Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBK6BBM)

DOT Name E3 ubiquitin-protein ligase MARCHF5 (MARCHF5)
Synonyms
EC 2.3.2.27; Membrane-associated RING finger protein 5; Membrane-associated RING-CH protein V; MARCH-V; Mitochondrial ubiquitin ligase; MITOL; RING finger protein 153; RING-type E3 ubiquitin transferase MARCHF5
Gene Name MARCHF5
Related Disease
Parkinson disease ( )
Advanced cancer ( )
Benign prostatic hyperplasia ( )
Carcinoma of esophagus ( )
Cardiovascular disease ( )
Chronic kidney disease ( )
Epithelial ovarian cancer ( )
Esophageal cancer ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Neoplasm of esophagus ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Staphylococcus infection ( )
Tuberculosis ( )
Breast cancer ( )
Breast carcinoma ( )
Neoplasm ( )
UniProt ID
MARH5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.27
Pfam ID
PF12906
Sequence
MPDQALQQMLDRSCWVCFATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEKQRGNST
ARVACPQCNAEYLIVFPKLGPVVYVLDLADRLISKACPFAAAGIMVGSIYWTAVTYGAVT
VMQVVGHKEGLDVMERADPLFLLIGLPTIPVMLILGKMIRWEDYVLRLWRKYSNKLQILN
SIFPGIGCPVPRIPAEANPLADHVSATRILCGALVFPTIATIVGKLMFSSVNSNLQRTIL
GGIAFVAIKGAFKVYFKQQQYLRQAHRKILNYPEQEEA
Function
Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1.
Tissue Specificity Expressed in brain, heart, liver, lung, spleen, stomach, testis, skeletal and muscle.
KEGG Pathway
Mitophagy - animal (hsa04137 )

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Parkinson disease DISQVHKL Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Genetic Variation [2]
Benign prostatic hyperplasia DISI3CW2 Strong Genetic Variation [3]
Carcinoma of esophagus DISS6G4D Strong Genetic Variation [2]
Cardiovascular disease DIS2IQDX Strong Biomarker [4]
Chronic kidney disease DISW82R7 Strong Biomarker [5]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [6]
Esophageal cancer DISGB2VN Strong Genetic Variation [2]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [7]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [7]
Neoplasm of esophagus DISOLKAQ Strong Genetic Variation [2]
Ovarian cancer DISZJHAP Strong Biomarker [6]
Ovarian neoplasm DISEAFTY Strong Biomarker [6]
Staphylococcus infection DISY8WGS Strong Genetic Variation [8]
Tuberculosis DIS2YIMD Strong Genetic Variation [9]
Breast cancer DIS7DPX1 moderate Biomarker [10]
Breast carcinoma DIS2UE88 moderate Biomarker [10]
Neoplasm DISZKGEW moderate Altered Expression [10]
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⏷ Show the Full List of 18 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [11]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [12]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [13]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [14]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [15]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [17]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [18]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of E3 ubiquitin-protein ligase MARCHF5 (MARCHF5). [19]
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⏷ Show the Full List of 9 Drug(s)

References

1 Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial.JAMA Neurol. 2017 Feb 1;74(2):216-224. doi: 10.1001/jamaneurol.2016.4467.
2 Effect of ALDH2 polymorphism on cancer risk in Asians: A meta-analysis.Medicine (Baltimore). 2019 Mar;98(13):e14855. doi: 10.1097/MD.0000000000014855.
3 Meta-analysis of vitamin D receptor gene polymorphisms and benign prostatic hyperplasia risk.Mol Biol Rep. 2014 Oct;41(10):6713-7. doi: 10.1007/s11033-014-3554-2. Epub 2014 Jul 3.
4 Mitochondrial Ubiquitin Ligase in Cardiovascular Disorders.Adv Exp Med Biol. 2017;982:327-333. doi: 10.1007/978-3-319-55330-6_17.
5 Effect of diet protein restriction on progression of chronic kidney disease: A systematic review and meta-analysis.PLoS One. 2018 Nov 7;13(11):e0206134. doi: 10.1371/journal.pone.0206134. eCollection 2018.
6 MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells.Autophagy. 2017 Feb;13(2):333-344. doi: 10.1080/15548627.2016.1256520. Epub 2016 Nov 22.
7 Mitochondria ubiquitin ligase, MARCH5 resolves hepatitis B virus X protein aggregates in the liver pathogenesis.Cell Death Dis. 2019 Dec 9;10(12):938. doi: 10.1038/s41419-019-2175-z.
8 Control of MSSA and MRSA in the United States: protocols, policies, risk adjustment and excuses.Antimicrob Resist Infect Control. 2019 Jun 19;8:103. doi: 10.1186/s13756-019-0550-2. eCollection 2019.
9 Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study.PLoS Med. 2019 Apr 16;16(4):e1002781. doi: 10.1371/journal.pmed.1002781. eCollection 2019 Apr.
10 MARCH5 overexpression contributes to tumor growth and metastasis and associates with poor survival in breast cancer.Cancer Manag Res. 2018 Dec 24;11:201-215. doi: 10.2147/CMAR.S190694. eCollection 2019.
11 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
12 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
13 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
14 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
18 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
19 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.