Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZN4FT3)

DOT Name Microfibrillar-associated protein 1 (MFAP1)
Synonyms Spliceosome B complex protein MFAP1
Gene Name MFAP1
Related Disease
Melanoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Choriocarcinoma ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Cystic fibrosis ( )
Danon disease ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Hyperglycemia ( )
Hyperlipidemia ( )
Hypertrophic cardiomyopathy ( )
Immunodeficiency ( )
Lung cancer ( )
Metabolic disorder ( )
Myocardial ischemia ( )
Neoplasm ( )
Neuroblastoma ( )
Neurofibromatosis type 1 ( )
Non-alcoholic fatty liver disease ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Osteosarcoma ( )
Parkinson disease ( )
Renal cell carcinoma ( )
Schizophrenia ( )
Wolff-Parkinson-White syndrome ( )
Adult glioblastoma ( )
Asthma ( )
Cardiovascular disease ( )
Glioblastoma multiforme ( )
Glioma ( )
Leukemia ( )
Type-1/2 diabetes ( )
Adult T-cell leukemia/lymphoma ( )
Carney complex ( )
Colon cancer ( )
Colon carcinoma ( )
Lung carcinoma ( )
UniProt ID
MFAP1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5F5S; 5O9Z; 6AHD; 7AAV; 7ABF; 7ABG; 7ABI
Pfam ID
PF06991
Sequence
MSVPSALMKQPPIQSTAGAVPVRNEKGEISMEKVKVKRYVSGKRPDYAPMESSDEEDEEF
QFIKKAKEQEAEPEEQEEDSSSDPRLRRLQNRISEDVEERLARHRKIVEPEVVGESDSEV
EGDAWRMEREDSSEEEEEEIDDEEIERRRGMMRQRAQERKNEEMEVMEVEDEGRSGEESE
SESEYEEYTDSEDEMEPRLKPVFIRKKDRVTVQEREAEALKQKELEQEAKRMAEERRKYT
LKIVEEETKKELEENKRSLAALDALNTDDENDEEEYEAWKVRELKRIKRDREDREALEKE
KAEIERMRNLTEEERRAELRANGKVITNKAVKGKYKFLQKYYHRGAFFMDEDEEVYKRDF
SAPTLEDHFNKTILPKVMQVKNFGRSGRTKYTHLVDQDTTSFDSAWGQESAQNTKFFKQK
AAGVRDVFERPSAKKRKTT
Function Involved in pre-mRNA splicing as a component of the spliceosome.
Reactome Pathway
mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Melanoma DIS1RRCY Definitive Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Arteriosclerosis DISK5QGC Strong Biomarker [4]
Atherosclerosis DISMN9J3 Strong Biomarker [4]
Bone osteosarcoma DIST1004 Strong Altered Expression [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Cardiac failure DISDC067 Strong Biomarker [7]
Choriocarcinoma DISDBVNL Strong Biomarker [8]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [10]
Congestive heart failure DIS32MEA Strong Biomarker [7]
Cystic fibrosis DIS2OK1Q Strong Biomarker [11]
Danon disease DIS45YLU Strong Genetic Variation [12]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [13]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [14]
High blood pressure DISY2OHH Strong Biomarker [15]
Hyperglycemia DIS0BZB5 Strong Genetic Variation [16]
Hyperlipidemia DIS61J3S Strong Genetic Variation [15]
Hypertrophic cardiomyopathy DISQG2AI Strong Genetic Variation [17]
Immunodeficiency DIS093I0 Strong Altered Expression [18]
Lung cancer DISCM4YA Strong Altered Expression [19]
Metabolic disorder DIS71G5H Strong Genetic Variation [20]
Myocardial ischemia DISFTVXF Strong Altered Expression [21]
Neoplasm DISZKGEW Strong Altered Expression [14]
Neuroblastoma DISVZBI4 Strong Biomarker [22]
Neurofibromatosis type 1 DIS53JH9 Strong Genetic Variation [23]
Non-alcoholic fatty liver disease DISDG1NL Strong Altered Expression [24]
Non-insulin dependent diabetes DISK1O5Z Strong Altered Expression [25]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [26]
Osteoarthritis DIS05URM Strong Altered Expression [27]
Osteosarcoma DISLQ7E2 Strong Altered Expression [5]
Parkinson disease DISQVHKL Strong Biomarker [28]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [9]
