General Information of Drug Off-Target (DOT) (ID: OTJZG0LD)

DOT Name Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4)
Synonyms Glucose transporter type 4, insulin-responsive; GLUT-4
Gene Name SLC2A4
UniProt ID
GLUT4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7WSM; 7WSN
Pfam ID
PF00083
Sequence
MPSGFQQIGSEDGEPPQQRVTGTLVLAVFSAVLGSLQFGYNIGVINAPQKVIEQSYNETW
LGRQGPEGPSSIPPGTLTTLWALSVAIFSVGGMISSFLIGIISQWLGRKRAMLVNNVLAV
LGGSLMGLANAAASYEMLILGRFLIGAYSGLTSGLVPMYVGEIAPTHLRGALGTLNQLAI
VIGILIAQVLGLESLLGTASLWPLLLGLTVLPALLQLVLLPFCPESPRYLYIIQNLEGPA
RKSLKRLTGWADVSGVLAELKDEKRKLERERPLSLLQLLGSRTHRQPLIIAVVLQLSQQL
SGINAVFYYSTSIFETAGVGQPAYATIGAGVVNTVFTLVSVLLVERAGRRTLHLLGLAGM
CGCAILMTVALLLLERVPAMSYVSIVAIFGFVAFFEIGPGPIPWFIVAELFSQGPRPAAM
AVAGFSNWTSNFIIGMGFQYVAEAMGPYVFLLFAVLLLGFFIFTFLRVPETRGRTFDQIS
AAFHRTPSLLEQEVKPSTELEYLGPDEND
Function
Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of insulin, it is efficiently retained intracellularly within storage compartments in muscle and fat cells. Upon insulin stimulation, translocates from these compartments to the cell surface where it transports glucose from the extracellular milieu into the cell.
Tissue Specificity Skeletal and cardiac muscles; brown and white fat.
KEGG Pathway
FoxO sig.ling pathway (hsa04068 )
AMPK sig.ling pathway (hsa04152 )
Insulin sig.ling pathway (hsa04910 )
Adipocytokine sig.ling pathway (hsa04920 )
Type II diabetes mellitus (hsa04930 )
Insulin resistance (hsa04931 )
Diabetic cardiomyopathy (hsa05415 )
Reactome Pathway
Cellular hexose transport (R-HSA-189200 )
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Troglitazone DM3VFPD Approved Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4) increases the Drug dependence ADR of Troglitazone. [22]
Glipizide DMZA5PQ Approved Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4) increases the Liver disorder ADR of Glipizide. [22]
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This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Adenosine triphosphate DM79F6G Approved Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4) increases the abundance of Adenosine triphosphate. [23]
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23 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [1]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [2]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [3]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [4]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [5]
Testosterone DM7HUNW Approved Testosterone increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [5]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [6]
Dexamethasone DMMWZET Approved Dexamethasone affects the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [7]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [8]
Zidovudine DM4KI7O Approved Zidovudine affects the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [9]
Haloperidol DM96SE0 Approved Haloperidol increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [10]
Olanzapine DMPFN6Y Approved Olanzapine increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [10]
Glucosamine DM4ZLFD Approved Glucosamine decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [11]
Fructose DM43AN2 Approved Fructose decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [12]
Mirtazapine DML53ZJ Approved Mirtazapine increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [10]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [15]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [18]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [19]
D-glucose DMMG2TO Investigative D-glucose decreases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [20]
P-Coumaric Acid DMGJSVD Investigative P-Coumaric Acid increases the expression of Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [21]
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⏷ Show the Full List of 23 Drug(s)
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 Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4). [14]
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References

1 Valproic acid promotes mitochondrial dysfunction in primary human hepatocytes in vitro; impact of C/EBP-controlled gene expression. Arch Toxicol. 2020 Oct;94(10):3463-3473. doi: 10.1007/s00204-020-02835-x. Epub 2020 Jul 4.
2 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.
3 Oestradiol and SERM treatments influence oestrogen receptor coregulator gene expression in human skeletal muscle cells. Acta Physiol (Oxf). 2009 Nov;197(3):187-96. doi: 10.1111/j.1748-1716.2009.01997.x. Epub 2009 May 6.
4 Combined effects of arsenic and palmitic acid on oxidative stress and lipid metabolism disorder in human hepatoma HepG2 cells. Sci Total Environ. 2021 May 15;769:144849. doi: 10.1016/j.scitotenv.2020.144849. Epub 2021 Jan 19.
5 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
6 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
7 Anti-diabetic effect of oligosaccharides from seaweed Sargassum confusum via JNK-IRS1/PI3K signalling pathways and regulation of gut microbiota. Food Chem Toxicol. 2019 Sep;131:110562. doi: 10.1016/j.fct.2019.110562. Epub 2019 Jun 7.
8 Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1. Diabetologia. 2005 Jun;48(6):1173-9. doi: 10.1007/s00125-005-1741-3. Epub 2005 Apr 30.
9 Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months. Antivir Ther. 2009;14(8):1089-100. doi: 10.3851/IMP1457.
10 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.
11 Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells. Diabetologia. 2010 May;53(5):955-65. doi: 10.1007/s00125-010-1676-1. Epub 2010 Feb 18.
12 Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men. Diabetes Metab. 2008 Feb;34(1):82-5. doi: 10.1016/j.diabet.2007.08.004. Epub 2007 Dec 11.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 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.
15 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
16 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
17 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.
18 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
19 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
20 Faster lipid -oxidation rate by acetyl-CoA carboxylase 2 inhibition alleviates high-glucose-induced insulin resistance via SIRT1/PGC-1 in human podocytes. J Biochem Mol Toxicol. 2021 Jul;35(7):e22797. doi: 10.1002/jbt.22797. Epub 2021 May 6.
21 Procyanidin B1 and p-Coumaric Acid from Highland Barley Grain Showed Synergistic Effect on Modulating Glucose Metabolism via IRS-1/PI3K/Akt Pathway. Mol Nutr Food Res. 2021 Sep;65(18):e2100454. doi: 10.1002/mnfr.202100454. Epub 2021 Aug 16.
22 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.
23 Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation. Environ Toxicol. 2022 Apr;37(4):754-764. doi: 10.1002/tox.23440. Epub 2021 Dec 14.