Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8L843R)

• DOT Name: EF-hand calcium-binding domain-containing protein 4A (CRACR2B)
• Synonyms: Calcium release-activated calcium channel regulator 2B; CRAC channel regulator 2B; Calcium release-activated channel regulator 2B
• Gene Name: CRACR2B
• Related Disease:
  Chronic obstructive pulmonary disease
  Chronic bronchitis
• UniProt ID: EFC4A_HUMAN
• Sequence:
  MASPGKPGADEAQEEEGELEGGSAGPRAAILEQAEELFLLCDKEAKGFITKHDLQGLQSD
  LPLTPEQLEAVFESLDRAHTGFLTAREFCLGLGMFVGVASAQGANPCRTPEETFESGGLD
  VQGTAGSLDEEEEEEERFHTVLEQLGVAPVLGKQRAVRTLWARLQRERPELLGSFEDVLI
  RASACLEEAARERDGLEQALRRRESEHEREVRALYEETEQLREQSRRPPSQNFARGERRS
  RLELELQSREQDLERAGLRQRELEQQLHAQAAEHLEAQAQNSQLWRAHEALRTQLEGAQE
  QIRRLESEARGRQEQTQRDVVAVSRNMQKEKVSLLRQLELLRELNTRLRDDRDACEARRA
  GSSCRKALTTARLPGPTCCCCCCWARPPRRGSGHLPSAR
• Function: Plays a role in store-operated Ca(2+) entry (SOCE).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]
Chronic bronchitis	DISS8O8V	Limited	Biomarker	[1]

2 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 EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[8]
Aspirin	DM672AH	Approved	Aspirin increases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[9]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[12]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of EF-hand calcium-binding domain-containing protein 4A (CRACR2B).	[13]

References

• [1] Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respir Res. 2014 Sep 21;15(1):113. doi: 10.1186/s12931-014-0113-2.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [10] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.