Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYM8A2N)

DOT Name Adenylyl cyclase-associated protein 1 (CAP1)
Synonyms CAP 1
Gene Name CAP1
Related Disease
Non-insulin dependent diabetes ( )
Tuberculosis ( )
Arrhythmia ( )
Bacteremia ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Chronic obstructive pulmonary disease ( )
Colitis ( )
Colorectal carcinoma ( )
Epilepsy ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Fatty liver disease ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Influenza ( )
Non-alcoholic fatty liver disease ( )
Osteoporosis ( )
Perry syndrome ( )
Pneumonia ( )
Prostate neoplasm ( )
Squamous cell carcinoma ( )
Thalassemia ( )
Type-1/2 diabetes ( )
Adult glioblastoma ( )
Carcinoma ( )
Glioblastoma multiforme ( )
Invasive breast carcinoma ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Adenocarcinoma ( )
Arteriosclerosis ( )
Asthma ( )
Atherosclerosis ( )
Bone osteosarcoma ( )
Chronic kidney disease ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Gastric cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Stomach cancer ( )
Stroke ( )
UniProt ID
CAP1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1K8F
Pfam ID
PF08603 ; PF01213
Sequence
MADMQNLVERLERAVGRLEAVSHTSDMHRGYADSPSKAGAAPYVQAFDSLLAGPVAEYLK
ISKEIGGDVQKHAEMVHTGLKLERALLVTASQCQQPAENKLSDLLAPISEQIKEVITFRE
KNRGSKLFNHLSAVSESIQALGWVAMAPKPGPYVKEMNDAAMFYTNRVLKEYKDVDKKHV
DWVKAYLSIWTELQAYIKEFHTTGLAWSKTGPVAKELSGLPSGPSAGSCPPPPPPCPPPP
PVSTISCSYESASRSSLFAQINQGESITHALKHVSDDMKTHKNPALKAQSGPVRSGPKPF
SAPKPQTSPSPKRATKKEPAVLELEGKKWRVENQENVSNLVIEDTELKQVAYIYKCVNTT
LQIKGKINSITVDNCKKLGLVFDDVVGIVEIINSKDVKVQVMGKVPTISINKTDGCHAYL
SKNSLDCEIVSAKSSEMNVLIPTEGGDFNEFPVPEQFKTLWNGQKLVTTVTEIAG
Function Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity.
Reactome Pathway
Role of ABL in ROBO-SLIT signaling (R-HSA-428890 )
Neutrophil degranulation (R-HSA-6798695 )
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Non-insulin dependent diabetes DISK1O5Z Definitive Biomarker [1]
Tuberculosis DIS2YIMD Definitive Biomarker [2]
Arrhythmia DISFF2NI Strong Genetic Variation [3]
Bacteremia DIS6N9RZ Strong Genetic Variation [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Chronic obstructive pulmonary disease DISQCIRF Strong Biomarker [8]
Colitis DISAF7DD Strong Genetic Variation [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Epilepsy DISBB28L Strong Biomarker [11]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [12]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [13]
Fatty liver disease DIS485QZ Strong Biomarker [14]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
Influenza DIS3PNU3 Strong Biomarker [17]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [18]
Osteoporosis DISF2JE0 Strong Biomarker [19]
Perry syndrome DIS8YKKM Strong Genetic Variation [20]
Pneumonia DIS8EF3M Strong Biomarker [21]
Prostate neoplasm DISHDKGQ Strong Genetic Variation [22]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [23]
Thalassemia DIS76XZB Strong Genetic Variation [24]
Type-1/2 diabetes DISIUHAP Strong Biomarker [25]
Adult glioblastoma DISVP4LU moderate Biomarker [26]
Carcinoma DISH9F1N moderate Biomarker [27]
Glioblastoma multiforme DISK8246 moderate Biomarker [26]
Invasive breast carcinoma DISANYTW moderate Biomarker [28]
Pancreatic cancer DISJC981 moderate Biomarker [29]
Prostate cancer DISF190Y moderate Biomarker [30]
Prostate carcinoma DISMJPLE moderate Biomarker [30]
Adenocarcinoma DIS3IHTY Limited Biomarker [31]
Arteriosclerosis DISK5QGC Limited Biomarker [32]
Asthma DISW9QNS Limited Biomarker [33]
Atherosclerosis DISMN9J3 Limited Biomarker [32]
Bone osteosarcoma DIST1004 Limited Biomarker [34]
Chronic kidney disease DISW82R7 Limited Biomarker [32]
Coronary atherosclerosis DISKNDYU Limited Biomarker [35]
Coronary heart disease DIS5OIP1 Limited Biomarker [35]
Gastric cancer DISXGOUK Limited Genetic Variation [36]
Lung cancer DISCM4YA Limited Altered Expression [31]
Lung carcinoma DISTR26C Limited Altered Expression [31]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [37]
Osteosarcoma DISLQ7E2 Limited Biomarker [34]
Stomach cancer DISKIJSX Limited Genetic Variation [36]
Stroke DISX6UHX Limited Biomarker [38]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
4-hydroxy-2-nonenal DM2LJFZ Investigative Adenylyl cyclase-associated protein 1 (CAP1) affects the binding of 4-hydroxy-2-nonenal. [53]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [39]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [40]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [41]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [42]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Adenylyl cyclase-associated protein 1 (CAP1). [43]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [44]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [45]
Ivermectin DMDBX5F Approved Ivermectin affects the expression of Adenylyl cyclase-associated protein 1 (CAP1). [46]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [47]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [48]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [51]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of Adenylyl cyclase-associated protein 1 (CAP1). [52]
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⏷ Show the Full List of 12 Drug(s)
2 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 decreases the methylation of Adenylyl cyclase-associated protein 1 (CAP1). [49]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Adenylyl cyclase-associated protein 1 (CAP1). [50]
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References

1 Capsaicin reduces Alzheimer-associated tau changes in the hippocampus of type 2 diabetes rats.PLoS One. 2017 Feb 22;12(2):e0172477. doi: 10.1371/journal.pone.0172477. eCollection 2017.
