Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT05NF37)

• DOT Name: Interferon-induced GTP-binding protein Mx2 (MX2)
• Synonyms: Interferon-regulated resistance GTP-binding protein MxB; Myxovirus resistance protein 2; p78-related protein
• Gene Name: MX2
• Related Disease:
  Cutaneous melanoma
  Lung adenocarcinoma
  Influenza
  Narcolepsy
  Parkinson disease
  Melanoma
  Glioblastoma multiforme
  Tourette syndrome
• UniProt ID: MX2_HUMAN
• PDB ID: 4WHJ; 4X0R; 5UOT
• Pfam ID: PF01031 ; PF00350 ; PF02212
• Sequence:
  MSKAHKPWPYRRRSQFSSRKYLKKEMNSFQQQPPPFGTVPPQMMFPPNWQGAEKDAAFLA
  KDFNFLTLNNQPPPGNRSQPRAMGPENNLYSQYEQKVRPCIDLIDSLRALGVEQDLALPA
  IAVIGDQSSGKSSVLEALSGVALPRGSGIVTRCPLVLKLKKQPCEAWAGRISYRNTELEL
  QDPGQVEKEIHKAQNVMAGNGRGISHELISLEITSPEVPDLTIIDLPGITRVAVDNQPRD
  IGLQIKALIKKYIQRQQTINLVVVPCNVDIATTEALSMAHEVDPEGDRTIGILTKPDLMD
  RGTEKSVMNVVRNLTYPLKKGYMIVKCRGQQEITNRLSLAEATKKEITFFQTHPYFRVLL
  EEGSATVPRLAERLTTELIMHIQKSLPLLEGQIRESHQKATEELRRCGADIPSQEADKMF
  FLIEKIKMFNQDIEKLVEGEEVVRENETRLYNKIREDFKNWVGILATNTQKVKNIIHEEV
  EKYEKQYRGKELLGFVNYKTFEIIVHQYIQQLVEPALSMLQKAMEIIQQAFINVAKKHFG
  EFFNLNQTVQSTIEDIKVKHTAKAENMIQLQFRMEQMVFCQDQIYSVVLKKVREEIFNPL
  GTPSQNMKLNSHFPSNESSVSSFTEIGIHLNAYFLETSKRLANQIPFIIQYFMLRENGDS
  LQKAMMQILQEKNRYSWLLQEQSETATKRRILKERIYRLTQARHALCQFSSKEIH
• Function: Interferon-induced dynamin-like GTPase with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1). Acts by targeting the viral capsid and affects the nuclear uptake and/or stability of the HIV-1 replication complex and the subsequent chromosomal integration of the proviral DNA. Exhibits antiviral activity also against simian immunodeficiency virus (SIV-mnd). May play a role in regulating nucleocytoplasmic transport and cell-cycle progression.
• KEGG Pathway:
  Viral life cycle - HIV-1 (hsa03250)
  Hepatitis C (hsa05160)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[2]
Influenza	DIS3PNU3	Strong	Biomarker	[3]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[4]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[5]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[6]
Glioblastoma multiforme	DISK8246	Limited	Genetic Variation	[7]
Tourette syndrome	DISX9D54	No Known	Unknown	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Interferon-induced GTP-binding protein Mx2 (MX2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[16]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[17]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[18]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[19]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[20]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[22]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon-induced GTP-binding protein Mx2 (MX2).	[26]

References

• [1] Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.Nat Commun. 2018 Nov 14;9(1):4774. doi: 10.1038/s41467-018-06649-5.
• [2] Identification of genes whose expression is upregulated in lung adenocarcinoma cells in comparison with type II alveolar cells and bronchiolar epithelial cells in vivo.Oncogene. 2004 Apr 15;23(17):3089-96. doi: 10.1038/sj.onc.1207433.
• [3] A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
• [4] MX2 gene expression tends to be downregulated in subjects with HLA-DQB1*0602.Sleep. 2008 May;31(5):749-51. doi: 10.1093/sleep/31.5.749.
• [5] PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease.Neurology. 2015 Mar 10;84(10):972-80. doi: 10.1212/WNL.0000000000001332. Epub 2015 Feb 6.
• [6] MX 2 is a novel regulator of cell cycle in melanoma cells.Pigment Cell Melanoma Res. 2020 May;33(3):446-457. doi: 10.1111/pcmr.12837. Epub 2019 Nov 13.
• [7] Overexpression of human MX2 gene suppresses cell proliferation, migration, and invasion via ERK/P38/NF-B pathway in glioblastoma cells.J Cell Biochem. 2019 Nov;120(11):18762-18770. doi: 10.1002/jcb.29189. Epub 2019 Jul 2.
• [8] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] 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.
• [11] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [14] 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.
• [15] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [16] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [17] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [18] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [19] 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.
• [20] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [21] White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nat Cell Biol. 2015 Jan;17(1):57-67. doi: 10.1038/ncb3075. Epub 2014 Dec 8.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [24] 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.
• [25] Global gene expression analysis reveals novel transcription factors associated with long-term low-level exposure of EA.hy926 human endothelial cells to bisphenol A. Chem Biol Interact. 2023 Aug 25;381:110571. doi: 10.1016/j.cbi.2023.110571. Epub 2023 May 25.
• [26] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.