Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH7PNN2)

DOT Name E3 ubiquitin-protein ligase MARCHF8 (MARCHF8)
Synonyms
EC 2.3.2.27; Cellular modulator of immune recognition; c-MIR; Membrane-associated RING finger protein 8; Membrane-associated RING-CH protein VIII; MARCH-VIII; RING finger protein 178; RING-type E3 ubiquitin transferase MARCHF8
Gene Name MARCHF8
Related Disease
Prostate carcinoma ( )
B-cell lymphoma ( )
B-cell neoplasm ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of esophagus ( )
Cardiomyopathy ( )
Cervical cancer ( )
Cervical carcinoma ( )
Clear cell renal carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal cancer ( )
Esophageal squamous cell carcinoma ( )
Ewing sarcoma ( )
Follicular lymphoma ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Huntington disease ( )
leukaemia ( )
Liver cirrhosis ( )
Lung cancer ( )
Neoplasm ( )
Neoplasm of esophagus ( )
Non-alcoholic fatty liver disease ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
Plasma cell myeloma ( )
Prostate cancer ( )
Renal cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Vascular disease ( )
Chronic hepatitis B virus infection ( )
Chronic obstructive pulmonary disease ( )
Lung carcinoma ( )
Obesity ( )
Osteoarthritis ( )
Small lymphocytic lymphoma ( )
Advanced cancer ( )
Gastric cancer ( )
Hereditary breast carcinoma ( )
Metastatic malignant neoplasm ( )
Non-insulin dependent diabetes ( )
Stomach cancer ( )
UniProt ID
MARH8_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2D8S
EC Number
2.3.2.27
Pfam ID
PF12906
Sequence
MSMPLHQISAIPSQDAISARVYRSKTKEKEREEQNEKTLGHFMSHSSNISKAGSPPSASA
PAPVSSFSRTSITPSSQDICRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDT
RCCELCKYEFIMETKLKPLRKWEKLQMTSSERRKIMCSVTFHVIAITCVVWSLYVLIDRT
AEEIKQGQATGILEWPFWTKLVVVAIGFTGGLLFMYVQCKVYVQLWKRLKAYNRVIYVQN
CPETSKKNIFEKSPLTEPNFENKHGYGICHSDTNSSCCTEPEDTGAEIIHV
Function
E3 ubiquitin-protein ligase that plays several important roles in innate immunity and adaptive immunity. Mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. Possesses a very broad antiviral activity by specifically inactivating different viral fusion proteins. Targets and ubiquitinates cytoplasmic lysine residues of viral envelope glycoproteins with single transmembrane domains leading to their lysosomal degradation. Therefore, shows broad-spectrum inhibition against many viruses including retroviruses, rhabdoviruses, arenaviruses, sarbecoviruses or influenzaviruses. Strongly blocks human immunodeficiency virus type 1 envelope glycoprotein incorporation into virions by down-regulating its cell surface expression. Blocks also ebola virus glycoprotein/GP incorporation via surface down-regulation. Mediates 'Lys-63'-linked polyubiquitination of influenza M2 to target it to lysosome for degradation. Mediates the regulation of constitutive ubiquitination and trafficking of the viral restriction factor BST2 within the endocytic pathway. Plays a role in maintenance of immune tolerance to self by promoting the turnover and proteasomal degradation of PD-L1/CD274 via ubiquitination. Catalyzes the 'Lys-63'-linked polyubiquitylation of cGAS thereby inhibiting its DNA binding ability and impairing its antiviral innate immunity ; (Microbial infection) Mediates 'Lys-63'-linked polyubiquitination of hepatitis C virus/HCV protein NS2 which allows its binding to HGS, an ESCRT-0 complex component, and this interaction is essential for HCV envelopment.