2 Diagnostic accuracy study of multiplex PCR for detecting tuberculosis drug resistance.J Infect. 2015 Aug;71(2):220-30. doi: 10.1016/j.jinf.2015.03.011. Epub 2015 Apr 30.
3 Quality of life benefits from arrhythmia ablation: A longitudinal study using the C-CAP questionnaire and EQ5D.Pacing Clin Electrophysiol. 2019 Jun;42(6):705-711. doi: 10.1111/pace.13675. Epub 2019 Apr 17.
4 The efficacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta-analysis.Ann Clin Microbiol Antimicrob. 2017 Apr 5;16(1):24. doi: 10.1186/s12941-017-0199-8.
5 Assessment of ERBB2/HER2 Status in HER2-Equivocal Breast Cancers by FISH and 2013/2014 ASCO-CAP Guidelines.JAMA Oncol. 2019 Mar 1;5(3):366-375. doi: 10.1001/jamaoncol.2018.6012.
6 What to expect from the 2018 ASCO/CAP HER2 guideline in the reflex in situ hybridization test of immunohistochemically equivocal 2+ cases?.Virchows Arch. 2019 Sep;475(3):303-311. doi: 10.1007/s00428-019-02567-z. Epub 2019 Apr 5.
7 Antineoplastic effect of pectic polysaccharides from green sweet pepper (Capsicum annuum) on mammary tumor cells in vivo and in vitro.Carbohydr Polym. 2018 Dec 1;201:280-292. doi: 10.1016/j.carbpol.2018.08.071. Epub 2018 Aug 20.
8 Relationship between expression of matrix metalloproteinase-9 and adenylyl cyclase-associated protein 1 in chronic obstructive pulmonary disease.J Int Med Res. 2014 Dec;42(6):1272-84. doi: 10.1177/0300060514548290. Epub 2014 Oct 20.
9 In situ self-spray coating system that can uniformly disperse a poorly water-soluble H(2)S donor on the colorectal surface to treat inflammatory bowel diseases.Biomaterials. 2018 Nov;182:289-298. doi: 10.1016/j.biomaterials.2018.07.044. Epub 2018 Aug 16.
10 Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine.EPMA J. 2019 Jul 20;10(3):307-316. doi: 10.1007/s13167-019-00178-x. eCollection 2019 Sep.
11 Earlyonset epilepsy and microcephalycapillary malformation syndrome caused by a novel STAMBP mutation in a Chinese boy.Mol Med Rep. 2019 Dec;20(6):5145-5151. doi: 10.3892/mmr.2019.10757. Epub 2019 Oct 17.
12 CAP1 is overexpressed in human epithelial ovarian cancer and promotes cell proliferation.Int J Mol Med. 2015 Apr;35(4):941-9. doi: 10.3892/ijmm.2015.2089. Epub 2015 Feb 4.
13 Downregulated expression of the cyclase-associated protein 1 (CAP1) reduces migration in esophageal squamous cell carcinoma.Jpn J Clin Oncol. 2013 Sep;43(9):856-64. doi: 10.1093/jjco/hyt093. Epub 2013 Jul 30.
14 Effect of Non-alcoholic Fatty Liver Disease on Transaminase Levels and Transient Elastography in Patients with Chronic Hepatitis B.Cureus. 2019 Oct 25;11(10):e5995. doi: 10.7759/cureus.5995.
15 Development of a new duplex real-time polymerase chain reaction assay for hepatitis B viral DNA detection.Virol J. 2011 May 14;8:227. doi: 10.1186/1743-422X-8-227.
16 Role of exosomes in hepatocellular carcinoma cell mobility alteration.Oncol Lett. 2017 Dec;14(6):8122-8131. doi: 10.3892/ol.2017.7257. Epub 2017 Oct 23.
17 DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response.Virol J. 2019 Feb 20;16(1):21. doi: 10.1186/s12985-019-1125-9.
18 Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis.Hepatology. 2018 Apr;67(4):1348-1359. doi: 10.1002/hep.29639. Epub 2018 Feb 19.
