Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFO915U)

DOT Name	Caveolae-associated protein 1 (CAVIN1)
Synonyms	Cavin-1; Polymerase I and transcript release factor
Gene Name	CAVIN1
Related Disease	Adult glioblastoma ( ) Advanced cancer ( ) Arrhythmia ( ) Colorectal carcinoma ( ) Congenital generalized lipodystrophy ( ) Congenital generalized lipodystrophy type 4 ( ) Ewing sarcoma ( ) Familial partial lipodystrophy ( ) Fatty liver disease ( ) Generalized lipodystrophy ( ) Glioma ( ) Hepatitis C virus infection ( ) Hyperinsulinemia ( ) Hypertrophic cardiomyopathy ( ) Liposarcoma ( ) Liver cirrhosis ( ) Long QT syndrome ( ) Myopathy ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Obesity ( ) Prostate cancer ( ) Prostate carcinoma ( ) Pulmonary hypertension ( ) Vibrio cholerae infection ( ) Cervical carcinoma ( ) Crohn disease ( ) Rhabdomyosarcoma ( ) Berardinelli-Seip congenital lipodystrophy ( ) Asthma ( ) Cardiomyopathy ( ) Catecholaminergic polymorphic ventricular tachycardia 1 ( ) Clear cell renal carcinoma ( ) Cutaneous squamous cell carcinoma ( ) Glioblastoma multiforme ( ) Lipodystrophy ( ) Metastatic prostate carcinoma ( ) Methylmalonic acidemia ( ) Muscular dystrophy ( ) Psoriasis ( )
UniProt ID	CAVN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF15237
Sequence	MEDPTLYIVERPLPGYPDAEAPEPSSAGAQAAEEPSGAGSEELIKSDQVNGVLVLSLLDK IIGAVDQIQLTQAQLEERQAEMEGAVQSIQGELSKLGKAHATTSNTVSKLLEKVRKVSVN VKTVRGSLERQAGQIKKLEVNEAELLRRRNFKVMIYQDEVKLPAKLSISKSLKESEALPE KEGEELGEGERPEEDAAALELSSDEAVEVEEVIEESRAERIKRSGLRRVDDFKKAFSKEK MEKTKVRTRENLEKTRLKTKENLEKTRHTLEKRMNKLGTRLVPAERREKLKTSRDKLRKS FTPDHVVYARSKTAVYKVPPFTFHVKKIREGQVEVLKATEMVEVGADDDEGGAERGEAGD LRRGSSPDVHALLEITEESDAVLVDKSDSD
Function	Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues. Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1). Essential for normal oligomerization of CAV1. Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop. Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template. The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A.
Reactome Pathway	RHOA GTPase cycle (R-HSA-8980692 ) RHOB GTPase cycle (R-HSA-9013026 ) RHOC GTPase cycle (R-HSA-9013106 ) RNA Polymerase I Transcription Termination (R-HSA-73863 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arrhythmia	DISFF2NI	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Congenital generalized lipodystrophy	DIS4XF8N	Strong	Biomarker	[5]
Congenital generalized lipodystrophy type 4	DISH7EAH	Strong	Autosomal recessive	[6]
Ewing sarcoma	DISQYLV3	Strong	Genetic Variation	[7]
Familial partial lipodystrophy	DISFVL9J	Strong	Biomarker	[8]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[3]
Generalized lipodystrophy	DISC6HI8	Strong	Genetic Variation	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[3]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[3]
Liposarcoma	DIS8IZVM	Strong	Biomarker	[11]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[10]
Long QT syndrome	DISMKWS3	Strong	Genetic Variation	[6]
Myopathy	DISOWG27	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
Obesity	DIS47Y1K	Strong	Biomarker	[14]
Prostate cancer	DISF190Y	Strong	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[15]
Pulmonary hypertension	DIS1RSP5	Strong	Biomarker	[16]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[17]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[18]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[19]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[20]
Berardinelli-Seip congenital lipodystrophy	DISKW75N	Supportive	Autosomal recessive	[9]
Asthma	DISW9QNS	Limited	Biomarker	[21]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[5]
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	Limited	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[22]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[23]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[1]
Lipodystrophy	DIS3SGVD	Limited	Genetic Variation	[24]
Metastatic prostate carcinoma	DISVBEZ9	Limited	Altered Expression	[15]
Methylmalonic acidemia	DISHY8VB	Limited	Biomarker	[25]
Muscular dystrophy	DISJD6P7	Limited	Genetic Variation	[24]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[26]
