Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTF68DC)

DOT Name Alpha-adducin (ADD1)
Synonyms Erythrocyte adducin subunit alpha
Gene Name ADD1
Related Disease
Chronic kidney disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Cardiac failure ( )
Classic Hodgkin lymphoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Coronary atherosclerosis ( )
Dehydrated hereditary stomatocytosis ( )
Gastric cancer ( )
Huntington disease ( )
Hydrocephalus ( )
Hyperaldosteronism ( )
Hyperlipidemia, familial combined, LPL related ( )
IgA nephropathy ( )
Kidney failure ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Nephropathy ( )
Non-small-cell lung cancer ( )
Peripheral arterial disease ( )
Primary aldosteronism ( )
Stomach cancer ( )
Stroke ( )
Temporal lobe epilepsy ( )
Cardiovascular disease ( )
Diabetic kidney disease ( )
Endolymphatic hydrops ( )
Hypertension, pregnancy-induced ( )
Meniere disease ( )
Acute myelogenous leukaemia ( )
Coronary heart disease ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Leukemia ( )
Meningococcal disease ( )
Non-insulin dependent diabetes ( )
T-cell acute lymphoblastic leukaemia ( )
Type-1/2 diabetes ( )
UniProt ID
ADDA_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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Pfam ID
PF00596
Sequence
MNGDSRAAVVTSPPPTTAPHKERYFDRVDENNPEYLRERNMAPDLRQDFNMMEQKKRVSM
ILQSPAFCEELESMIQEQFKKGKNPTGLLALQQIADFMTTNVPNVYPAAPQGGMAALNMS
LGMVTPVNDLRGSDSIAYDKGEKLLRCKLAAFYRLADLFGWSQLIYNHITTRVNSEQEHF
LIVPFGLLYSEVTASSLVKINLQGDIVDRGSTNLGVNQAGFTLHSAIYAARPDVKCVVHI
HTPAGAAVSAMKCGLLPISPEALSLGEVAYHDYHGILVDEEEKVLIQKNLGPKSKVLILR
NHGLVSVGESVEEAFYYIHNLVVACEIQVRTLASAGGPDNLVLLNPEKYKAKSRSPGSPV
GEGTGSPPKWQIGEQEFEALMRMLDNLGYRTGYPYRYPALREKSKKYSDVEVPASVTGYS
FASDGDSGTCSPLRHSFQKQQREKTRWLNSGRGDEASEEGQNGSSPKSKTKWTKEDGHRT
STSAVPNLFVPLNTNPKEVQEMRNKIREQNLQDIKTAGPQSQVLCGVVMDRSLVQGELVT
ASKAIIEKEYQPHVIVSTTGPNPFTTLTDRELEEYRREVERKQKGSEENLDEAREQKEKS
PPDQPAVPHPPPSTPIKLEEDLVPEPTTGDDSDAATFKPTLPDLSPDEPSEALGFPMLEK
EEEAHRPPSPTEAPTEASPEPAPDPAPVAEEAAPSAVEEGAAADPGSDGSPGKSPSKKKK
KFRTPSFLKKSKKKSDS
Function Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.
Tissue Specificity Expressed in all tissues. Found in much higher levels in reticulocytes than the beta subunit.
Reactome Pathway
XBP1(S) activates chaperone genes (R-HSA-381038 )
Miscellaneous transport and binding events (R-HSA-5223345 )
Caspase-mediated cleavage of cytoskeletal proteins (R-HSA-264870 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic kidney disease DISW82R7 Definitive Biomarker [1]
Arteriosclerosis DISK5QGC Strong Genetic Variation [2]
Atherosclerosis DISMN9J3 Strong Genetic Variation [2]
Cardiac failure DISDC067 Strong Genetic Variation [3]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [5]
Congestive heart failure DIS32MEA Strong Genetic Variation [3]
Coronary atherosclerosis DISKNDYU Strong Genetic Variation [6]
Dehydrated hereditary stomatocytosis DISGQT6H Strong Genetic Variation [7]
Gastric cancer DISXGOUK Strong Genetic Variation [5]
Huntington disease DISQPLA4 Strong Genetic Variation [8]
Hydrocephalus DISIZUF7 Strong Biomarker [9]
Hyperaldosteronism DIS3WGAL Strong Genetic Variation [10]
Hyperlipidemia, familial combined, LPL related DISL1CE3 Strong Genetic Variation [11]
IgA nephropathy DISZ8MTK Strong Genetic Variation [12]
Kidney failure DISOVQ9P Strong Genetic Variation [13]
Lung cancer DISCM4YA Strong Biomarker [14]
Lung carcinoma DISTR26C Strong Biomarker [14]
Neoplasm DISZKGEW Strong Biomarker [15]
Nephropathy DISXWP4P Strong Genetic Variation [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [17]
Peripheral arterial disease DIS78WFB Strong Genetic Variation [18]
Primary aldosteronism DISOEFNH Strong Biomarker [10]
Stomach cancer DISKIJSX Strong Genetic Variation [5]
Stroke DISX6UHX Strong Genetic Variation [19]
Temporal lobe epilepsy DISNOPXX Strong Biomarker [20]
Cardiovascular disease DIS2IQDX moderate Genetic Variation [21]
Diabetic kidney disease DISJMWEY moderate Genetic Variation [16]
Endolymphatic hydrops DISUPJBC moderate Genetic Variation [22]
