Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXIBZ3N)

• DOT Name: ATP-binding cassette sub-family F member 2 (ABCF2)
• Synonyms: Iron-inhibited ABC transporter 2
• Gene Name: ABCF2
• Related Disease:
  Advanced cancer
  Cervical cancer
  Cervical carcinoma
  Chorioamnionitis
  Endometrial cancer
  Endometrial carcinoma
  Hepatocellular carcinoma
  Malignant uterine tumour
  Adenocarcinoma
  Clear cell adenocarcinoma
• UniProt ID: ABCF2_HUMAN
• Pfam ID: PF00005 ; PF12848
• Sequence:
  MPSDLAKKKAAKKKEAAKARQRPRKGHEENGDVVTEPQVAEKNEANGRETTEVDLLTKEL
  EDFEMKKAAARAVTGVLASHPNSTDVHIINLSLTFHGQELLSDTKLELNSGRRYGLIGLN
  GIGKSMLLSAIGKREVPIPEHIDIYHLTREMPPSDKTPLHCVMEVDTERAMLEKEAERLA
  HEDAECEKLMELYERLEELDADKAEMRASRILHGLGFTPAMQRKKLKDFSGGWRMRVALA
  RALFIRPFMLLLDEPTNHLDLDACVWLEEELKTFKRILVLVSHSQDFLNGVCTNIIHMHN
  KKLKYYTGNYDQYVKTRLELEENQMKRFHWEQDQIAHMKNYIARFGHGSAKLARQAQSKE
  KTLQKMMASGLTERVVSDKTLSFYFPPCGKIPPPVIMVQNVSFKYTKDGPCIYNNLEFGI
  DLDTRVALVGPNGAGKSTLLKLLTGELLPTDGMIRKHSHVKIGRYHQHLQEQLDLDLSPL
  EYMMKCYPEIKEKEEMRKIIGRYGLTGKQQVSPIRNLSDGQKCRVCLAWLAWQNPHMLFL
  DEPTNHLDIETIDALADAINEFEGGMMLVSHDFRLIQQVAQEIWVCEKQTITKWPGDILA
  YKEHLKSKLVDEEPQLTKRTHNV
• KEGG Pathway: Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway: NFE2L2 regulating MDR associated enzymes (R-HSA-9818032)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[1]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[1]
Chorioamnionitis	DISL1D9U	Strong	Altered Expression	[2]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[1]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Malignant uterine tumour	DIS3QDT8	Strong	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[4]
Clear cell adenocarcinoma	DISYUGHZ	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[13]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[18]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of ATP-binding cassette sub-family F member 2 (ABCF2).	[19]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ATP-binding cassette sub-family F member 2 (ABCF2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ATP-binding cassette sub-family F member 2 (ABCF2).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of ATP-binding cassette sub-family F member 2 (ABCF2).	[16]

References

• [1] Can ABCF2 protein expression predict the prognosis of uterine cancer?.Br J Cancer. 2008 Nov 18;99(10):1651-5. doi: 10.1038/sj.bjc.6604734.
• [2] Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta.Cell Physiol Biochem. 2018;45(2):591-604. doi: 10.1159/000487100. Epub 2018 Jan 29.
• [3] Circ-TCF4.85 silencing inhibits cancer progression through microRNA-486-5p-targeted inhibition of ABCF2 in hepatocellular carcinoma.Mol Oncol. 2020 Feb;14(2):447-461. doi: 10.1002/1878-0261.12603. Epub 2020 Jan 10.
• [4] Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses.Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6880-8. doi: 10.1158/1078-0432.CCR-05-0751.
• [5] Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs.Hum Pathol. 2007 Jan;38(1):134-9. doi: 10.1016/j.humpath.2006.06.026. Epub 2006 Sep 25.
• [6] 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.
• [7] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [8] 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.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [15] 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.
• [16] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [17] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.