Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOLBK79)

• DOT Name: Caveolae-associated protein 3 (CAVIN3)
• Synonyms: Cavin-3; Protein kinase C delta-binding protein; Serum deprivation response factor-related gene product that binds to C-kinase; hSRBC
• Gene Name: CAVIN3
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Depression
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Gastric neoplasm
  Hepatitis C virus infection
  Inflammatory bowel disease
  Liver cirrhosis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Major depressive disorder
  Metabolic disorder
  Neoplasm
  Stomach cancer
  Ulcerative colitis
  Breast cancer
  Breast carcinoma
  Neuroblastoma
• UniProt ID: CAVN3_HUMAN
• Pfam ID: PF15237
• Sequence:
  MRESALERGPVPEAPAGGPVHAVTVVTLLEKLASMLETLRERQGGLARRQGGLAGSVRRI
  QSGLGALSRSHDTTSNTLAQLLAKAERVSSHANAAQERAVRRAAQVQRLEANHGLLVARG
  KLHVLLFKEEGEVPASAFQKAPEPLGPADQSELGPEQLEAEVGESSDEEPVESRAQRLRR
  TGLQKVQSLRRALSGRKGPAAPPPTPVKPPRLGPGRSAEAQPEAQPALEPTLEPEPPQDT
  EEDPGRPGAAEEALLQMESVA
• Function: Regulates the traffic and/or budding of caveolae. Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in smooth muscle but not in the lung and heart endothelial cells. Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by promoting the rapid release of caveolae from the cell surface. Plays a role in the regulation of the circadian clock. Modulates the period length and phase of circadian gene expression and also regulates expression and interaction of the core clock components PER1/2 and CRY1/2.
• Tissue Specificity: Skeletal muscle, liver, stomach, lung, kidney and heart (at protein level). Strongly expressed in mammary and epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[2]
Depression	DIS3XJ69	Strong	Genetic Variation	[3]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[4]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[4]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[1]
Gastric neoplasm	DISOKN4Y	Strong	Posttranslational Modification	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[5]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[6]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[5]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Altered Expression	[8]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[8]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[8]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[3]
Metabolic disorder	DIS71G5H	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[1]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[10]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[10]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[11]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Caveolae-associated protein 3 (CAVIN3) affects the response to substance of Mitoxantrone.	[24]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Caveolae-associated protein 3 (CAVIN3).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Caveolae-associated protein 3 (CAVIN3).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[18]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Caveolae-associated protein 3 (CAVIN3).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Caveolae-associated protein 3 (CAVIN3).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Caveolae-associated protein 3 (CAVIN3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Caveolae-associated protein 3 (CAVIN3).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Caveolae-associated protein 3 (CAVIN3).	[22]

References

• [1] Frequent epigenetic inactivation of hSRBC in gastric cancer and its implication in attenuated p53 response to stresses.Int J Cancer. 2008 Apr 1;122(7):1573-84. doi: 10.1002/ijc.23166.
• [2] Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer.J Natl Cancer Inst. 2014 Jan;106(1):djt322. doi: 10.1093/jnci/djt322. Epub 2013 Nov 22.
• [3] PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder.J Affect Disord. 2017 Jan 1;207:136-140. doi: 10.1016/j.jad.2016.09.034. Epub 2016 Sep 28.
• [4] Genetic polymorphism of PRKCDBP is associated with an increased risk of endometrial cancer.Cancer Invest. 2012 Nov;30(9):642-5. doi: 10.3109/07357907.2012.727054. Epub 2012 Sep 28.
• [5] 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.
• [6] Elevation of PRKCDBP, a novel transcriptional target of TNF-, and its downregulation by infliximab in patients with ulcerative colitis.Dig Dis Sci. 2014 Dec;59(12):2947-57. doi: 10.1007/s10620-014-3282-4. Epub 2014 Jul 23.
• [7] ROR1-CAVIN3 interaction required for caveolae-dependent endocytosis and pro-survival signaling in lung adenocarcinoma.Oncogene. 2019 Jun;38(26):5142-5157. doi: 10.1038/s41388-019-0785-7. Epub 2019 Mar 20.
• [8] Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation.Oncogene. 2005 Sep 15;24(41):6249-55. doi: 10.1038/sj.onc.1208775.
• [9] CRY1, CRY2 and PRKCDBP genetic variants in metabolic syndrome.Hypertens Res. 2015 Mar;38(3):186-92. doi: 10.1038/hr.2014.157. Epub 2014 Nov 13.
• [10] Clinical relevance of loss of 11p15 in primary and metastatic breast cancer: association with loss of PRKCDBP expression in brain metastases.PLoS One. 2012;7(10):e47537. doi: 10.1371/journal.pone.0047537. Epub 2012 Oct 31.
• [11] Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma.BMC Cancer. 2011 Feb 11;11:66. doi: 10.1186/1471-2407-11-66.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [17] 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.
• [18] 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.
• [19] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [20] 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.
• [21] 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.
• [22] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [24] 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.