Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJMZD2T)

DOT Name	Calcyclin-binding protein (CACYBP)
Synonyms	CacyBP; hCacyBP; S100A6-binding protein; Siah-interacting protein
Gene Name	CACYBP
Related Disease	Pancreatic cancer ( ) Advanced cancer ( ) Alzheimer disease ( ) Anxiety ( ) Anxiety disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Depression ( ) Dilated cardiomyopathy 1A ( ) Endometriosis ( ) Gastric cancer ( ) Gastric neoplasm ( ) Glioma ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Kidney cancer ( ) Kidney neoplasm ( ) Neoplasm ( ) Pancreatic tumour ( ) Parkinson disease ( ) Renal carcinoma ( ) Renal cell carcinoma ( ) Stomach cancer ( ) Type-1/2 diabetes ( ) Varicose veins ( ) Major depressive disorder ( ) Melanoma ( ) Cardiomyopathy ( ) Colon cancer ( ) Colon carcinoma ( ) Dermatomyositis ( ) Generalized anxiety disorder ( ) Metastatic malignant neoplasm ( ) Myocardial infarction ( ) Neuroblastoma ( ) Small lymphocytic lymphoma ( ) Stroke ( )
UniProt ID	CYBP_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1X5M; 2A25; 2A26
Pfam ID	PF04969 ; PF05002 ; PF09032
Sequence	MASEELQKDLEEVKVLLEKATRKRVRDALTAEKSKIETEIKNKMQQKSQKKAELLDNEKP AAVVAPITTGYTVKISNYGWDQSDKFVKIYITLTGVHQVPTENVQVHFTERSFDLLVKNL NGKSYSMIVNNLLKPISVEGSSKKVKTDTVLILCRKKVENTRWDYLTQVEKECKEKEKPS YDTETDPSEGLMNVLKKIYEDGDDDMKRTINKAWVESREKQAKGDTEF
Function	May be involved in calcium-dependent ubiquitination and subsequent proteasomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1).
KEGG Pathway	Wnt sig.ling pathway (hsa04310 )

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Pancreatic cancer	DISJC981	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Anxiety	DISIJDBA	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[6]
Endometriosis	DISX1AG8	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Kidney cancer	DISBIPKM	Strong	Biomarker	[13]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[13]
Parkinson disease	DISQVHKL	Strong	Biomarker	[3]
Renal carcinoma	DISER9XT	Strong	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[15]
Varicose veins	DISIMBN2	Strong	Biomarker	[16]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[17]
Melanoma	DIS1RRCY	moderate	Biomarker	[18]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[19]
Colon cancer	DISVC52G	Limited	Biomarker	[7]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[7]
Dermatomyositis	DIS50C5O	Limited	Biomarker	[20]
Generalized anxiety disorder	DISPSQCW	Limited	Genetic Variation	[17]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[21]
Myocardial infarction	DIS655KI	Limited	Biomarker	[22]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[23]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[24]
Stroke	DISX6UHX	Limited	Biomarker	[25]
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⏷ Show the Full List of 39 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
Doxorubicin	DMVP5YE	Approved	Calcyclin-binding protein (CACYBP) decreases the response to substance of Doxorubicin.	[45]
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19 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 Calcyclin-binding protein (CACYBP).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Calcyclin-binding protein (CACYBP).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calcyclin-binding protein (CACYBP).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calcyclin-binding protein (CACYBP).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Calcyclin-binding protein (CACYBP).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Calcyclin-binding protein (CACYBP).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calcyclin-binding protein (CACYBP).	[32]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Calcyclin-binding protein (CACYBP).	[33]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calcyclin-binding protein (CACYBP).	[34]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Calcyclin-binding protein (CACYBP).	[35]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Calcyclin-binding protein (CACYBP).	[36]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Calcyclin-binding protein (CACYBP).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Calcyclin-binding protein (CACYBP).	[38]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Calcyclin-binding protein (CACYBP).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Calcyclin-binding protein (CACYBP).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Calcyclin-binding protein (CACYBP).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Calcyclin-binding protein (CACYBP).	[42]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Calcyclin-binding protein (CACYBP).	[43]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Calcyclin-binding protein (CACYBP).	[44]
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⏷ Show the Full List of 19 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Calcyclin-binding protein (CACYBP).	[39]
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References