Hypertension, pregnancy-induced DISHNU25 moderate Genetic Variation [23]
Meniere disease DISC5R5F moderate Genetic Variation [22]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [24]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [25]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [26]
leukaemia DISS7D1V Limited Biomarker [24]
Leukemia DISNAKFL Limited Biomarker [24]
Meningococcal disease DISGDM2Z Limited Genetic Variation [27]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [28]
T-cell acute lymphoblastic leukaemia DIS17AI2 Limited Genetic Variation [24]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [29]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Alpha-adducin (ADD1). [30]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Alpha-adducin (ADD1). [31]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Alpha-adducin (ADD1). [32]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Alpha-adducin (ADD1). [33]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Alpha-adducin (ADD1). [34]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Alpha-adducin (ADD1). [35]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Alpha-adducin (ADD1). [37]
Selenium DM25CGV Approved Selenium increases the expression of Alpha-adducin (ADD1). [38]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Alpha-adducin (ADD1). [38]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Alpha-adducin (ADD1). [40]
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⏷ Show the Full List of 10 Drug(s)
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin increases the phosphorylation of Alpha-adducin (ADD1). [36]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Alpha-adducin (ADD1). [39]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Alpha-adducin (ADD1). [36]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Alpha-adducin (ADD1). [36]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of Alpha-adducin (ADD1). [41]
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References

1 Genetic polymorphisms and the risk of accelerated renal function decline in women.PLoS One. 2009;4(3):e4787. doi: 10.1371/journal.pone.0004787. Epub 2009 Mar 10.
2 ACE and ADD1 gene in extra and intracranial atherosclerosis in ischaemic stroke.Neurol Res. 2013 May;35(4):429-34. doi: 10.1179/1743132813Y.0000000161.
3 Angiotensin-converting enzyme I/D and alpha-adducin Gly460Trp polymorphisms: from angiotensin-converting enzyme activity to cardiovascular outcome.Hypertension. 2007 Jun;49(6):1291-7. doi: 10.1161/HYPERTENSIONAHA.106.085498. Epub 2007 Apr 23.
4 Characterization of add(1)(p36) in non-Hodgkin lymphomas by fluorescence in situ hybridization.Genes Chromosomes Cancer. 1995 May;13(1):34-9. doi: 10.1002/gcc.2870130106.
5 A phosphorylation-related variant ADD1-rs4963 modifies the risk of colorectal cancer.PLoS One. 2015 Mar 27;10(3):e0121485. doi: 10.1371/journal.pone.0121485. eCollection 2015.
6 Association of alpha-adducin Gly460Trp polymorphism with coronary artery disease in a Korean population.J Hypertens. 2007 Dec;25(12):2413-20. doi: 10.1097/HJH.0b013e3282efedb5.
7 Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis.Am J Hematol. 1999 Jan;60(1):72-4. doi: 10.1002/(sici)1096-8652(199901)60:1<72::aid-ajh13>3.0.co;2-8.
8 Common SNP-based haplotype analysis of the 4p16.3 Huntington disease gene region.Am J Hum Genet. 2012 Mar 9;90(3):434-44. doi: 10.1016/j.ajhg.2012.01.005. Epub 2012 Mar 1.
9 Targeted deletion of alpha-adducin results in absent beta- and gamma-adducin, compensated hemolytic anemia, and lethal hydrocephalus in mice.Blood. 2008 Nov 15;112(10):4298-307. doi: 10.1182/blood-2008-05-156000. Epub 2008 Aug 22.
10 Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.J Clin Endocrinol Metab. 2002 Jul;87(7):3337-43. doi: 10.1210/jcem.87.7.8666.
11 Association between the alpha-adducin Gly460Trp polymorphism and systolic blood pressure in familial combined hyperlipidemia.Am J Hypertens. 2001 Dec;14(12):1185-90. doi: 10.1016/s0895-7061(01)02216-6.
