLALATLIAAFGSSFQYGYNVAAVNSPALLMQQFYNETYYGRTGE
  FMEDFPLTLLWSVTVSMFPFGGFIGSLLVGPLVNKFGRKGALLFNNIFSIVPAILMGCSR
  VATSFELIIISRLLVGICAGVSSNVVPMYLGELAPKNLRGALGVVPQLFITVGILVAQIF
  GLRNLLANVDGWPILLGLTGVPAALQLLLLPFFPESPRYLLIQKKDEAAAKKALQTLRGW
  DSVDREVAEIRQEDEAEKAAGFISVLKLFRMRSLRWQLLSIIVLMGGQQLSGVNAIYYYA
  DQIYLSAGVPEEHVQYVTAGTGAVNVVMTFCAVFVVELLGRRLLLLLGFSICLIACCVLT
  AALALQDTVSWMPYISIVCVISYVIGHALGPSPIPALLITEIFLQSSRPSAFMVGGSVHW
  LSNFTVGLIFPFIQEGLGPYSFIVFAVICLLTTIYIFLIVPETKAKTFIEINQIFTKMNK
  VSEVYPEKEELKELPPVTSEQ
• Function: Functions as a fructose transporter that has only low activity with other monosaccharides. Can mediate the uptake of 2-deoxyglucose, but with low efficiency. Essential for fructose uptake in the small intestine. Plays a role in the regulation of salt uptake and blood pressure in response to dietary fructose. Required for the development of high blood pressure in response to high dietary fructose intake.
• Tissue Specificity: Detected in skeletal muscle, and in jejunum brush border membrane and basolateral membrane (at protein level) . Expressed in small intestine, and at much lower levels in kidney, skeletal muscle, and adipose tissue.
• KEGG Pathway: Carbohydrate digestion and absorption (hsa04973)
• Reactome Pathway:
  Intestinal hexose absorption (R-HSA-8981373)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:ENSG00000142583-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5) increases the transport of Arsenic.	[4]

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 Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[7]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[8]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[9]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[10]
Fructose	DM43AN2	Approved	Fructose increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[11]
Mirtazapine	DML53ZJ	Approved	Mirtazapine increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[12]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[17]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[11]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[11]
[3H]cAMP	DMZRQU7	Investigative	[3H]cAMP affects the expression of Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5).	[18]

References

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• [2] 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.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [9] Microglial and astrocytic changes in the striatum of methamphetamine abusers. Leg Med (Tokyo). 2010 Mar;12(2):57-62. doi: 10.1016/j.legalmed.2009.11.001. Epub 2010 Jan 27.
• [10] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [11] Fructose modulates GLUT5 mRNA stability in differentiated Caco-2 cells: role of cAMP-signalling pathway and PABP (polyadenylated-binding protein)-interacting protein (Paip) 2. Biochem J. 2003 Oct 1;375(Pt 1):167-74. doi: 10.1042/BJ20030661.
• [12] Effects of different antipsychotics and the antidepressant mirtazapine on glucose transporter mRNA levels in human blood cells. J Psychiatr Res. 2006 Jun;40(4):374-9. doi: 10.1016/j.jpsychires.2005.04.016. Epub 2005 Jul 5.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [16] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] Sugar-dependent expression of the fructose transporter GLUT5 in Caco-2 cells. Biochem J. 1995 Dec 15;312 ( Pt 3)(Pt 3):757-62. doi: 10.1042/bj3120757.