1	CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2.Apoptosis. 2013 Jul;18(7):861-9. doi: 10.1007/s10495-013-0831-9.
2	CACYBP Enhances Cytoplasmic Retention of P27(Kip1) to Promote Hepatocellular Carcinoma Progression in the Absence of RNF41 Mediated Degradation.Theranostics. 2019 Oct 22;9(26):8392-8408. doi: 10.7150/thno.36838. eCollection 2019.
3	Unveiling the olfactory proteostatic disarrangement in Parkinson's disease by proteome-wide profiling.Neurobiol Aging. 2019 Jan;73:123-134. doi: 10.1016/j.neurobiolaging.2018.09.018. Epub 2018 Sep 25.
4	Anxiety, Depression, and Pain Symptoms: Associations With the Course of Marijuana Use and Drug Use Consequences Among Urban Primary Care Patients.J Addict Med. 2018 Jan/Feb;12(1):45-52. doi: 10.1097/ADM.0000000000000362.
5	TGF- drives epithelial-mesenchymal transition through EF1-mediated downregulation of ESRP.Oncogene. 2012 Jun 28;31(26):3190-201. doi: 10.1038/onc.2011.493. Epub 2011 Oct 31.
6	Down-regulation of CacyBP is associated with poor prognosis and the effects on COX-2 expression in breast cancer.Int J Oncol. 2010 Nov;37(5):1261-9. doi: 10.3892/ijo_00000777.
7	The effect of S100A6 on nuclear translocation of CacyBP/SIP in colon cancer cells.PLoS One. 2018 Mar 13;13(3):e0192208. doi: 10.1371/journal.pone.0192208. eCollection 2018.
8	Upregulation of S100A6 in patients with endometriosis and its role in ectopic endometrial stromal cells.Gynecol Endocrinol. 2018 Sep;34(9):815-820. doi: 10.1080/09513590.2018.1451506. Epub 2018 Mar 16.
9	CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells.World J Gastroenterol. 2016 Apr 21;22(15):3992-4001. doi: 10.3748/wjg.v22.i15.3992.
10	Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer.Mol Cancer Res. 2007 Dec;5(12):1254-62. doi: 10.1158/1541-7786.MCR-06-0426.
11	CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells through activating Siah1 mediated ubiquitination and degradation of cytoplasmic p27.Cell Biol Int. 2018 Feb;42(2):216-226. doi: 10.1002/cbin.10889. Epub 2017 Nov 15.
12	Bayesian analysis of complex interacting mutations in HIV drug resistance and cross-resistance.Adv Exp Med Biol. 2015;827:367-83. doi: 10.1007/978-94-017-9245-5_22.
13	Expression and clinical significance of CacyBP/SIP in pancreatic cancer.Pancreatology. 2008;8(4-5):470-7. doi: 10.1159/000151774. Epub 2008 Sep 3.
14	Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma.Biochem Biophys Res Commun. 2007 May 18;356(4):864-71. doi: 10.1016/j.bbrc.2007.03.080. Epub 2007 Mar 26.
15	Nitric oxide and its role as a non-adrenergic, non-cholinergic inhibitory neurotransmitter in the gastrointestinal tract.Br J Pharmacol. 2019 Jan;176(2):212-227. doi: 10.1111/bph.14459. Epub 2018 Sep 3.
16	Inhibitory Neural Regulation of the Ca (2+) Transients in Intramuscular Interstitial Cells of Cajal in the Small Intestine.Front Physiol. 2018 Apr 9;9:328. doi: 10.3389/fphys.2018.00328. eCollection 2018.
17	Is the effect of work-related psychosocial exposure on depressive and anxiety disorders short-term, lagged or cumulative?.Int Arch Occup Environ Health. 2020 Jan;93(1):87-104. doi: 10.1007/s00420-019-01466-9. Epub 2019 Aug 3.
18	Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink.Carbohydr Polym. 2013 Jan 2;91(1):403-9. doi: 10.1016/j.carbpol.2012.08.050. Epub 2012 Aug 22.
19	Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.Mol Genet Genomics. 2012 Apr;287(4):351-60. doi: 10.1007/s00438-012-0684-x. Epub 2012 Mar 8.
20	Efficacy and safety of oral high-trough level tacrolimus in acute/subacute interstitial pneumonia with dermatomyositis.Int J Rheum Dis. 2019 Feb;22(2):303-313. doi: 10.1111/1756-185X.13414. Epub 2018 Nov 5.
21	Sulfated polysaccharide of Sepiella Maindroni ink inhibits the migration, invasion and matrix metalloproteinase-2 expression through suppressing EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells.Int J Biol Macromol. 2018 Feb;107(Pt A):349-362. doi: 10.1016/j.ijbiomac.2017.08.178. Epub 2017 Sep 9.
22	Calcyclin binding protein promotes DNA synthesis and differentiation in rat neonatal cardiomyocytes.J Cell Biochem. 2006 Jun 1;98(3):555-66. doi: 10.1002/jcb.20710.
23	CacyBP/SIP phosphatase activity in neuroblastoma NB2a and colon cancer HCT116 cells.Biochem Cell Biol. 2012 Aug;90(4):558-64. doi: 10.1139/o2012-011. Epub 2012 Apr 5.
24	Expression and regulation of CacyBP/SIP in chronic lymphocytic leukemia cell balances of cell proliferation with apoptosis.J Cancer Res Clin Oncol. 2016 Apr;142(4):741-8. doi: 10.1007/s00432-015-2077-0. Epub 2015 Nov 25.
25	Effects of virtual reality-based training with BTs-Nirvana on functional recovery in stroke patients: preliminary considerations.Int J Neurosci. 2018 Sep;128(9):791-796. doi: 10.1080/00207454.2017.1403915. Epub 2018 Feb 2.
26	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.
27	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
28	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.
29	Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
30	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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	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.
33	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
34	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
35	Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
36	Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
37	Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
38	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.
39	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.
40	Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
41	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.
42	Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
43	Integrated analysis of paraquat-induced microRNAs-mRNAs changes in human neural progenitor cells. Toxicol In Vitro. 2017 Oct;44:196-205. doi: 10.1016/j.tiv.2017.06.010. Epub 2017 Jun 12.
44	Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.
45	Nuclear proteomics with XRCC3 knockdown to reveal the development of doxorubicin-resistant uterine cancer. Toxicol Sci. 2014 Jun;139(2):396-406. doi: 10.1093/toxsci/kfu051. Epub 2014 Mar 27.