Schizophrenia DISSRV2N Strong Altered Expression [29]
Wolff-Parkinson-White syndrome DISW4TQ8 Strong Genetic Variation [30]
Adult glioblastoma DISVP4LU moderate Biomarker [31]
Asthma DISW9QNS moderate Biomarker [32]
Cardiovascular disease DIS2IQDX moderate Genetic Variation [33]
Glioblastoma multiforme DISK8246 moderate Biomarker [31]
Glioma DIS5RPEH moderate Altered Expression [34]
Leukemia DISNAKFL moderate Biomarker [35]
Type-1/2 diabetes DISIUHAP moderate Biomarker [36]
Adult T-cell leukemia/lymphoma DIS882XU Disputed Biomarker [37]
Carney complex DISVL3IP Disputed Genetic Variation [38]
Colon cancer DISVC52G Limited Biomarker [39]
Colon carcinoma DISJYKUO Limited Biomarker [39]
Lung carcinoma DISTR26C Limited Altered Expression [19]
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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 Microfibrillar-associated protein 1 (MFAP1). [40]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Microfibrillar-associated protein 1 (MFAP1). [41]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Microfibrillar-associated protein 1 (MFAP1). [42]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Microfibrillar-associated protein 1 (MFAP1). [43]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Microfibrillar-associated protein 1 (MFAP1). [45]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Microfibrillar-associated protein 1 (MFAP1). [48]
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⏷ Show the Full List of 6 Drug(s)
4 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 affects the methylation of Microfibrillar-associated protein 1 (MFAP1). [44]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Microfibrillar-associated protein 1 (MFAP1). [46]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Microfibrillar-associated protein 1 (MFAP1). [47]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of Microfibrillar-associated protein 1 (MFAP1). [49]
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References

1 Elevated cyclic AMP levels promote BRAF(CA)/Pten(-/-) mouse melanoma growth but pCREB is negatively correlated with human melanoma progression.Cancer Lett. 2018 Feb 1;414:268-277. doi: 10.1016/j.canlet.2017.11.027. Epub 2017 Nov 24.
2 MUL1 E3 ligase regulates the antitumor effects of metformin in chemoresistant ovarian cancer cells via AKT degradation.Int J Oncol. 2019 May;54(5):1833-1842. doi: 10.3892/ijo.2019.4730. Epub 2019 Feb 27.
3 Therapeutic Potential of AMP-Activated Protein Kinase in Alzheimer's Disease.J Alzheimers Dis. 2019;68(1):33-38. doi: 10.3233/JAD-181043.
4 A potential strategy for treating atherosclerosis: improving endothelial function via AMP-activated protein kinase.Sci China Life Sci. 2018 Sep;61(9):1024-1029. doi: 10.1007/s11427-017-9285-1. Epub 2018 Apr 16.
5 Capsaicin induces apoptosis in human osteosarcoma cells through AMPK-dependent and AMPK-independent signaling pathways.Mol Cell Biochem. 2013 Dec;384(1-2):229-37. doi: 10.1007/s11010-013-1802-8. Epub 2013 Sep 5.
6 Phytosomal-curcumin antagonizes cell growth and migration, induced by thrombin through AMP-Kinase in breast cancer.J Cell Biochem. 2018 Jul;119(7):5996-6007. doi: 10.1002/jcb.26796. Epub 2018 Mar 30.
7 Molecular Mechanism of the Association Between Atrial Fibrillation and Heart Failure Includes Energy Metabolic Dysregulation Due to Mitochondrial Dysfunction.J Card Fail. 2019 Nov;25(11):911-920. doi: 10.1016/j.cardfail.2019.08.005. Epub 2019 Aug 12.
