Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYNXAW0)

DOT Name Stromal interaction molecule 2 (STIM2)
Gene Name STIM2
Related Disease
Advanced cancer ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Glioblastoma multiforme ( )
Alzheimer disease ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Depression ( )
Dermatitis ( )
Huntington disease ( )
leukaemia ( )
Leukemia ( )
Lymphoproliferative syndrome ( )
Primary myelofibrosis ( )
Pulmonary arterial hypertension ( )
T-cell acute lymphoblastic leukaemia ( )
Breast neoplasm ( )
Melanoma ( )
Type-1 diabetes ( )
Acute myelogenous leukaemia ( )
Neoplasm ( )
Neuroblastoma ( )
UniProt ID
STIM2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2L5Y
Pfam ID
PF07647 ; PF16533
Sequence
MLVLGLLVAGAADGCELVPRHLRGRRATGSAATAASSPAAAAGDSPALMTDPCMSLSPPC
FTEEDRFSLEALQTIHKQMDDDKDGGIEVEESDEFIREDMKYKDATNKHSHLHREDKHIT
IEDLWKRWKTSEVHNWTLEDTLQWLIEFVELPQYEKNFRDNNVKGTTLPRIAVHEPSFMI
SQLKISDRSHRQKLQLKALDVVLFGPLTRPPHNWMKDFILTVSIVIGVGGCWFAYTQNKT
SKEHVAKMMKDLESLQTAEQSLMDLQERLEKAQEENRNVAVEKQNLERKMMDEINYAKEE
ACRLRELREGAECELSRRQYAEQELEQVRMALKKAEKEFELRSSWSVPDALQKWLQLTHE
VEVQYYNIKRQNAEMQLAIAKDEAEKIKKKRSTVFGTLHVAHSSSLDEVDHKILEAKKAL
SELTTCLRERLFRWQQIEKICGFQIAHNSGLPSLTSSLYSDHSWVVMPRVSIPPYPIAGG
VDDLDEDTPPIVSQFPGTMAKPPGSLARSSSLCRSRRSIVPSSPQPQRAQLAPHAPHPSH
PRHPHHPQHTPHSLPSPDPDILSVSSCPALYRNEEEEEAIYFSAEKQWEVPDTASECDSL
NSSIGRKQSPPLSLEIYQTLSPRKISRDEVSLEDSSRGDSPVTVDVSWGSPDCVGLTETK
SMIFSPASKVYNGILEKSCSMNQLSSGIPVPKPRHTSCSSAGNDSKPVQEAPSVARISSI
PHDLCHNGEKSKKPSKIKSLFKKKSK
Function
Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx.
Tissue Specificity Expressed in all tissues and tumor cell lines examined.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Colon cancer DISVC52G Definitive Altered Expression [2]
Colon carcinoma DISJYKUO Definitive Altered Expression [2]
Colorectal carcinoma DIS5PYL0 Definitive Altered Expression [2]
Colorectal neoplasm DISR1UCN Definitive Altered Expression [2]
Glioblastoma multiforme DISK8246 Definitive Biomarker [2]
Alzheimer disease DISF8S70 Strong Altered Expression [3]
Autoimmune disease DISORMTM Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [4]
Breast carcinoma DIS2UE88 Strong Biomarker [4]
Depression DIS3XJ69 Strong Biomarker [5]
Dermatitis DISY5SZC Strong Biomarker [6]
Huntington disease DISQPLA4 Strong Altered Expression [3]
leukaemia DISS7D1V Strong Biomarker [7]
Leukemia DISNAKFL Strong Biomarker [7]
Lymphoproliferative syndrome DISMVL8O Strong Biomarker [6]
Primary myelofibrosis DIS6L0CN Strong Altered Expression [8]
Pulmonary arterial hypertension DISP8ZX5 Strong Biomarker [9]
T-cell acute lymphoblastic leukaemia DIS17AI2 Strong Biomarker [7]
Breast neoplasm DISNGJLM moderate Biomarker [4]
Melanoma DIS1RRCY moderate Biomarker [10]
Type-1 diabetes DIS7HLUB Disputed Biomarker [11]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [12]
Neoplasm DISZKGEW Limited Altered Expression [10]
Neuroblastoma DISVZBI4 Limited Altered Expression [13]
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⏷ Show the Full List of 25 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Stromal interaction molecule 2 (STIM2). [14]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Stromal interaction molecule 2 (STIM2). [15]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Stromal interaction molecule 2 (STIM2). [16]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Stromal interaction molecule 2 (STIM2). [17]
Quercetin DM3NC4M Approved Quercetin affects the expression of Stromal interaction molecule 2 (STIM2). [19]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Stromal interaction molecule 2 (STIM2). [20]
