Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGQ2AOJ)

DOT Name Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3)
Synonyms IP3 receptor isoform 3; IP3R 3; InsP3R3; Type 3 inositol 1,4,5-trisphosphate receptor; Type 3 InsP3 receptor
Gene Name ITPR3
Related Disease
Charcot-Marie-Tooth disease, demyelinating, type 1J ( )
UniProt ID
ITPR3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6DQJ; 6DQN; 6DQS; 6DQV; 6DQZ; 6DR0; 6DR2; 6DRA; 6DRC; 6UQK; 7T3P; 7T3Q; 7T3R; 7T3T; 7T3U; 8TK8; 8TKD; 8TKE; 8TKF; 8TKG; 8TKH; 8TKI; 8TL9; 8TLA
Pfam ID
PF08709 ; PF00520 ; PF02815 ; PF08454 ; PF01365
Sequence
MSEMSSFLHIGDIVSLYAEGSVNGFISTLGLVDDRCVVEPAAGDLDNPPKKFRDCLFKVC
PMNRYSAQKQYWKAKQTKQDKEKIADVVLLQKLQHAAQMEQKQNDTENKKVHGDVVKYGS
VIQLLHMKSNKYLTVNKRLPALLEKNAMRVTLDATGNEGSWLFIQPFWKLRSNGDNVVVG
DKVILNPVNAGQPLHASNYELSDNAGCKEVNSVNCNTSWKINLFMQFRDHLEEVLKGGDV
VRLFHAEQEKFLTCDEYKGKLQVFLRTTLRQSATSATSSNALWEVEVVHHDPCRGGAGHW
NGLYRFKHLATGNYLAAEENPSYKGDASDPKAAGMGAQGRTGRRNAGEKIKYCLVAVPHG
NDIASLFELDPTTLQKTDSFVPRNSYVRLRHLCTNTWIQSTNVPIDIEEERPIRLMLGTC
PTKEDKEAFAIVSVPVSEIRDLDFANDASSMLASAVEKLNEGFISQNDRRFVIQLLEDLV
FFVSDVPNNGQNVLDIMVTKPNRERQKLMREQNILKQVFGILKAPFREKGGEGPLVRLEE
LSDQKNAPYQHMFRLCYRVLRHSQEDYRKNQEHIAKQFGMMQSQIGYDILAEDTITALLH
NNRKLLEKHITKTEVETFVSLVRKNREPRFLDYLSDLCVSNHIAIPVTQELICKCVLDPK
NSDILIRTELRPVKEMAQSHEYLSIEYSEEEVWLTWTDKNNEHHEKSVRQLAQEARAGNA
HDENVLSYYRYQLKLFARMCLDRQYLAIDEISQQLGVDLIFLCMADEMLPFDLRASFCHL
MLHVHVDRDPQELVTPVKFARLWTEIPTAITIKDYDSNLNASRDDKKNKFANTMEFVEDY
LNNVVSEAVPFANEEKNKLTFEVVSLAHNLIYFGFYSFSELLRLTRTLLGIIDCVQGPPA
MLQAYEDPGGKNVRRSIQGVGHMMSTMVLSRKQSVFSAPSLSAGASAAEPLDRSKFEENE
DIVVMETKLKILEILQFILNVRLDYRISYLLSVFKKEFVEVFPMQDSGADGTAPAFDSTT
ANMNLDRIGEQAEAMFGVGKTSSMLEVDDEGGRMFLRVLIHLTMHDYAPLVSGALQLLFK
HFSQRQEAMHTFKQVQLLISAQDVENYKVIKSELDRLRTMVEKSELWVDKKGSGKGEEVE
AGAAKDKKERPTDEEGFLHPPGEKSSENYQIVKGILERLNKMCGVGEQMRKKQQRLLKNM
DAHKVMLDLLQIPYDKGDAKMMEILRYTHQFLQKFCAGNPGNQALLHKHLHLFLTPGLLE
AETMQHIFLNNYQLCSEISEPVLQHFVHLLATHGRHVQYLDFLHTVIKAEGKYVKKCQDM
IMTELTNAGDDVVVFYNDKASLAHLLDMMKAARDGVEDHSPLMYHISLVDLLAACAEGKN
VYTEIKCTSLLPLEDVVSVVTHEDCITEVKMAYVNFVNHCYVDTEVEMKEIYTSNHIWTL
FENFTLDMARVCSKREKRVADPTLEKYVLSVVLDTINAFFSSPFSENSTSLQTHQTIVVQ
LLQSTTRLLECPWLQQQHKGSVEACIRTLAMVAKGRAILLPMDLDAHISSMLSSGASCAA
AAQRNASSYKATTRAFPRVTPTANQWDYKNIIEKLQDIITALEERLKPLVQAELSVLVDV
LHWPELLFLEGSEAYQRCESGGFLSKLIQHTKDLMESEEKLCIKVLRTLQQMLLKKTKYG
DRGNQLRKMLLQNYLQNRKSTSRGDLPDPIGTGLDPDWSAIAATQCRLDKEGATKLVCDL
ITSTKNEKIFQESIGLAIHLLDGGNTEIQKSFHNLMMSDKKSERFFKVLHDRMKRAQQET
KSTVAVNMNDLGSQPHEDREPVDPTTKGRVASFSIPGSSSRYSLGPSLRRGHEVSERVQS
SEMGTSVLIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCETLQFLDIMCGSTTG
GLGLLGLYINEDNVGLVIQTLETLTEYCQGPCHENQTCIVTHESNGIDIITALILNDISP
LCKYRMDLVLQLKDNASKLLLALMESRHDSENAERILISLRPQELVDVIKKAYLQEEERE
NSEVSPREVGHNIYILALQLSRHNKQLQHLLKPVKRIQEEEAEGISSMLSLNNKQLSQML
KSSAPAQEEEEDPLAYYENHTSQIEIVRQDRSMEQIVFPVPGICQFLTEETKHRLFTTTE
QDEQGSKVSDFFDQSSFLHNEMEWQRKLRSMPLIYWFSRRMTLWGSISFNLAVFINIIIA
FFYPYMEGASTGVLDSPLISLLFWILICFSIAALFTKRYSIRPLIVALILRSIYYLGIGP
TLNILGALNLTNKIVFVVSFVGNRGTFIRGYKAMVMDMEFLYHVGYILTSVLGLFAHELF
YSILLFDLIYREETLFNVIKSVTRNGRSILLTALLALILVYLFSIVGFLFLKDDFILEVD
RLPNNHSTASPLGMPHGAAAFVDTCSGDKMDCVSGLSVPEVLEEDRELDSTERACDTLLM
CIVTVMNHGLRNGGGVGDILRKPSKDESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTF
ADLRSEKQKKEEILKTTCFICGLERDKFDNKTVSFEEHIKLEHNMWNYLYFIVLVRVKNK
TDYTGPESYVAQMIKNKNLDWFPRMRAMSLVSNEGEGEQNEIRILQDKLNSTMKLVSHLT
AQLNELKEQMTEQRKRRQRLGFVDVQNCISR
Function Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. Involved in cellular calcium ion homeostasis.