8 RhoE is regulated by cyclic AMP and promotes fusion of human BeWo choriocarcinoma cells.PLoS One. 2012;7(1):e30453. doi: 10.1371/journal.pone.0030453. Epub 2012 Jan 17.
9 Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.Cell Physiol Biochem. 2018;45(3):1205-1218. doi: 10.1159/000487452. Epub 2018 Feb 9.
10 NPC-26 kills human colorectal cancer cells via activating AMPK signaling.Oncotarget. 2017 Mar 14;8(11):18312-18321. doi: 10.18632/oncotarget.15436.
11 Rattlesnake Phospholipase A2 Increases CFTR-Chloride Channel Current and Corrects F508CFTR Dysfunction: Impact in Cystic Fibrosis.J Mol Biol. 2016 Jul 17;428(14):2898-915. doi: 10.1016/j.jmb.2016.05.016. Epub 2016 May 27.
12 Activation of cardiac hypertrophic signaling pathways in a transgenic mouse with the human PRKAG2 Thr400Asn mutation.Biochim Biophys Acta. 2010 Feb;1802(2):284-91. doi: 10.1016/j.bbadis.2009.12.001. Epub 2009 Dec 11.
13 Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus.J Biol Chem. 2016 Jan 22;291(4):1974-1990. doi: 10.1074/jbc.M115.674861. Epub 2015 Dec 1.
14 Targeting AMP-activated kinase impacts hepatocellular cancer stem cells induced by long-term treatment with sorafenib.Mol Oncol. 2019 May;13(5):1311-1331. doi: 10.1002/1878-0261.12488. Epub 2019 Apr 15.
15 Nucleotide ecto-enzyme metabolic pattern and spatial distribution in calcific aortic valve disease; its relation to pathological changes and clinical presentation.Clin Res Cardiol. 2020 Feb;109(2):137-160. doi: 10.1007/s00392-019-01495-x. Epub 2019 May 29.
16 Blackcurrant Extract Ameliorates Hyperglycemia in Type 2 Diabetic Mice in Association with Increased Basal Secretion of Glucagon-Like Peptide-1 and Activation of AMP-Activated Protein Kinase.J Nutr Sci Vitaminol (Tokyo). 2018;64(4):258-264. doi: 10.3177/jnsv.64.258.
17 Cardiac transplant in a family pedigree of hypertrophic cardiomyopathy secondary to a mutation in the AMP gene.BMJ Case Rep. 2013 Aug 30;2013:bcr2013009929. doi: 10.1136/bcr-2013-009929.
18 An in vitro study of NF-B factors cooperatively in regulation of Drosophila melanogaster antimicrobial peptide genes.Dev Comp Immunol. 2019 Jun;95:50-58. doi: 10.1016/j.dci.2019.01.017. Epub 2019 Feb 6.
19 LCAL1 enhances lung cancer survival via inhibiting AMPK-related antitumor functions.Mol Cell Biochem. 2019 Jul;457(1-2):11-20. doi: 10.1007/s11010-019-03507-w. Epub 2019 Feb 11.
20 Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.EBioMedicine. 2018 May;31:122-132. doi: 10.1016/j.ebiom.2018.04.009. Epub 2018 Apr 8.
21 RNA sequencing revealing the role of AMP-activated protein kinase signaling in mice myocardial ischemia reperfusion injury.Gene. 2019 Jun 30;703:91-101. doi: 10.1016/j.gene.2019.04.010. Epub 2019 Apr 8.
22 Diminished iron concentrations increase adenosine A(2A) receptor levels in mouse striatum and cultured human neuroblastoma cells.Exp Neurol. 2009 Feb;215(2):236-42. doi: 10.1016/j.expneurol.2008.10.007. Epub 2008 Oct 28.
23 One NF1 Mutation may Conceal Another.Genes (Basel). 2019 Aug 22;10(9):633. doi: 10.3390/genes10090633.
24 Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling.Redox Biol. 2020 Jan;28:101315. doi: 10.1016/j.redox.2019.101315. Epub 2019 Sep 3.