Tissue Specificity Broadly expressed. Present in immature dendritic cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Prostate carcinoma DISMJPLE Definitive Biomarker [1]
B-cell lymphoma DISIH1YQ Strong Altered Expression [2]
B-cell neoplasm DISVY326 Strong Genetic Variation [3]
Bladder cancer DISUHNM0 Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Genetic Variation [5]
Breast carcinoma DIS2UE88 Strong Genetic Variation [5]
Carcinoma of esophagus DISS6G4D Strong Biomarker [6]
Cardiomyopathy DISUPZRG Strong Genetic Variation [7]
Cervical cancer DISFSHPF Strong Genetic Variation [8]
Cervical carcinoma DIST4S00 Strong Genetic Variation [8]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [9]
Endometrial cancer DISW0LMR Strong Genetic Variation [10]
Endometrial carcinoma DISXR5CY Strong Genetic Variation [10]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [11]
Esophageal cancer DISGB2VN Strong Biomarker [6]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [6]
Ewing sarcoma DISQYLV3 Strong Biomarker [12]
Follicular lymphoma DISVEUR6 Strong Altered Expression [2]
Glioma DIS5RPEH Strong Biomarker [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [14]
Hepatocellular carcinoma DIS0J828 Strong Genetic Variation [15]
High blood pressure DISY2OHH Strong Genetic Variation [16]
Huntington disease DISQPLA4 Strong Biomarker [17]
leukaemia DISS7D1V Strong Genetic Variation [18]
Liver cirrhosis DIS4G1GX Strong Biomarker [19]
Lung cancer DISCM4YA Strong Biomarker [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Neoplasm of esophagus DISOLKAQ Strong Biomarker [6]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [22]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [23]
Pancreatic cancer DISJC981 Strong Genetic Variation [24]
Plasma cell myeloma DIS0DFZ0 Strong Biomarker [3]
Prostate cancer DISF190Y Strong Biomarker [1]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [9]
Urinary bladder cancer DISDV4T7 Strong Biomarker [4]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [4]
Vascular disease DISVS67S Strong Genetic Variation [16]
Chronic hepatitis B virus infection DISHL4NT moderate Genetic Variation [25]
Chronic obstructive pulmonary disease DISQCIRF moderate Genetic Variation [26]
Lung carcinoma DISTR26C moderate Altered Expression [27]
Obesity DIS47Y1K moderate Biomarker [28]
Osteoarthritis DIS05URM moderate Biomarker [29]
Small lymphocytic lymphoma DIS30POX moderate Altered Expression [30]
Advanced cancer DISAT1Z9 Limited Biomarker [31]
Gastric cancer DISXGOUK Limited Biomarker [32]
Hereditary breast carcinoma DISAEZT5 Limited Genetic Variation [33]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [34]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [35]
Stomach cancer DISKIJSX Limited Biomarker [32]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [36]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [37]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [38]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [41]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [42]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [43]
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⏷ Show the Full List of 6 Drug(s)
2 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 E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of E3 ubiquitin-protein ligase MARCHF8 (MARCHF8). [40]
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References

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4 MicroRNA-101 inhibits cell migration and invasion in bladder cancer via targeting FZD4.Exp Ther Med. 2019 Feb;17(2):1476-1485. doi: 10.3892/etm.2018.7084. Epub 2018 Dec 11.
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10 Genotype misclassification in genetic association studies of the rs1042522 TP53 (Arg72Pro) polymorphism: a systematic review of studies of breast, lung, colorectal, ovarian, and endometrial cancer.Am J Epidemiol. 2013 Jun 15;177(12):1317-25. doi: 10.1093/aje/kws394. Epub 2013 May 31.
11 MIR-92 stimulates VEGF by inhibiting von Hippel-Lindau gene product in epithelial ovarian cancer.J Biol Regul Homeost Agents. 2017 Jul-Sep,;31(3):615-624.
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17 Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease.Hum Mol Genet. 2011 Jun 1;20(11):2225-37. doi: 10.1093/hmg/ddr111. Epub 2011 Mar 19.
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19 Mid-infrared spectroscopy of serum, a promising non-invasive method to assess prognosis in patients with ascites and cirrhosis.PLoS One. 2017 Oct 11;12(10):e0185997. doi: 10.1371/journal.pone.0185997. eCollection 2017.
20 MARCH8 is associated with poor prognosis in non-small cell lung cancers patients.Oncotarget. 2017 Nov 21;8(64):108238-108248. doi: 10.18632/oncotarget.22602. eCollection 2017 Dec 8.
21 Overexpression of miR-199a-5p decreases esophageal cancer cell proliferation through repression of mitogen-activated protein kinase kinase kinase-11 (MAP3K11).Oncotarget. 2016 Feb 23;7(8):8756-70. doi: 10.18632/oncotarget.6752.
22 miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression.Gut. 2018 Jun;67(6):1124-1134. doi: 10.1136/gutjnl-2016-312869. Epub 2017 Apr 5.
23 Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer.Mol Ther Nucleic Acids. 2019 Sep 6;17:256-263. doi: 10.1016/j.omtn.2019.06.002. Epub 2019 Jun 13.
24 Garcinol sensitizes human pancreatic adenocarcinoma cells to gemcitabine in association with microRNA signatures.Mol Nutr Food Res. 2013 Feb;57(2):235-48. doi: 10.1002/mnfr.201200297. Epub 2013 Jan 7.
25 Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection.Hum Immunol. 2010 Jun;71(6):621-6. doi: 10.1016/j.humimm.2010.02.017. Epub 2010 Mar 12.
26 Association of MicroRNA-196a2 Variant with Response to Short-Acting 2-Agonist in COPD: An Egyptian Pilot Study.PLoS One. 2016 Apr 4;11(4):e0152834. doi: 10.1371/journal.pone.0152834. eCollection 2016.
27 MicroRNA-125b may function as an oncogene in lung cancer cells.Mol Med Rep. 2015 May;11(5):3880-7. doi: 10.3892/mmr.2014.3142. Epub 2014 Dec 31.
28 The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs.Sci Transl Med. 2019 Jun 12;11(496):eaav1892. doi: 10.1126/scitranslmed.aav1892.
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32 Sh-MARCH8 Inhibits Tumorigenesis via PI3K Pathway in Gastric Cancer.Cell Physiol Biochem. 2018;49(1):306-321. doi: 10.1159/000492882. Epub 2018 Aug 23.
33 Mutation screening of MIR146A/B and BRCA1/2 3'-UTRs in the GENESIS study.Eur J Hum Genet. 2016 Aug;24(9):1324-9. doi: 10.1038/ejhg.2015.284. Epub 2016 Jan 20.
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36 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.
37 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
38 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.
39 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.
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