Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTQ0J64)

DOT Name	Mitochondrial antiviral-signaling protein (MAVS)
Synonyms	MAVS; CARD adapter inducing interferon beta; Cardif; Interferon beta promoter stimulator protein 1; IPS-1; Putative NF-kappa-B-activating protein 031N; Virus-induced-signaling adapter; VISA
Gene Name	MAVS
Related Disease	Adenocarcinoma ( ) Bacteremia ( ) Bacterial endocarditis ( ) Castration-resistant prostate carcinoma ( ) Infective endocarditis ( ) Prostate neoplasm ( ) Advanced cancer ( ) Alphavirus infectious disease ( ) Chikungunya virus infection ( ) Cryohydrocytosis ( ) Dermatitis ( ) Disease of orbital part of eye adnexa ( ) Disorder of sexual differentiation ( ) Graft-versus-host disease ( ) Hepatitis A virus infection ( ) Immunodeficiency ( ) Influenza ( ) Leprosy ( ) Liver cirrhosis ( ) Lupus ( ) Methicillin-resistant staphylococci infection ( ) Multiple sclerosis ( ) Nervous system inflammation ( ) Polycythemia vera ( ) Psoriasis ( ) Zika virus infection ( ) Breast cancer ( ) Breast carcinoma ( ) Chronic obstructive pulmonary disease ( ) Osteoarthritis ( ) Tetralogy of fallot ( ) Toxic shock syndrome ( ) Autoimmune disease ( ) Bronchiolitis ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Chronic hepatitis B virus infection ( ) Dengue ( ) Ebola virus infection ( ) Enterovirus infection ( ) Hepatocellular carcinoma ( ) Liver cancer ( ) Melanoma ( ) Neoplasm ( )
UniProt ID	MAVS_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2MS7; 2MS8; 2VGQ; 3J6C; 3J6J; 3RC5; 4P4H; 4Z8M; 5JEK; 7DNI
Pfam ID	PF16739
Sequence	MPFAEDKTYKYICRNFSNFCNVDVVEILPYLPCLTARDQDRLRATCTLSGNRDTLWHLFN TLQRRPGWVEYFIAALRGCELVDLADEVASVYQSYQPRTSDRPPDPLEPPSLPAERPGPP TPAAAHSIPYNSCREKEPSYPMPVQETQAPESPGENSEQALQTLSPRAIPRNPDGGPLES SSDLAALSPLTSSGHQEQDTELGSTHTAGATSSLTPSRGPVSPSVSFQPLARSTPRASRL PGPTGSVVSTGTSFSSSSPGLASAGAAEGKQGAESDQAEPIICSSGAEAPANSLPSKVPT TLMPVNTVALKVPANPASVSTVPSKLPTSSKPPGAVPSNALTNPAPSKLPINSTRAGMVP SKVPTSMVLTKVSASTVPTDGSSRNEETPAAPTPAGATGGSSAWLDSSSENRGLGSELSK PGVLASQVDSPFSGCFEDLAISASTSLGMGPCHGPEENEYKSEGTFGIHVAENPSIQLLE GNPGPPADPDGGPRPQADRKFQEREVPCHRPSPGALWLQVAVTGVLVVTLLVVLYRRRLH
Function	Adapter required for innate immune defense against viruses. Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFNB and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis. Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria.
Tissue Specificity	Present in T-cells, monocytes, epithelial cells and hepatocytes (at protein level). Ubiquitously expressed, with highest levels in heart, skeletal muscle, liver, placenta and peripheral blood leukocytes.
KEGG Pathway	NOD-like receptor sig.ling pathway (hsa04621 ) RIG-I-like receptor sig.ling pathway (hsa04622 ) Cytosolic D.-sensing pathway (hsa04623 ) Hepatitis C (hsa05160 ) Hepatitis B (hsa05161 ) Measles (hsa05162 ) Influenza A (hsa05164 ) Herpes simplex virus 1 infection (hsa05168 ) Epstein-Barr virus infection (hsa05169 ) Coro.virus disease - COVID-19 (hsa05171 )
Reactome Pathway	Ovarian tumor domain proteases (R-HSA-5689896 ) TRAF3-dependent IRF activation pathway (R-HSA-918233 ) TRAF6 mediated IRF7 activation (R-HSA-933541 ) TRAF6 mediated NF-kB activation (R-HSA-933542 ) NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 (R-HSA-933543 ) Negative regulators of DDX58/IFIH1 signaling (R-HSA-936440 ) SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916 ) SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671 ) PKR-mediated signaling (R-HSA-9833482 ) DDX58/IFIH1-mediated induction of interferon-alpha/beta (R-HSA-168928 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[1]
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[2]
Bacterial endocarditis	DIS920N0	Definitive	Biomarker	[2]
