Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV42SIT)

• DOT Name: Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1)
• Synonyms: CAB1; Calcium channel voltage-dependent subunit beta 1
• Gene Name: CACNB1
• Related Disease:
  Colon cancer
  Colon carcinoma
  Acute myelogenous leukaemia
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: CACB1_HUMAN
• PDB ID: 7VFS; 7VFU; 7VFV; 7VFW; 7XLQ; 7YG5
• Pfam ID: PF00625 ; PF12052
• Sequence:
  MVQKTSMSRGPYPPSQEIPMEVFDPSPQGKYSKRKGRFKRSDGSTSSDTTSNSFVRQGSA
  ESYTSRPSDSDVSLEEDREALRKEAERQALAQLEKAKTKPVAFAVRTNVGYNPSPGDEVP
  VQGVAITFEPKDFLHIKEKYNNDWWIGRLVKEGCEVGFIPSPVKLDSLRLLQEQKLRQNR
  LGSSKSGDNSSSSLGDVVTGTRRPTPPASAKQKQKSTEHVPPYDVVPSMRPIILVGPSLK
  GYEVTDMMQKALFDFLKHRFDGRISITRVTADISLAKRSVLNNPSKHIIIERSNTRSSLA
  EVQSEIERIFELARTLQLVALDADTINHPAQLSKTSLAPIIVYIKITSPKVLQRLIKSRG
  KSQSKHLNVQIAASEKLAQCPPEMFDIILDENQLEDACEHLAEYLEAYWKATHPPSSTPP
  NPLLNRTMATAALAASPAPVSNLQGPYLASGDQPLERATGEHASMHEYPGELGQPPGLYP
  SSHPPGRAGTLRALSRQDTFDADTPGSRNSAYTELGDSCVDMETDPSEGPGLGDPAGGGT
  PPARQGSWEDEEEDYEEELTDNRNRGRNKARYCAEGGGPVLGRNKNELEGWGRGVYIR
• Function: Regulatory subunit of L-type calcium channels. Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit. Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane. Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit. Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit.
• Tissue Specificity: Detected in heart ventricle (at protein level) . Isoform 1 and isoform 3 are expressed in brain, heart, spleen, central nervous system and neuroblastoma cells. Isoform 2 is expressed in skeletal muscle.
• 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:
  NCAM1 interactions (R-HSA-419037)
  Phase 0 - rapid depolarisation (R-HSA-5576892)
  Phase 2 - plateau phase (R-HSA-5576893)
  Presynaptic depolarization and calcium channel opening (R-HSA-112308)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[3]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[5]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[11]

1 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 increases the methylation of Voltage-dependent L-type calcium channel subunit beta-1 (CACNB1).	[8]

References

• [1] Integrated analysis of gene expression signatures associated with colon cancer from three datasets.Gene. 2018 May 15;654:95-102. doi: 10.1016/j.gene.2018.02.007. Epub 2018 Feb 3.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Distribution of microsatellite instability in Danish ovarian tumor patients and the prognostic value in ovarian cancer patients.Oncol Res. 2008;17(1):43-9. doi: 10.3727/096504008784046090.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.