Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUU40U3)

• DOT Name: Melanoma-associated antigen F1 (MAGEF1)
• Synonyms: MAGE-F1; MAGE-F1 antigen
• Gene Name: MAGEF1
• Related Disease:
  Advanced cancer
  leukaemia
  Leukemia
  Neoplasm
  Breast cancer
  Breast carcinoma
• UniProt ID: MAGF1_HUMAN
• Pfam ID: PF01454
• Sequence:
  MLQTPESRGLPVPQAEGEKDGGHDGETRAPTASQERPKEELGAGREEGAAEPALTRKGAR
  ALAAKALARRRAYRRLNRTVAELVQFLLVKDKKKSPITRSEMVKYVIGDLKILFPDIIAR
  AAEHLRYVFGFELKQFDRKHHTYILINKLKPLEEEEEEDLGGDGPRLGLLMMILGLIYMR
  GNSAREAQVWEMLRRLGVQPSKYHFLFGYPKRLIMEDFVQQRYLSYRRVPHTNPPEYEFS
  WGPRSNLEISKMEVLGFVAKLHKKEPQHWPVQYREALADEADRARAKARAEASMRARASA
  RAGIHLW
• Function: Enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin ligases. Proposed to act through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. MAGEF1-NSMCE1 ubiquitin ligase complex promotes proteasomal degradation of MMS19, a key component of the cytosolic iron-sulfur protein assembly (CIA) machinery. Down-regulation of MMS19 impairs the activity of several DNA repair and metabolism enzymes such as ERCC2/XPD, FANCJ, RTEL1 and POLD1 that require iron-sulfur clusters as cofactors. May negatively regulate genome integrity by inhibiting homologous recombination-mediated double-strand break DNA repair.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[3]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Melanoma-associated antigen F1 (MAGEF1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Melanoma-associated antigen F1 (MAGEF1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Melanoma-associated antigen F1 (MAGEF1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Melanoma-associated antigen F1 (MAGEF1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Melanoma-associated antigen F1 (MAGEF1).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Melanoma-associated antigen F1 (MAGEF1).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Melanoma-associated antigen F1 (MAGEF1).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Melanoma-associated antigen F1 (MAGEF1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Melanoma-associated antigen F1 (MAGEF1).	[12]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Melanoma-associated antigen F1 (MAGEF1).	[13]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Melanoma-associated antigen F1 (MAGEF1).	[16]

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 Melanoma-associated antigen F1 (MAGEF1).	[14]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Melanoma-associated antigen F1 (MAGEF1).	[15]

References

• [1] Cytosolic Iron-Sulfur Assembly Is Evolutionarily Tuned by a Cancer-Amplified Ubiquitin Ligase.Mol Cell. 2018 Jan 4;69(1):113-125.e6. doi: 10.1016/j.molcel.2017.11.010. Epub 2017 Dec 7.
• [2] MAGE-F1, a novel ubiquitously expressed member of the MAGE superfamily.Gene. 2001 Apr 18;267(2):173-82. doi: 10.1016/s0378-1119(01)00406-1.
• [3] Prognostic roles of MAGE family members in breast cancer based on KM-Plotter Data.Oncol Lett. 2019 Oct;18(4):3501-3516. doi: 10.3892/ol.2019.10722. Epub 2019 Aug 6.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] 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.
• [11] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [14] 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.
• [15] 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.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.