Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8RGNH8)

• DOT Name: ATP-binding cassette sub-family D member 2 (ABCD2)
• Synonyms: EC 3.1.2.-; EC 7.6.2.-; Adrenoleukodystrophy-like 1; Adrenoleukodystrophy-related protein; hALDR
• Gene Name: ABCD2
• UniProt ID: ABCD2_HUMAN
• EC Number: 3.1.2.-; 7.6.2.-
• Pfam ID: PF06472 ; PF00005
• Sequence:
  MTHMLNAAADRVKWTRSSAAKRAACLVAAAYALKTLYPIIGKRLKQSGHGKKKAAAYPAA
  ENTEILHCTETICEKPSPGVNADFFKQLLELRKILFPKLVTTETGWLCLHSVALISRTFL
  SIYVAGLDGKIVKSIVEKKPRTFIIKLIKWLMIAIPATFVNSAIRYLECKLALAFRTRLV
  DHAYETYFTNQTYYKVINMDGRLANPDQSLTEDIMMFSQSVAHLYSNLTKPILDVMLTSY
  TLIQTATSRGASPIGPTLLAGLVVYATAKVLKACSPKFGKLVAEEAHRKGYLRYVHSRII
  ANVEEIAFYRGHKVEMKQLQKSYKALADQMNLILSKRLWYIMIEQFLMKYVWSSSGLIMV
  AIPIITATGFADGEDGQKQVMVSERTEAFTTARNLLASGADAIERIMSSYKEVTELAGYT
  ARVYNMFWVFDEVKRGIYKRTAVIQESESHSKNGAKVELPLSDTLAIKGKVIDVDHGIIC
  ENVPIITPAGEVVASRLNFKVEEGMHLLITGPNGCGKSSLFRILSGLWPVYEGVLYKPPP
  QHMFYIPQRPYMSLGSLRDQVIYPDSVDDMHDKGYTDQDLERILHNVHLYHIVQREGGWD
  AVMDWKDVLSGGEKQRMGMARMFYHKPKYALLDECTSAVSIDVEGKIFQAAKGAGISLLS
  ITHRPSLWKYHTHLLQFDGEGGWRFEQLDTAIRLTLSEEKQKLESQLAGIPKMQQRLNEL
  CKILGEDSVLKTIKNEDETS
• Function: ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen. Like ABCD1 seems to have fatty acyl-CoA thioesterase (ACOT) and ATPase activities, according to this model, VLCFA-CoA as free VLCFA is transpoted in an ATP-dependent manner into peroxisomes after the hydrolysis of VLCFA-CoA mediated by the ACOT activity of ABCD2 (Probable). Shows overlapping substrate specificities with ABCD1 toward saturated fatty acids (FA) and monounsaturated FA (MUFA) but has a distinct substrate preference for shorter VLCFA (C22:0) and polyunsaturated fatty acid (PUFA) such as C22:6-CoA and C24:6-CoA (in vitro). Thus, may play a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation.
• Tissue Specificity: Predominantly expressed in brain and heart.
• KEGG Pathway:
  ABC transporters (hsa02010)
  Peroxisome (hsa04146)
• Reactome Pathway:
  Class I peroxisomal membrane protein import (R-HSA-9603798)
  ABC transporters in lipid homeostasis (R-HSA-1369062)

Molecular Interaction Atlas (MIA) of This DOT

3 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 ATP-binding cassette sub-family D member 2 (ABCD2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP-binding cassette sub-family D member 2 (ABCD2).	[2]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of ATP-binding cassette sub-family D member 2 (ABCD2).	[3]

2 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 ATP-binding cassette sub-family D member 2 (ABCD2).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ATP-binding cassette sub-family D member 2 (ABCD2).	[5]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [4] 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.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.