12 The effects of both single-locus and multi-locus interaction on the clinical manifestations of IgA nephropathy in Southern Han Chinese.Nephrol Dial Transplant. 2014 Mar;29(3):550-5. doi: 10.1093/ndt/gft468. Epub 2013 Nov 21.
13 Alpha-adducin and angiotensin-converting enzyme polymorphisms in hypertension: evidence for a joint influence on albuminuria.J Hypertens. 2006 May;24(5):931-7. doi: 10.1097/01.hjh.0000222764.92229.6d.
14 AKT-mediated phosphorylation enhances protein stability and transcription activity of ZNF322A to promote lung cancer progression.Oncogene. 2019 Oct;38(41):6723-6736. doi: 10.1038/s41388-019-0928-x. Epub 2019 Aug 9.
15 Multifunctional Peptide-Amphiphile End-Capped Mesoporous Silica Nanoparticles for Tumor Targeting Drug Delivery.ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2093-2103. doi: 10.1021/acsami.6b12647. Epub 2017 Jan 12.
16 Role of alpha-adducin DNA polymorphisms in the genetic predisposition to diabetic nephropathy.Nephrol Dial Transplant. 2004 Aug;19(8):2019-24. doi: 10.1093/ndt/gfh342. Epub 2004 Jun 8.
17 Adducins inhibit lung cancer cell migration through mechanisms involving regulation of cell-matrix adhesion and cadherin-11 expression.Biochim Biophys Acta Mol Cell Res. 2019 Mar;1866(3):395-408. doi: 10.1016/j.bbamcr.2018.10.001. Epub 2018 Oct 2.
18 ADD1 460W allele associated with cardiovascular disease in hypertensive individuals.Hypertension. 2002 Jun;39(6):1053-7. doi: 10.1161/01.hyp.0000019128.94483.3a.
19 A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke.Clin Chim Acta. 2011 Mar 18;412(7-8):642-6. doi: 10.1016/j.cca.2010.12.022. Epub 2010 Dec 29.
20 Kainate-induced seizures alter protein composition and N-methyl-D-aspartate receptor function of rat forebrain postsynaptic densities.Neuroscience. 2001;102(1):65-74. doi: 10.1016/s0306-4522(00)00469-3.
21 Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study.Pharmacogenomics J. 2007 Apr;7(2):112-22. doi: 10.1038/sj.tpj.6500395. Epub 2006 May 16.
22 Gly460Trp alpha-adducin mutation as a possible mechanism leading to endolymphatic hydrops in Mnire's syndrome.Otol Neurotol. 2008 Sep;29(6):824-8. doi: 10.1097/MAO.0b013e318180a4b1.
23 Angiotensin-converting enzyme and adducin-1 polymorphisms in women with preeclampsia and gestational hypertension.Reprod Sci. 2009 Sep;16(9):819-26. doi: 10.1177/1933719109336612. Epub 2009 May 14.
24 T-cell acute lymphoblastic leukemia with add(1)(p36) and del(12)(p11) following acute myelocytic leukemia with partial deletion of 9p.Cancer Genet Cytogenet. 2004 Apr 1;150(1):62-5. doi: 10.1016/j.cancergencyto.2003.08.003.
25 Alpha-adducin polymorphism associated with increased risk of adverse cardiovascular outcomes: results from GENEtic Substudy of the INternational VErapamil SR-trandolapril STudy (INVEST-GENES).Am Heart J. 2008 Aug;156(2):397-404. doi: 10.1016/j.ahj.2008.03.007. Epub 2008 Jun 20.
26 Discrimination of tumorigenic triazole conazoles from phenobarbital by transcriptional analyses of mouse liver gene expression.Toxicol Sci. 2009 Jul;110(1):68-83. doi: 10.1093/toxsci/kfp076. Epub 2009 Apr 10.
27 Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection.Pediatr Crit Care Med. 2008 Sep;9(5):517-23. doi: 10.1097/PCC.0b013e318184985b.
28 The alpha-adducin gene is associated with macrovascular complications and mortality in patients with type 2 diabetes.Diabetes. 2006 Oct;55(10):2922-7. doi: 10.2337/db06-0302.
29 Synergistic Association of Genetic Variants with Environmental Risk Factors in Susceptibility to Essential Hypertension.Genet Test Mol Biomarkers. 2017 Oct;21(10):625-631. doi: 10.1089/gtmb.2017.0048. Epub 2017 Sep 5.
30 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.
31 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.
32 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.
33 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
34 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
35 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.
36 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.
37 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
38 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
39 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.
40 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
41 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.