Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP30DIU)

DOT Name Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3)
Synonyms CAB3; Calcium channel voltage-dependent subunit beta 3
Gene Name CACNB3
Related Disease
Bipolar disorder ( )
Neoplasm ( )
Thrombocytopenia ( )
Long QT syndrome ( )
Non-insulin dependent diabetes ( )
UniProt ID
CACB3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7MIX; 7MIY; 7UHF; 7UHG; 8E59; 8E5A; 8E5B; 8EPL; 8WE6; 8WE7; 8WE8; 8WE9
Pfam ID
PF00625 ; PF12052
Sequence
MYDDSYVPGFEDSEAGSADSYTSRPSLDSDVSLEEDRESARREVESQAQQQLERAKHKPV
AFAVRTNVSYCGVLDEECPVQGSGVNFEAKDFLHIKEKYSNDWWIGRLVKEGGDIAFIPS
PQRLESIRLKQEQKARRSGNPSSLSDIGNRRSPPPSLAKQKQKQAEHVPPYDVVPSMRPV
VLVGPSLKGYEVTDMMQKALFDFLKHRFDGRISITRVTADLSLAKRSVLNNPGKRTIIER
SSARSSIAEVQSEIERIFELAKSLQLVVLDADTINHPAQLAKTSLAPIIVFVKVSSPKVL
QRLIRSRGKSQMKHLTVQMMAYDKLVQCPPESFDVILDENQLEDACEHLAEYLEVYWRAT
HHPAPGPGLLGPPSAIPGLQNQQLLGERGEEHSPLERDSLMPSDEASESSRQAWTGSSQR
SSRHLEEDYADAYQDLYQPHRQHTSGLPSANGHDPQDRLLAQDSEHNHSDRNWQRNRPWP
KDSY
Function
Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Increases CACNA1B peak calcium current and shifts the voltage dependencies of channel activation and inactivation. Increases CACNA1C peak calcium current and shifts the voltage dependencies of channel activation and inactivation.
Tissue Specificity Expressed mostly in brain, colon and ovary.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Cardiac muscle contraction (hsa04260 )
Adrenergic sig.ling in cardiomyocytes (hsa04261 )
Oxytocin sig.ling pathway (hsa04921 )
Hypertrophic cardiomyopathy (hsa05410 )
Arrhythmogenic right ventricular cardiomyopathy (hsa05412 )
Dilated cardiomyopathy (hsa05414 )
Reactome Pathway
Adrenaline,noradrenaline inhibits insulin secretion (R-HSA-400042 )
NCAM1 interactions (R-HSA-419037 )
Regulation of insulin secretion (R-HSA-422356 )
Presynaptic depolarization and calcium channel opening (R-HSA-112308 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bipolar disorder DISAM7J2 Strong Biomarker [1]
Neoplasm DISZKGEW Strong Altered Expression [2]
Thrombocytopenia DISU61YW Strong Biomarker [3]
Long QT syndrome DISMKWS3 Limited Biomarker [4]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [6]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [7]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [9]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Voltage-dependent L-type calcium channel subunit beta-3 (CACNB3). [10]
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⏷ Show the Full List of 7 Drug(s)

References

1 Calcium channel genes associated with bipolar disorder modulate lithium's amplification of circadian rhythms.Neuropharmacology. 2016 Feb;101:439-48. doi: 10.1016/j.neuropharm.2015.10.017. Epub 2015 Oct 22.
2 Prediction of postoperative recurrence-free survival in non-small cell lung cancer by using an internationally validated gene expression model.Clin Cancer Res. 2011 May 1;17(9):2934-46. doi: 10.1158/1078-0432.CCR-10-1803. Epub 2011 Jan 17.
3 The IIb p.Leu841Met (Cab3(a+) ) polymorphism results in a new human platelet alloantigen involved in neonatal alloimmune thrombocytopenia.Transfusion. 2013 Mar;53(3):554-63. doi: 10.1111/j.1537-2995.2012.03762.x. Epub 2012 Jun 28.
4 The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes.Genomics. 1995 May 20;27(2):312-9. doi: 10.1006/geno.1995.1048.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 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.
7 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
8 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.
9 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.
10 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.