Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDLEJ4T)

• DOT Name: Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC)
• Gene Name: HRC
• UniProt ID: SRCH_HUMAN
• Pfam ID: PF10529
• Sequence:
  MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAGLSEEASAELRHH
  LHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVSKEYGHLLPGHRSQDHKVGDEGVSG
  EEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPSHRSHSHQDEDEDEVVSSEHHHHILRH
  GHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRH
  QGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH
  EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTE
  RWHQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHH
  RVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMSHHPPGHTVVKDRSHLRKD
  DSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDK
  EEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA
  SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQHCQ
  FCYLCPLVCETVCAPGSYVDYFSSSLYQALADMLETPEP
• Function: May play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Cardiac muscle contraction (hsa04260)
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[2]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[4]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[5]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[1]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[1]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[9]

2 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 Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sarcoplasmic reticulum histidine-rich calcium-binding protein (HRC).	[8]

References

• [1] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.
• [9] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.