Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7JEG5F)

DOT Name Long-chain fatty acid transport protein 2 (SLC27A2)
Synonyms
Arachidonate--CoA ligase; EC 6.2.1.15; Fatty acid transport protein 2; FATP-2; Fatty-acid-coenzyme A ligase, very long-chain 1; Long-chain-fatty-acid--CoA ligase; EC 6.2.1.3; Phytanate--CoA ligase; EC 6.2.1.24; Solute carrier family 27 member 2; THCA-CoA ligase; EC 6.2.1.7; Very long-chain acyl-CoA synthetase; VLACS; VLCS; EC 6.2.1.-; Very long-chain-fatty-acid-CoA ligase
Gene Name SLC27A2
UniProt ID
S27A2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
6.2.1.-; 6.2.1.15; 6.2.1.24; 6.2.1.3; 6.2.1.7
Pfam ID
PF00501 ; PF13193
Sequence
MLSAIYTVLAGLLFLPLLVNLCCPYFFQDIGYFLKVAAVGRRVRSYGKRRPARTILRAFL
EKARQTPHKPFLLFRDETLTYAQVDRRSNQVARALHDHLGLRQGDCVALLMGNEPAYVWL
WLGLVKLGCAMACLNYNIRAKSLLHCFQCCGAKVLLVSPELQAAVEEILPSLKKDDVSIY
YVSRTSNTDGIDSFLDKVDEVSTEPIPESWRSEVTFSTPALYIYTSGTTGLPKAAMITHQ
RIWYGTGLTFVSGLKADDVIYITLPFYHSAALLIGIHGCIVAGATLALRTKFSASQFWDD
CRKYNVTVIQYIGELLRYLCNSPQKPNDRDHKVRLALGNGLRGDVWRQFVKRFGDICIYE
FYAATEGNIGFMNYARKVGAVGRVNYLQKKIITYDLIKYDVEKDEPVRDENGYCVRVPKG
EVGLLVCKITQLTPFNGYAGAKAQTEKKKLRDVFKKGDLYFNSGDLLMVDHENFIYFHDR
VGDTFRWKGENVATTEVADTVGLVDFVQEVNVYGVHVPDHEGRIGMASIKMKENHEFDGK
KLFQHIADYLPSYARPRFLRIQDTIEITGTFKHRKMTLVEEGFNPAVIKDALYFLDDTAK
MYVPMTEDIYNAISAKTLKL
Function
Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes, playing an important role in hepatic fatty acid uptake. Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake. Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis. Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid. May contribute to the synthesis of sphingosine-1-phosphate. Does not activate C24 bile acids, cholate and chenodeoxycholate. In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. However, it is not critical for THCA activation and bile synthesis in vivo ; [Isoform 1]: Exhibits both long-chain fatty acids (LCFA) transport activity and acyl CoA synthetase towards very long-chain fatty acids. Shows a preference for generating CoA derivatives of n-3 fatty acids, which are preferentially trafficked into phosphatidylinositol ; [Isoform 2]: Exhibits long-chain fatty acids (LCFA) transport activity but lacks acyl CoA synthetase towards very long-chain fatty acids.
Tissue Specificity
.Expressed in liver, kidney, placenta, intestine, brain, heart, and colon . Predominantly expressed in liver .; [Isoform 2]: Expressed in liver, placenta, and intestine, but much lower relative to isoform 1.
KEGG Pathway
PPAR sig.ling pathway (hsa03320 )
Peroxisome (hsa04146 )
Insulin resistance (hsa04931 )
Reactome Pathway
Synthesis of bile acids and bile salts via 24-hydroxycholesterol (R-HSA-193775 )
Alpha-oxidation of phytanate (R-HSA-389599 )
Neutrophil degranulation (R-HSA-6798695 )
Fatty acyl-CoA biosynthesis (R-HSA-75105 )
Peroxisomal protein import (R-HSA-9033241 )
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368 )
BioCyc Pathway
MetaCyc:HS06695-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
29 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 Long-chain fatty acid transport protein 2 (SLC27A2). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [5]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [6]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [10]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [11]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [12]
Phenobarbital DMXZOCG Approved Phenobarbital increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [13]
Menadione DMSJDTY Approved Menadione affects the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [14]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [15]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [16]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [17]
Cidofovir DMA13GD Approved Cidofovir decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [16]
Fenofibrate DMFKXDY Approved Fenofibrate increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [18]
Rifampicin DM5DSFZ Approved Rifampicin increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [19]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [20]
Adefovir dipivoxil DMMAWY1 Approved Adefovir dipivoxil decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [16]
Olanzapine DMPFN6Y Approved Olanzapine increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [21]
Vitamin B3 DMQVRZH Approved Vitamin B3 increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [22]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [23]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [24]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [25]
GW7647 DM9RD0C Investigative GW7647 increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [26]
Farnesol DMV2X1B Investigative Farnesol increases the expression of Long-chain fatty acid transport protein 2 (SLC27A2). [26]
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⏷ Show the Full List of 29 Drug(s)

References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 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.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
8 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
9 Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
10 Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
11 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
12 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
13 Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
14 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
15 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
16 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
17 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.
18 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
19 Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
20 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
21 Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019 Nov;316:183-193. doi: 10.1016/j.toxlet.2019.08.013. Epub 2019 Aug 19.
22 Structure-dependent effects of pyridine derivatives on mechanisms of intestinal fatty acid uptake: regulation of nicotinic acid receptor and fatty acid transporter expression. J Nutr Biochem. 2014 Jul;25(7):750-7. doi: 10.1016/j.jnutbio.2014.03.002. Epub 2014 Mar 22.
23 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
24 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
25 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
26 Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.