Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK03OZN)

• DOT Name: Long-chain fatty acid transport protein 1 (SLC27A1)
• Synonyms: Arachidonate--CoA ligase; EC 6.2.1.15; Fatty acid transport protein 1; FATP-1; Long-chain-fatty-acid--CoA ligase; EC 6.2.1.3; Solute carrier family 27 member 1; Very long-chain acyl-CoA synthetase; EC 6.2.1.-
• Gene Name: SLC27A1
• UniProt ID: S27A1_HUMAN
• EC Number: 6.2.1.-; 6.2.1.15; 6.2.1.3
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MRAPGAGAASVVSLALLWLLGLPWTWSAAAALGVYVGSGGWRFLRIVCKTARRDLFGLSV
  LIRVRLELRRHQRAGHTIPRIFQAVVQRQPERLALVDAGTGECWTFAQLDAYSNAVANLF
  RQLGFAPGDVVAIFLEGRPEFVGLWLGLAKAGMEAALLNVNLRREPLAFCLGTSGAKALI
  FGGEMVAAVAEVSGHLGKSLIKFCSGDLGPEGILPDTHLLDPLLKEASTAPLAQIPSKGM
  DDRLFYIYTSGTTGLPKAAIVVHSRYYRMAAFGHHAYRMQAADVLYDCLPLYHSAGNIIG
  VGQCLIYGLTVVLRKKFSASRFWDDCIKYNCTVVQYIGEICRYLLKQPVREAERRHRVRL
  AVGNGLRPAIWEEFTERFGVRQIGEFYGATECNCSIANMDGKVGSCGFNSRILPHVYPIR
  LVKVNEDTMELLRDAQGLCIPCQAGEPGLLVGQINQQDPLRRFDGYVSESATSKKIAHSV
  FSKGDSAYLSGDVLVMDELGYMYFRDRSGDTFRWRGENVSTTEVEGVLSRLLGQTDVAVY
  GVAVPGVEGKAGMAAVADPHSLLDPNAIYQELQKVLAPYARPIFLRLLPQVDTTGTFKIQ
  KTRLQREGFDPRQTSDRLFFLDLKQGHYLPLNEAVYTRICSGAFAL
• Function: Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane. 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. May act directly as a bona fide transporter, or alternatively, in a cytoplasmic or membrane-associated multimeric protein complex to trap and draw fatty acids towards accumulation. Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis. May be involved in regulation of cholesterol metabolism. Probably involved in fatty acid transport across the blood barrier.
• Tissue Specificity: Highest levels of expression are detected in muscle and adipose tissue small, intermediate levels in small intestine, and barely detectable in liver . Expressed in brain gray matter .
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Insulin resistance (hsa04931)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway:
  Transport of fatty acids (R-HSA-804914)
  PPARA activates gene expression (R-HSA-1989781)

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
3-iodothyronamine	DM3L0F8	Investigative	Long-chain fatty acid transport protein 1 (SLC27A1) affects the uptake of 3-iodothyronamine.	[17]

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 Long-chain fatty acid transport protein 1 (SLC27A1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[11]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[13]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Long-chain fatty acid transport protein 1 (SLC27A1).	[16]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia. 2005 Jan;48(1):83-95. doi: 10.1007/s00125-004-1619-9. Epub 2004 Dec 24.
• [11] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [12] Induction of the fatty acid transport protein 1 and acyl-CoA synthase genes by dimer-selective rexinoids suggests that the peroxisome proliferator-activated receptor-retinoid X receptor heterodimer is their molecular target. J Biol Chem. 2000 Apr 28;275(17):12612-8. doi: 10.1074/jbc.275.17.12612.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [17] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.