Tissue Specificity Expressed in intestinal crypt and villus epithelial cells.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
cGMP-PKG sig.ling pathway (hsa04022 )
Phosphatidylinositol sig.ling system (hsa04070 )
Oocyte meiosis (hsa04114 )
Apoptosis (hsa04210 )
Cellular senescence (hsa04218 )
Vascular smooth muscle contraction (hsa04270 )
Apelin sig.ling pathway (hsa04371 )
Osteoclast differentiation (hsa04380 )
Gap junction (hsa04540 )
Platelet activation (hsa04611 )
NOD-like receptor sig.ling pathway (hsa04621 )
C-type lectin receptor sig.ling pathway (hsa04625 )
Circadian entrainment (hsa04713 )
Long-term potentiation (hsa04720 )
Retrograde endocan.binoid sig.ling (hsa04723 )
Glutamatergic sy.pse (hsa04724 )
Cholinergic sy.pse (hsa04725 )
Serotonergic sy.pse (hsa04726 )
Dopaminergic sy.pse (hsa04728 )
Long-term depression (hsa04730 )
Taste transduction (hsa04742 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
Insulin secretion (hsa04911 )
GnRH sig.ling pathway (hsa04912 )
Estrogen sig.ling pathway (hsa04915 )
Thyroid hormone synthesis (hsa04918 )
Oxytocin sig.ling pathway (hsa04921 )
Glucagon sig.ling pathway (hsa04922 )
Renin secretion (hsa04924 )
Aldosterone synthesis and secretion (hsa04925 )
Cortisol synthesis and secretion (hsa04927 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
GnRH secretion (hsa04929 )
Cushing syndrome (hsa04934 )
Growth hormone synthesis, secretion and action (hsa04935 )
Salivary secretion (hsa04970 )
Gastric acid secretion (hsa04971 )
Pancreatic secretion (hsa04972 )
Alzheimer disease (hsa05010 )
Parkinson disease (hsa05012 )
Amyotrophic lateral sclerosis (hsa05014 )
Spinocerebellar ataxia (hsa05017 )
Prion disease (hsa05020 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Shigellosis (hsa05131 )
Human cytomegalovirus infection (hsa05163 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Human immunodeficiency virus 1 infection (hsa05170 )
Proteoglycans in cancer (hsa05205 )
Reactome Pathway
Effects of PIP2 hydrolysis (R-HSA-114508 )
Elevation of cytosolic Ca2+ levels (R-HSA-139853 )
DAG and IP3 signaling (R-HSA-1489509 )
Role of phospholipids in phagocytosis (R-HSA-2029485 )
FCERI mediated Ca+2 mobilization (R-HSA-2871809 )
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676 )
Ca2+ pathway (R-HSA-4086398 )
Regulation of insulin secretion (R-HSA-422356 )
VEGFR2 mediated cell proliferation (R-HSA-5218921 )
Ion homeostasis (R-HSA-5578775 )
CLEC7A (Dectin-1) induces NFAT activation (R-HSA-5607763 )
FCGR3A-mediated IL10 synthesis (R-HSA-9664323 )
Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207 )
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695 )
PLC beta mediated events (R-HSA-112043 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Charcot-Marie-Tooth disease, demyelinating, type 1J DIS5XDH2 Limited Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
23 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 Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [7]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [9]
Quercetin DM3NC4M Approved Quercetin increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [10]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [11]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [12]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [13]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [8]
Menadione DMSJDTY Approved Menadione affects the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [12]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [14]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [16]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [17]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [18]
AMEP DMFELMQ Phase 1 AMEP decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [19]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [23]
Glyphosate DM0AFY7 Investigative Glyphosate affects the expression of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [19]
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⏷ Show the Full List of 23 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Resveratrol DM3RWXL Phase 3 Resveratrol increases the phosphorylation of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [22]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3). [20]
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References

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5 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
6 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.
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8 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.
9 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.
10 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.
11 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.
12 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
13 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
14 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.
15 Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling. J Proteome Res. 2014 Dec 5;13(12):5734-42. doi: 10.1021/pr500714a. Epub 2014 Oct 29.
16 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
17 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.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
19 Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
20 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.
21 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
22 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
23 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.