Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDNRW37)

• DOT Name: Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B)
• Synonyms: CPT1-M; EC 2.3.1.21; Carnitine O-palmitoyltransferase I, muscle isoform; CPT I; CPTI-M; Carnitine palmitoyltransferase 1B; Carnitine palmitoyltransferase I-like protein
• Gene Name: CPT1B
• Related Disease: Inherited fatty acid metabolism disorder
• UniProt ID: CPT1B_HUMAN
• EC Number: 2.3.1.21
• Pfam ID: PF00755 ; PF16484
• Sequence:
  MAEAHQAVAFQFTVTPDGVDFRLSREALKHVYLSGINSWKKRLIRIKNGILRGVYPGSPT
  SWLVVIMATVGSSFCNVDISLGLVSCIQRCLPQGCGPYQTPQTRALLSMAIFSTGVWVTG
  IFFFRQTLKLLLCYHGWMFEMHGKTSNLTRIWAMCIRLLSSRHPMLYSFQTSLPKLPVPR
  VSATIQRYLESVRPLLDDEEYYRMELLAKEFQDKTAPRLQKYLVLKSWWASNYVSDWWEE
  YIYLRGRSPLMVNSNYYVMDLVLIKNTDVQAARLGNIIHAMIMYRRKLDREEIKPVMALG
  IVPMCSYQMERMFNTTRIPGKDTDVLQHLSDSRHVAVYHKGRFFKLWLYEGARLLKPQDL
  EMQFQRILDDPSPPQPGEEKLAALTAGGRVEWAQARQAFFSSGKNKAALEAIERAAFFVA
  LDEESYSYDPEDEASLSLYGKALLHGNCYNRWFDKSFTLISFKNGQLGLNAEHAWADAPI
  IGHLWEFVLGTDSFHLGYTETGHCLGKPNPALAPPTRLQWDIPKQCQAVIESSYQVAKAL
  ADDVELYCFQFLPFGKGLIKKCRTSPDAFVQIALQLAHFRDRGKFCLTYEASMTRMFREG
  RTETVRSCTSESTAFVQAMMEGSHTKADLRDLFQKAAKKHQNMYRLAMTGAGIDRHLFCL
  YLVSKYLGVSSPFLAEVLSEPWRLSTSQIPQSQIRMFDPEQHPNHLGAGGGFGPVADDGY
  GVSYMIAGENTIFFHISSKFSSSETNAQRFGNHIRKALLDIADLFQVPKAYS
• Function: Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion.
• Tissue Specificity: Strong expression in heart and skeletal muscle. No expression in liver and kidney.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  Efferocytosis (hsa04148)
  AMPK sig.ling pathway (hsa04152)
  Thermogenesis (hsa04714)
  Adipocytokine sig.ling pathway (hsa04920)
  Glucagon sig.ling pathway (hsa04922)
  Insulin resistance (hsa04931)
  Alcoholic liver disease (hsa04936)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Signaling by Retinoic Acid (R-HSA-5362517)
  Carnitine metabolism (R-HSA-200425)
• BioCyc Pathway: MetaCyc:MONOMER66-34409

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inherited fatty acid metabolism disorder	DISOT51Y	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[6]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[2]

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 affects the methylation of Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1B).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.
• [5] 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.
• [6] 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.
• [7] Differential effects of peroxisome proliferator-activated receptor activators on the mRNA levels of genes involved in lipid metabolism in primary human monocyte-derived macrophages. Metabolism. 2003 May;52(5):652-7. doi: 10.1053/meta.2003.50100.
• [8] Rosiglitazone-Mediated Effects on Skeletal Muscle Gene Expression Correlate with Improvements in Insulin Sensitivity in Individuals with HIV-Insulin Resistance. Patholog Res Int. 2011 Apr 12;2011:736425. doi: 10.4061/2011/736425.
• [9] 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.
• [10] 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.