Details of Drug Off-Target (DOT)

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

• DOT Name: Protein orai-2 (ORAI2)
• Synonyms: CAP-binding protein complex-interacting protein 2; Transmembrane protein 142B
• Gene Name: ORAI2
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
• UniProt ID: ORAI2_HUMAN
• Pfam ID: PF07856
• Sequence:
  MSAELNVPIDPSAPACPEPGHKGMDYRDWVRRSYLELVTSNHHSVQALSWRKLYLSRAKL
  KASSRTSALLSGFAMVAMVEVQLETQYQYPRPLLIAFSACTTVLVAVHLFALLISTCILP
  NVEAVSNIHNLNSISESPHERMHPYIELAWGFSTVLGILLFLAEVVLLCWIKFLPVDARR
  QPGPPPGPGSHTGWQAALVSTIIMVPVGLIFVVFTIHFYRSLVRHKTERHNREIEELHKL
  KVQLDGHERSLQVL
• Function: Ca(2+) release-activated Ca(2+)-like (CRAC-like) channel subunit which mediates Ca(2+) influx and increase in Ca(2+)-selective current by synergy with the Ca(2+) sensor, STIM1.
• KEGG Pathway: Calcium sig.ling pathway (hsa04020)
• Reactome Pathway:
  Ion homeostasis (R-HSA-5578775)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  Elevation of cytosolic Ca2+ levels (R-HSA-139853)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]

3 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 Protein orai-2 (ORAI2).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein orai-2 (ORAI2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein orai-2 (ORAI2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein orai-2 (ORAI2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein orai-2 (ORAI2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein orai-2 (ORAI2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein orai-2 (ORAI2).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Protein orai-2 (ORAI2).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein orai-2 (ORAI2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein orai-2 (ORAI2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein orai-2 (ORAI2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein orai-2 (ORAI2).	[13]

References

• [1] Identification of Key Pathways and Genes in the Orai2 Mediated Classical and Mesenchymal Subtype of Glioblastoma by Bioinformatic Analyses.Dis Markers. 2019 Oct 20;2019:7049294. doi: 10.1155/2019/7049294. eCollection 2019.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] 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.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.