Bortezomib DMNO38U Approved Bortezomib decreases the expression of Stromal interaction molecule 2 (STIM2). [21]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Stromal interaction molecule 2 (STIM2). [22]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Stromal interaction molecule 2 (STIM2). [19]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Stromal interaction molecule 2 (STIM2). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Stromal interaction molecule 2 (STIM2). [25]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Stromal interaction molecule 2 (STIM2). [26]
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⏷ Show the Full List of 12 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Stromal interaction molecule 2 (STIM2). [18]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Stromal interaction molecule 2 (STIM2). [24]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Stromal interaction molecule 2 (STIM2). [24]
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References

1 Role of STIM2 in cell function and physiopathology.J Physiol. 2017 May 15;595(10):3111-3128. doi: 10.1113/JP273889. Epub 2017 Feb 19.
2 Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype.Mol Carcinog. 2012 Sep;51(9):746-53. doi: 10.1002/mc.20843. Epub 2011 Aug 30.
3 On the Role of Store-Operated Calcium Entry in Acute and Chronic Neurodegenerative Diseases.Front Mol Neurosci. 2018 Mar 22;11:87. doi: 10.3389/fnmol.2018.00087. eCollection 2018.
4 Calcium-sensing stromal interaction molecule 2 upregulates nuclear factor of activated T cells 1 and transforming growth factor- signaling to promote breast cancer metastasis.Breast Cancer Res. 2019 Aug 29;21(1):99. doi: 10.1186/s13058-019-1185-1.
5 STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses.Neurobiol Learn Mem. 2017 Feb;138:54-61. doi: 10.1016/j.nlm.2016.08.007. Epub 2016 Aug 18.
6 Stromal Interaction Molecule Deficiency in T Cells Promotes Spontaneous Follicular Helper T Cell Development and Causes Type 2 Immune Disorders.J Immunol. 2019 May 1;202(9):2616-2627. doi: 10.4049/jimmunol.1700610. Epub 2019 Mar 25.
7 STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia.Cell Rep. 2018 Sep 11;24(11):3045-3060.e5. doi: 10.1016/j.celrep.2018.08.030.
8 Enhanced expression of Stim, Orai, and TRPC transcripts and proteins in endothelial progenitor cells isolated from patients with primary myelofibrosis.PLoS One. 2014 Mar 6;9(3):e91099. doi: 10.1371/journal.pone.0091099. eCollection 2014.
9 STIM2 (Stromal Interaction Molecule 2)-Mediated Increase in Resting Cytosolic Free Ca(2+) Concentration Stimulates PASMC Proliferation in Pulmonary Arterial Hypertension.Hypertension. 2018 Mar;71(3):518-529. doi: 10.1161/HYPERTENSIONAHA.117.10503. Epub 2018 Jan 22.
10 Inverse regulation of melanoma growth and migration by Orai1/STIM2-dependent calcium entry.Pigment Cell Melanoma Res. 2014 May;27(3):442-53. doi: 10.1111/pcmr.12222. Epub 2014 Mar 7.
11 Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes.PLoS One. 2018 Dec 13;13(12):e0208981. doi: 10.1371/journal.pone.0208981. eCollection 2018.
12 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.
13 Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington's Disease.Front Cell Neurosci. 2018 Oct 26;12:381. doi: 10.3389/fncel.2018.00381. eCollection 2018.
14 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
15 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
16 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.
17 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
18 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.
19 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
20 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
21 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.
22 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
23 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
24 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.
25 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
26 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.