Castration-resistant prostate carcinoma	DISVGAE6	Definitive	Biomarker	[1]
Infective endocarditis	DIS88NSA	Definitive	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alphavirus infectious disease	DISZGSCJ	Strong	Biomarker	[4]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[4]
Cryohydrocytosis	DISMQHL3	Strong	Altered Expression	[5]
Dermatitis	DISY5SZC	Strong	Biomarker	[6]
Disease of orbital part of eye adnexa	DISGWPWX	Strong	Biomarker	[7]
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[8]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[9]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[10]
Immunodeficiency	DIS093I0	Strong	Biomarker	[11]
Influenza	DIS3PNU3	Strong	Biomarker	[12]
Leprosy	DISAA4UI	Strong	Genetic Variation	[13]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[14]
Lupus	DISOKJWA	Strong	Biomarker	[15]
Methicillin-resistant staphylococci infection	DIS6DRDZ	Strong	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[17]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[18]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[19]
Psoriasis	DIS59VMN	Strong	Biomarker	[20]
Zika virus infection	DISQUCTY	Strong	Biomarker	[21]
Breast cancer	DIS7DPX1	moderate	Biomarker	[22]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[22]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[23]
Osteoarthritis	DIS05URM	moderate	Biomarker	[24]
Tetralogy of fallot	DISMHFNW	moderate	Biomarker	[25]
Toxic shock syndrome	DISX5S53	Disputed	Biomarker	[26]
Autoimmune disease	DISORMTM	Limited	Altered Expression	[27]
Bronchiolitis	DISEE9BG	Limited	Biomarker	[28]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[29]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Altered Expression	[14]
Dengue	DISKH221	Limited	Altered Expression	[30]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[31]
Enterovirus infection	DISH2UDP	Limited	Biomarker	[32]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[14]
Liver cancer	DISDE4BI	Limited	Biomarker	[29]
Melanoma	DIS1RRCY	Limited	Altered Expression	[33]
Neoplasm	DISZKGEW	Limited	Altered Expression	[34]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 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 Mitochondrial antiviral-signaling protein (MAVS).	[35]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial antiviral-signaling protein (MAVS).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Mitochondrial antiviral-signaling protein (MAVS).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Mitochondrial antiviral-signaling protein (MAVS).	[45]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[43]
Marinol	DM70IK5	Approved	Marinol increases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[44]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the expression of Mitochondrial antiviral-signaling protein (MAVS).	[43]
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⏷ Show the Full List of 9 Drug(s)

References

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24	Identification of MAVS as a Novel Risk Factor for the Development of Osteoarthritis.Aging Dis. 2018 Feb 1;9(1):40-50. doi: 10.14336/AD.2017.0308. eCollection 2018 Feb.
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27	DNAJB1/HSP40 Suppresses Melanoma Differentiation-Associated Gene 5-Mitochondrial Antiviral Signaling Protein Function in Conjunction with HSP70.J Innate Immun. 2018;10(1):44-55. doi: 10.1159/000480740. Epub 2017 Oct 26.
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32	Correction: Enterovirus 71 Protease 2Apro Targets MAVS to Inhibit Anti-Viral Type I Interferon Responses.PLoS Pathog. 2017 Mar 2;13(3):e1006243. doi: 10.1371/journal.ppat.1006243. eCollection 2017 Mar.
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