Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6Q079J)

• DOT Name: ATP-binding cassette sub-family F member 1 (ABCF1)
• Synonyms: ATP-binding cassette 50; TNF-alpha-stimulated ABC protein
• Gene Name: ABCF1
• Related Disease:
  Advanced cancer
  Arthritis
  Hepatocellular carcinoma
  Acute intermittent hepatic porphyria
  Allergy
  Breast carcinoma
  Colorectal carcinoma
  Graves disease
  Lung adenocarcinoma
  Myasthenia gravis
  Pancreatitis
  Pneumonia
  Pneumonitis
  Rheumatoid arthritis
  Schizophrenia
  Type-1 diabetes
  Lung cancer
  Systemic lupus erythematosus
• UniProt ID: ABCF1_HUMAN
• PDB ID: 5ZXD
• Pfam ID: PF00005
• Sequence:
  MPKAPKQQPPEPEWIGDGESTSPSDKVVKKGKKDKKIKKTFFEELAVEDKQAGEEEKVLK
  EKEQQQQQQQQQQKKKRDTRKGRRKKDVDDDGEEKELMERLKKLSVPTSDEEDEVPAPKP
  RGGKKTKGGNVFAALIQDQSEEEEEEEKHPPKPAKPEKNRINKAVSEEQQPALKGKKGKE
  EKSKGKAKPQNKFAALDNEEEDKEEEIIKEKEPPKQGKEKAKKAEQGSEEEGEGEEEEEE
  GGESKADDPYAHLSKKEKKKLKKQMEYERQVASLKAANAAENDFSVSQAEMSSRQAMLEN
  ASDIKLEKFSISAHGKELFVNADLYIVAGRRYGLVGPNGKGKTTLLKHIANRALSIPPNI
  DVLLCEQEVVADETPAVQAVLRADTKRLKLLEEERRLQGQLEQGDDTAAERLEKVYEELR
  ATGAAAAEAKARRILAGLGFDPEMQNRPTQKFSGGWRMRVSLARALFMEPTLLMLDEPTN
  HLDLNAVIWLNNYLQGWRKTLLIVSHDQGFLDDVCTDIIHLDAQRLHYYRGNYMTFKKMY
  QQKQKELLKQYEKQEKKLKELKAGGKSTKQAEKQTKEALTRKQQKCRRKNQDEESQEAPE
  LLKRPKEYTVRFTFPDPPPLSPPVLGLHGVTFGYQGQKPLFKNLDFGIDMDSRICIVGPN
  GVGKSTLLLLLTGKLTPTHGEMRKNHRLKIGFFNQQYAEQLRMEETPTEYLQRGFNLPYQ
  DARKCLGRFGLESHAHTIQICKLSGGQKARVVFAELACREPDVLILDEPTNNLDIESIDA
  LGEAINEYKGAVIVVSHDARLITETNCQLWVVEEQSVSQIDGDFEDYKREVLEALGEVMV
  SRPRE
• Function: Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: ABC-family proteins mediated transport (R-HSA-382556)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Arthritis	DIST1YEL	Definitive	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Acute intermittent hepatic porphyria	DIS80J7E	Strong	Biomarker	[3]
Allergy	DIS48ZAP	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[7]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[8]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[9]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[3]
Pneumonia	DIS8EF3M	Strong	Biomarker	[4]
Pneumonitis	DIS88E0K	Strong	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[10]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[11]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[13]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-binding cassette sub-family F member 1 (ABCF1).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ATP-binding cassette sub-family F member 1 (ABCF1).	[16]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of ATP-binding cassette sub-family F member 1 (ABCF1).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of ATP-binding cassette sub-family F member 1 (ABCF1).	[21]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of ATP-binding cassette sub-family F member 1 (ABCF1).	[22]

5 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 decreases the methylation of ATP-binding cassette sub-family F member 1 (ABCF1).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of ATP-binding cassette sub-family F member 1 (ABCF1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ATP-binding cassette sub-family F member 1 (ABCF1).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of ATP-binding cassette sub-family F member 1 (ABCF1).	[19]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of ATP-binding cassette sub-family F member 1 (ABCF1).	[23]

References

• [1] The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma.Cancer Lett. 2019 Aug 10;457:98-109. doi: 10.1016/j.canlet.2019.05.010. Epub 2019 May 14.
• [2] The role of the innate immune response regulatory gene ABCF1 in mammalian embryogenesis and development.PLoS One. 2017 May 19;12(5):e0175918. doi: 10.1371/journal.pone.0175918. eCollection 2017.
• [3] Two critical genes (HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis.Immunogenetics. 2007 Jan;59(1):45-52. doi: 10.1007/s00251-006-0178-2. Epub 2006 Nov 21.
• [4] Expansion of CD4(+) CD25(+) and CD25(-) T-Bet, GATA-3, Foxp3 and RORt cells in allergic inflammation, local lung distribution and chemokine gene expression.PLoS One. 2011;6(5):e19889. doi: 10.1371/journal.pone.0019889. Epub 2011 May 19.
• [5] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [6] Elevated microRNA-23a Expression Enhances the Chemoresistance of Colorectal Cancer Cells with Microsatellite Instability to 5-Fluorouracil by Directly Targeting ABCF1.Curr Protein Pept Sci. 2015;16(4):301-9. doi: 10.2174/138920371604150429153309.
• [7] Single nucleotide polymorphisms at the PRR3, ABCF1, and GNL1 genes in the HLA class I region are associated with Graves' ophthalmopathy in a gender-dependent manner.Ophthalmology. 2014 Oct;121(10):2033-9. doi: 10.1016/j.ophtha.2014.04.027. Epub 2014 Jun 5.
• [8] A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.Am J Hum Genet. 2009 Nov;85(5):679-91. doi: 10.1016/j.ajhg.2009.09.012. Epub 2009 Oct 15.
• [9] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [10] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [11] A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.PLoS One. 2012;7(6):e39498. doi: 10.1371/journal.pone.0039498. Epub 2012 Jun 27.
• [12] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [13] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [14] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [15] 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.
• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [17] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [18] 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.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] 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.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [23] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.