19 Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density.Proteomics. 2008 Oct;8(20):4259-72. doi: 10.1002/pmic.200700480.
20 Disease-associated mutations in the p150(Glued) subunit destabilize the CAP-gly domain.Biochemistry. 2010 Jun 29;49(25):5083-5. doi: 10.1021/bi100235z.
21 A case-control study of community-acquired Acinetobacter baumannii pneumonia and melioidosis pneumonia in northeast Thailand: an emerging fatal disease with unique clinical features.Diagn Microbiol Infect Dis. 2017 Jan;87(1):79-86. doi: 10.1016/j.diagmicrobio.2016.10.014. Epub 2016 Oct 11.
22 Comparative RNA-seq analysis reveals dys-regulation of major canonical pathways in ERG-inducible LNCaP cell progression model of prostate cancer.Oncotarget. 2019 Jul 2;10(42):4290-4306. doi: 10.18632/oncotarget.27019. eCollection 2019 Jul 2.
23 Different expression patterns of calpain isozymes 1 and 2 (CAPN1 and 2) in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of human skin.J Pathol. 2003 Apr;199(4):509-16. doi: 10.1002/path.1308.
24 Borderline hemoglobin A(2) levels in northern Thai population: HBB genotypes and effects of coinherited alpha-thalassemia.Blood Cells Mol Dis. 2019 Feb;74:13-17. doi: 10.1016/j.bcmd.2018.10.002. Epub 2018 Oct 4.
25 Liver fibrosis by FibroScan() independently of established cardiovascular risk parameters associates with macrovascular and microvascular complications in patients with type 2 diabetes.Liver Int. 2020 Feb;40(2):347-354. doi: 10.1111/liv.14274. Epub 2019 Oct 31.
26 A Novel Micro Cold Atmospheric Plasma Device for Glioblastoma Both In Vitro and In Vivo.Cancers (Basel). 2017 May 30;9(6):61. doi: 10.3390/cancers9060061.
27 Cyclase-associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells.Cell Biochem Funct. 2019 Apr;37(3):185-192. doi: 10.1002/cbf.3387. Epub 2019 Mar 8.
28 Assessment of dual-probe Her-2 fluorescent in situ hybridization in breast cancer by the 2013 ASCO/CAP guidelines produces more equivocal results than that by the 2007 ASCO/CAP guidelines.Breast Cancer Res Treat. 2016 Aug;159(1):31-9. doi: 10.1007/s10549-016-3917-6. Epub 2016 Jul 25.
29 Phosphorylation Regulates CAP1 (Cyclase-Associated Protein 1) Functions in the Motility and Invasion of Pancreatic Cancer Cells.Sci Rep. 2019 Mar 20;9(1):4925. doi: 10.1038/s41598-019-41346-3.
30 Urinary biomarkers in prostate cancer detection and monitoring progression.Crit Rev Oncol Hematol. 2017 Oct;118:15-26. doi: 10.1016/j.critrevonc.2017.08.002. Epub 2017 Aug 19.
31 Overexpression of adenylate cyclase-associated protein 1 is associated with metastasis of lung cancer.Oncol Rep. 2013 Oct;30(4):1639-44. doi: 10.3892/or.2013.2607. Epub 2013 Jul 9.
32 Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls.Cardiorenal Med. 2020;10(1):51-60. doi: 10.1159/000503416. Epub 2019 Nov 13.
33 Pseudotyped adeno-associated virus 2/9-delivered CCL11 shRNA alleviates lung inflammation in an allergen-sensitized mouse model.Hum Gene Ther. 2012 Nov;23(11):1156-65. doi: 10.1089/hum.2012.012. Epub 2012 Oct 19.
34 Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells.J Exp Clin Cancer Res. 2018 Oct 4;37(1):244. doi: 10.1186/s13046-018-0914-0.
35 Association of adenylate cyclase-associated protein 1 with coronary artery disease.Eur J Clin Invest. 2017 Sep;47(9):659-666. doi: 10.1111/eci.12787. Epub 2017 Aug 4.
36 A novel scoring system for gastric cancer risk assessment based on the expression of three CLIP4 DNA methylation-associated genes.Int J Oncol. 2018 Aug;53(2):633-643. doi: 10.3892/ijo.2018.4433. Epub 2018 Jun 6.
37 Adenylyl cyclaseassociated protein1targeted nanoparticles as a novel strategy for the treatment of metastatic nonsmall cell lung cancer.Int J Oncol. 2019 Aug;55(2):462-472. doi: 10.3892/ijo.2019.4822. Epub 2019 Jun 6.
38 Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries.J Am Coll Cardiol. 2019 Dec 10;74(23):2878-2889. doi: 10.1016/j.jacc.2019.09.064.
39 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
40 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
41 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.
42 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.
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44 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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46 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.
47 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.
48 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.
49 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.
50 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.
51 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.
52 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
53 Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: protein carbonylation is diminished by ascorbic acid. Chem Res Toxicol. 2010 Jan;23(1):37-47. doi: 10.1021/tx9002462.