Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTPKW9G)

• DOT Name: Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP)
• Gene Name: CBARP
• UniProt ID: CBARP_HUMAN
• Sequence:
  MQPTATMATAATTTTTTTATVALTTSWDNATGRPTAEPDPILDNYVLLVVVMSLFVGGTL
  VVLSGVLLLCKRCWDVHQRLNRAMEEAEKTTTTYLDNGTHPAQDPDFRGEDPECQDAETE
  RFLSTSSTGRRVSFNEAALFEQSRKTQDKGRRYTLTEGDFHHLKNARLTHLHLPPLKIVT
  IHECDSGEASSATTPHPATSPKATLAIFQPPGKALTGRSVGPSSALPGDPYNSAAGATDF
  AEISPSASSDSGEGTSLDAGTRSTKAGGPGAAAGPGEAGPGSGAGTVLQFLTRLRRHASL
  DGASPYFKVKKWKLEPSQRAASLDTRGSPKRHHFQRQRAASESTEQEEGDAPQEDFIQYI
  ARAGDAVAFPHPRPFLASPPPALGRLEAAEAAGGASPDSPPERGAGSAGPEQQQPPLEPD
  AERDAGPEQAQTSYRDLWSLRASLELHAAASDHSSSGNDRDSVRSGDSSGSGSGGAAPAF
  PPPSPPAPRPKDGEARRLLQMDSGYASIEGRGAGDDTEPPAAPARPRSPRAWPRRPRRDY
  SIDEKTDALFHEFLRHDPHFDDTPAAARHRARAHPHARKQWQRGRQHSDPGARAAPALAG
  TPAPPAGAARPARAPLRRGDSVDGPPDGRTLGGAGDDPAIPVIEEEPGGGGCPGSGLCVL
  PSGSVLDKLAAGLDERLFPPRLAEPVVATPALVAAAPTSPDHSPA
• Function: Negatively regulates voltage-gated calcium channels by preventing the interaction between their alpha and beta subunits. Thereby, negatively regulates calcium channels activity at the plasma membrane and indirectly inhibits calcium-regulated exocytosis.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP).	[7]

References

• [1] 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.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] 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.