Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4OK511)

DOT Name Long-chain fatty acid transport protein 5 (SLC27A5)
Synonyms
FATP-5; Fatty acid transport protein 5; Bile acid-CoA ligase; BA-CoA ligase; BAL; Bile acyl-CoA synthetase; BACS; EC 6.2.1.7; Cholate--CoA ligase; Fatty-acid-coenzyme A ligase, very long-chain 3; Long-chain-fatty-acid--CoA ligase; EC 6.2.1.3; Solute carrier family 27 member 5; Very long-chain acyl-CoA synthetase homolog 2; VLCS-H2; VLCSH2; EC 6.2.1.-; Very long-chain acyl-CoA synthetase-related protein; VLACS-related; VLACSR
Gene Name SLC27A5
UniProt ID
S27A5_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.-; 6.2.1.3; 6.2.1.7
Pfam ID
PF00501 ; PF13193
Sequence
MGVRQQLALLLLLLLLLWGLGQPVWPVAVALTLRWLLGDPTCCVLLGLAMLARPWLGPWV
PHGLSLAAAALALTLLPARLPPGLRWLPADVIFLAKILHLGLKIRGCLSRQPPDTFVDAF
ERRARAQPGRALLVWTGPGAGSVTFGELDARACQAAWALKAELGDPASLCAGEPTALLVL
ASQAVPALCMWLGLAKLGCPTAWINPHGRGMPLAHSVLSSGARVLVVDPDLRESLEEILP
KLQAENIRCFYLSHTSPTPGVGALGAALDAAPSHPVPADLRAGITWRSPALFIYTSGTTG
LPKPAILTHERVLQMSKMLSLSGATADDVVYTVLPLYHVMGLVVGILGCLDLGATCVLAP
KFSTSCFWDDCRQHGVTVILYVGELLRYLCNIPQQPEDRTHTVRLAMGNGLRADVWETFQ
QRFGPIRIWEVYGSTEGNMGLVNYVGRCGALGKMSCLLRMLSPFELVQFDMEAAEPVRDN
QGFCIPVGLGEPGLLLTKVVSQQPFVGYRGPRELSERKLVRNVRQSGDVYYNTGDVLAMD
REGFLYFRDRLGDTFRWKGENVSTHEVEGVLSQVDFLQQVNVYGVCVPGCEGKVGMAAVQ
LAPGQTFDGEKLYQHVRAWLPAYATPHFIRIQDAMEVTSTFKLMKTRLVREGFNVGIVVD
PLFVLDNRAQSFRPLTAEMYQAVCEGTWRL
Function
May mediate the import of long-chain fatty acids (LCFA) by facilitating their transport across cell membranes. Also catalyzes the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates. Mainly functions as a bile acyl-CoA synthetase catalyzing the activation of bile acids via ATP-dependent formation of bile acid CoA thioesters which is necessary for their subsequent conjugation with glycine or taurine. Both primary bile acids (cholic acid and chenodeoxycholic acid) and secondary bile acids (deoxycholic acid and lithocholic acid) are the principal substrates. In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate ((25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate or THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. Plays an important role in hepatic fatty acid uptake and bile acid reconjugation and recycling but not in de novo synthesis of bile acids.
Tissue Specificity Predominantly expressed in liver.
KEGG Pathway
Primary bile acid biosynthesis (hsa00120 )
Metabolic pathways (hsa01100 )
PPAR sig.ling pathway (hsa03320 )
Insulin resistance (hsa04931 )
Bile secretion (hsa04976 )
Reactome Pathway
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368 )
Synthesis of bile acids and bile salts via 24-hydroxycholesterol (R-HSA-193775 )
Recycling of bile acids and salts (R-HSA-159418 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 5 (SLC27A5). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [5]
Obeticholic acid DM3Q1SM Approved Obeticholic acid decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [6]
Rifampicin DM5DSFZ Approved Rifampicin increases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [7]
Mifepristone DMGZQEF Approved Mifepristone decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [8]
Olanzapine DMPFN6Y Approved Olanzapine increases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [9]
Berberine DMC5Q8X Phase 4 Berberine decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [2]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Long-chain fatty acid transport protein 5 (SLC27A5). [11]
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⏷ Show the Full List of 12 Drug(s)

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 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 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
7 Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
8 Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
9 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.
10 Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice. Toxicol Appl Pharmacol. 2017 Feb 1;316:74-82. doi: 10.1016/j.taap.2016.12.019. Epub 2016 Dec 28.
11 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.