25 BMP and mTOR signaling in heterotopic ossification: Does their crosstalk provide therapeutic opportunities?.J Cell Biochem. 2019 Aug;120(8):12108-12122. doi: 10.1002/jcb.28710. Epub 2019 Apr 15.
26 Decoction of Chinese Herbal Medicine Fuzheng Kang-Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl-2/Caspase-3 Pathway.Evid Based Complement Alternat Med. 2018 Jun 25;2018:8567905. doi: 10.1155/2018/8567905. eCollection 2018.
27 Homocysteine causes dysfunction of chondrocytes and oxidative stress through repression of SIRT1/AMPK pathway: A possible link between hyperhomocysteinemia and osteoarthritis.Redox Biol. 2018 May;15:504-512. doi: 10.1016/j.redox.2018.01.010. Epub 2018 Feb 3.
28 AMP Kinase Activation is Selectively Disrupted in the Ventral Midbrain of Mice Deficient in Parkin or PINK1 Expression.Neuromolecular Med. 2019 Mar;21(1):25-32. doi: 10.1007/s12017-018-8517-7. Epub 2018 Nov 8.
29 Modelling schizophrenia using human induced pluripotent stem cells.Nature. 2011 May 12;473(7346):221-5. doi: 10.1038/nature09915. Epub 2011 Apr 13.
30 Overexpression of G100S mutation in PRKAG2 causes Wolff-Parkinson-White syndrome in zebrafish.Clin Genet. 2014 Sep;86(3):287-91. doi: 10.1111/cge.12267. Epub 2013 Oct 25.
31 Author Correction: AMP kinase promotes glioblastoma bioenergetics and tumour growth.Nat Cell Biol. 2018 Nov;20(11):1328. doi: 10.1038/s41556-018-0203-3.
32 Contrasting effects of ATP and adenosine on capsaicin challenge in asthmatic patients.Pulm Pharmacol Ther. 2017 Aug;45:13-18. doi: 10.1016/j.pupt.2017.04.004. Epub 2017 Apr 6.
33 CardioVAI: An automatic implementation of ACMG-AMP variant interpretation guidelines in the diagnosis of cardiovascular diseases.Hum Mutat. 2018 Dec;39(12):1835-1846. doi: 10.1002/humu.23665. Epub 2018 Oct 19.
34 Activation of AMP-activated kinase modulates sensitivity of glioma cells against epidermal growth factor receptor inhibition.Int J Oncol. 2016 Jul;49(1):173-80. doi: 10.3892/ijo.2016.3498. Epub 2016 Apr 25.
35 Targeted Next-Generation Sequencing for Detecting MLL Gene Fusions in Leukemia.Mol Cancer Res. 2018 Feb;16(2):279-285. doi: 10.1158/1541-7786.MCR-17-0569. Epub 2017 Nov 13.
36 Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP.Front Pharmacol. 2019 Feb 19;10:98. doi: 10.3389/fphar.2019.00098. eCollection 2019.
37 VCAP-AMP-VECP as a preferable induction chemotherapy in transplant-eligible patients with aggressive adult T-cell leukemia-lymphoma: a propensity score analysis.Bone Marrow Transplant. 2019 Sep;54(9):1399-1405. doi: 10.1038/s41409-019-0446-z. Epub 2019 Jan 21.
38 Clinical phenotypes and molecular genetic mechanisms of Carney complex.Lancet Oncol. 2005 Jul;6(7):501-8. doi: 10.1016/S1470-2045(05)70244-8.
39 Adenine Inhibits the Growth of Colon Cancer Cells via AMP-Activated Protein Kinase Mediated Autophagy.Evid Based Complement Alternat Med. 2019 Sep 12;2019:9151070. doi: 10.1155/2019/9151070. eCollection 2019.
40 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.
41 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.
42 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.
43 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.
44 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.
45 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
46 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.
47 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
48 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
49 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.