Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2AJU6L)

• DOT Name: Long-chain fatty acid transport protein 6 (SLC27A6)
• Synonyms: FATP-6; Fatty acid transport protein 6; Arachidonate--CoA ligase; EC 6.2.1.15; Fatty-acid-coenzyme A ligase, very long-chain 2; Long-chain-fatty-acid--CoA ligase; EC 6.2.1.3; Solute carrier family 27 member 6; Very long-chain acyl-CoA synthetase homolog 1; VLCSH1; hVLCS-H1; EC 6.2.1.-
• Gene Name: SLC27A6
• UniProt ID: S27A6_HUMAN
• EC Number: 6.2.1.-; 6.2.1.15; 6.2.1.3
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MLLSWLTVLGAGMVVLHFLQKLLFPYFWDDFWFVLKVVLIIIRLKKYEKRGELVTVLDKF
  LSHAKRQPRKPFIIYEGDIYTYQDVDKRSSRVAHVFLNHSSLKKGDTVALLMSNEPDFVH
  VWFGLAKLGCVVAFLNTNIRSNSLLNCIRACGPRALVVGADLLGTVEEILPSLSENISVW
  GMKDSVPQGVISLKEKLSTSPDEPVPRSHHVVSLLKSTCLYIFTSGTTGLPKAAVISQLQ
  VLRGSAVLWAFGCTAHDIVYITLPLYHSSAAILGISGCVELGATCVLKKKFSASQFWSDC
  KKYDVTVFQYIGELCRYLCKQSKREGEKDHKVRLAIGNGIRSDVWREFLDRFGNIKVCEL
  YAATESSISFMNYTGRIGAIGRTNLFYKLLSTFDLIKYDFQKDEPMRNEQGWCIHVKKGE
  PGLLISRVNAKNPFFGYAGPYKHTKDKLLCDVFKKGDVYLNTGDLIVQDQDNFLYFWDRT
  GDTFRWKGENVATTEVADVIGMLDFIQEANVYGVAISGYEGRAGMASIILKPNTSLDLEK
  VYEQVVTFLPAYACPRFLRIQEKMEATGTFKLLKHQLVEDGFNPLKISEPLYFMDNLKKS
  YVLLTRELYDQIMLGEIKL
• 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. Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation such as the heart.
• Tissue Specificity: Strongly expressed in heart and localizes to cardiac myocytes . Expressed at moderate levels in placenta, testis, and adrenal glands. Expressed at very low levels in kidney, bladder and uterus.
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Insulin resistance (hsa04931)
• Reactome Pathway: Transport of fatty acids (R-HSA-804914)

Molecular Interaction Atlas (MIA) of This DOT

9 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 6 (SLC27A6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Long-chain fatty acid transport protein 6 (SLC27A6).	[10]

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 Long-chain fatty acid transport protein 6 (SLC27A6).	[8]

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] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] 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.
• [10] 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.