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⏷ Show the Full List of 40 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

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
Topotecan	DMP6G8T	Approved	Caveolae-associated protein 1 (CAVIN1) affects the response to substance of Topotecan.	[49]
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22 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 Caveolae-associated protein 1 (CAVIN1).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Caveolae-associated protein 1 (CAVIN1).	[29]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Caveolae-associated protein 1 (CAVIN1).	[30]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Caveolae-associated protein 1 (CAVIN1).	[31]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[31]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Caveolae-associated protein 1 (CAVIN1).	[32]
Selenium	DM25CGV	Approved	Selenium increases the expression of Caveolae-associated protein 1 (CAVIN1).	[33]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Caveolae-associated protein 1 (CAVIN1).	[34]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Caveolae-associated protein 1 (CAVIN1).	[35]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Caveolae-associated protein 1 (CAVIN1).	[36]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[37]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Caveolae-associated protein 1 (CAVIN1).	[38]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Caveolae-associated protein 1 (CAVIN1).	[39]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Caveolae-associated protein 1 (CAVIN1).	[40]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Caveolae-associated protein 1 (CAVIN1).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Caveolae-associated protein 1 (CAVIN1).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Caveolae-associated protein 1 (CAVIN1).	[42]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[47]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Caveolae-associated protein 1 (CAVIN1).	[48]
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⏷ Show the Full List of 22 Drug(s)

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Caveolae-associated protein 1 (CAVIN1).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Caveolae-associated protein 1 (CAVIN1).	[46]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Caveolae-associated protein 1 (CAVIN1).	[46]
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References

1	Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1.J Neurooncol. 2019 Jun;143(2):207-220. doi: 10.1007/s11060-019-03161-8. Epub 2019 Apr 4.
2	Integrated profiling identifies caveolae-associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients.CNS Neurosci Ther. 2019 Mar;25(3):343-354. doi: 10.1111/cns.13072. Epub 2018 Oct 11.
3	Congenital generalized lipodystrophy: The evaluation of clinical follow-up findings in a series of five patients with type 1 and two patients with type 4.Eur J Med Genet. 2020 Apr;63(4):103819. doi: 10.1016/j.ejmg.2019.103819. Epub 2019 Nov 25.
4	PTRF suppresses the progression of colorectal cancers.Oncotarget. 2017 Jul 25;8(30):48650-48659. doi: 10.18632/oncotarget.9424.
5	Postmortem Findings in a Young Man With Congenital Generalized Lipodystrophy, Type 4 Due to CAVIN1 Mutations.J Clin Endocrinol Metab. 2019 Mar 1;104(3):957-960. doi: 10.1210/jc.2018-01331.
6	Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet. 2010 Mar 12;6(3):e1000874. doi: 10.1371/journal.pgen.1000874.
7	DNA methylation profiling identifies PTRF/Cavin-1 as a novel tumor suppressor in Ewing sarcoma when co-expressed with caveolin-1.Cancer Lett. 2017 Feb 1;386:196-207. doi: 10.1016/j.canlet.2016.11.020. Epub 2016 Nov 25.
8	Clinical review#: Lipodystrophies: genetic and acquired body fat disorders.J Clin Endocrinol Metab. 2011 Nov;96(11):3313-25. doi: 10.1210/jc.2011-1159. Epub 2011 Aug 24.
9	Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. Am J Med Genet A. 2010 Sep;152A(9):2245-53. doi: 10.1002/ajmg.a.33578.
10	Increases in endothelial caveolin-1 and cavins correlate with cirrhosis progression.Micron. 2015 Sep;76:52-61. doi: 10.1016/j.micron.2015.03.009. Epub 2015 Mar 31.
11	Focus on the role of Caveolin and Cavin protein families in liposarcoma.Differentiation. 2017 Mar-Apr;94:21-26. doi: 10.1016/j.diff.2016.11.007. Epub 2016 Dec 8.
12	The role of PTRF/Cavin1 as a biomarker in both glioma and serum exosomes.Theranostics. 2018 Feb 7;8(6):1540-1557. doi: 10.7150/thno.22952. eCollection 2018.
13	PTRF/cavin-1 and MIF proteins are identified as non-small cell lung cancer biomarkers by label-free proteomics.PLoS One. 2012;7(3):e33752. doi: 10.1371/journal.pone.0033752. Epub 2012 Mar 26.
14	Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.FASEB J. 2014 Aug;28(8):3769-79. doi: 10.1096/fj.14-251165. Epub 2014 May 8.
15	Galectin-3 Overrides PTRF/Cavin-1 Reduction of PC3 Prostate Cancer Cell Migration.PLoS One. 2015 May 5;10(5):e0126056. doi: 10.1371/journal.pone.0126056. eCollection 2015.
16	Elevated pulmonary arterial pressure and altered expression of Ddah1 and Arg1 in mice lacking cavin-1/PTRF.Physiol Rep. 2013 Jun;1(1):e00008. doi: 10.1002/PHY2.8. Epub 2013 Jun 7.
17	PTRF/cavin-1 is essential for multidrug resistance in cancer cells.J Proteome Res. 2013 Feb 1;12(2):605-14. doi: 10.1021/pr300651m. Epub 2013 Jan 4.
18	A tumor-associated glycosylation change in the glucose transporter GLUT1 controlled by tumor suppressor function in human cell hybrids.J Cell Sci. 1995 Dec;108 ( Pt 12):3735-43. doi: 10.1242/jcs.108.12.3735.
19	Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.Nat Genet. 2010 Dec;42(12):1118-25. doi: 10.1038/ng.717.
20	Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma.Lab Invest. 2015 Jun;95(6):585-602. doi: 10.1038/labinvest.2015.45. Epub 2015 Mar 30.
21	Dephosphorylated Polymerase I and Transcript Release Factor Prevents Allergic Asthma Exacerbations by Limiting IL-33 Release.Front Immunol. 2018 Jun 21;9:1422. doi: 10.3389/fimmu.2018.01422. eCollection 2018.
22	PTRF/CAVIN1, regulated by SHC1 through the EGFR pathway, is found in urine exosomes as a potential biomarker of ccRCC.Carcinogenesis. 2020 May 14;41(3):274-283. doi: 10.1093/carcin/bgz147.
23	MiR-217 promotes cutaneous squamous cell carcinoma progression by targeting PTRF.Am J Transl Res. 2017 Feb 15;9(2):647-655. eCollection 2017.
24	Interaction of cavin-1/PTRF leucine zipper domain 2 and its congenitalgeneralizedlipodystrophy mutant with model membranes.Biochem Biophys Res Commun. 2020 Jan 15;521(3):732-738. doi: 10.1016/j.bbrc.2019.10.167. Epub 2019 Nov 7.
25	Quantitative analysis of mitochondrial protein expression in methylmalonic acidemia by two-dimensional difference gel electrophoresis.J Proteome Res. 2006 Jul;5(7):1602-10. doi: 10.1021/pr050481r.
26	Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.Nat Commun. 2015 Apr 23;6:6916. doi: 10.1038/ncomms7916.
27	The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
28	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
29	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.
30	Polymerase I and transcript release factor (PTRF)/cavin-1 is a novel regulator of stress-induced premature senescence. J Biol Chem. 2011 Aug 19;286(33):28657-28661. doi: 10.1074/jbc.C111.235119. Epub 2011 Jun 24.
31	Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
32	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.
33	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.
34	Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
35	Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
36	Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
37	Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
38	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
39	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
40	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
41	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
42	CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
43	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
44	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.
45	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
46	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.
47	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.
48	Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
49	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.