Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY9R6FZ)

DOT Name Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)
Synonyms Endoplasmic reticulum-to-nucleus signaling 1; Inositol-requiring protein 1; hIRE1p; Ire1-alpha; IRE1a
Gene Name ERN1
UniProt ID
ERN1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2HZ6; 3P23; 4U6R; 4YZ9; 4YZC; 4YZD; 4Z7G; 4Z7H; 5HGI; 6HV0; 6HX1; 6SHC; 6URC; 6W39; 6W3A; 6W3B; 6W3C; 6W3E; 6W3K; 6XDB; 6XDD; 6XDF; 7BMK
EC Number
2.7.11.1; 3.1.26.-
Pfam ID
PF00069 ; PF06479
Sequence
MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDP
VLQVPTHVEEPAFLPDPNDGSLYTLGSKNNEGLTKLPFTIPELVQASPCRSSDGILYMGK
KQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYF
DYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKV
MHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMV
HEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWL
LIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSR
DVEEKPAHAPARPEAPVDSMLKDMATIILSTFLLIGWVAFIITYPLSMHQQQQLQHQQFQ
KELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSG
SSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKR
ILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAH
LGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAV
GRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQ
RQANILLGACSLDCLHPEKHEDVIARELIEKMIAMDPQKRPSAKHVLKHPFFWSLEKQLQ
FFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDL
LRAMRNKKHHYRELPAEVRETLGSLPDDFVCYFTSRFPHLLAHTYRAMELCSHERLFQPY
YFHEPPEPQPPVTPDAL
Function
Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. Accumulation of misfolded proteins in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity. The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA. The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes. Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A.
Tissue Specificity Ubiquitously expressed. High levels observed in pancreatic tissue.
KEGG Pathway
Autophagy - animal (hsa04140 )
Protein processing in endoplasmic reticulum (hsa04141 )
Apoptosis (hsa04210 )
Non-alcoholic fatty liver disease (hsa04932 )
Alzheimer disease (hsa05010 )
Parkinson disease (hsa05012 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Spinocerebellar ataxia (hsa05017 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Lipid and atherosclerosis (hsa05417 )
Reactome Pathway
IRE1alpha activates chaperones (R-HSA-381070 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Bortezomib DMNO38U Approved Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) decreases the response to substance of Bortezomib. [53]
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9 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 Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [1]
Quercetin DM3NC4M Approved Quercetin increases the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [8]
Cannabidiol DM0659E Approved Cannabidiol increases the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [14]
Methamphetamine DMPM4SK Approved Methamphetamine increases the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [19]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [30]
Rocilinostat DMSTH01 Phase 2 Rocilinostat affects the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [35]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [47]
D-glucose DMMG2TO Investigative D-glucose increases the phosphorylation of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [48]
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⏷ Show the Full List of 9 Drug(s)
53 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [11]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [12]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [13]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [13]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [15]
Ethanol DMDRQZU Approved Ethanol increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [16]
Paclitaxel DMLB81S Approved Paclitaxel increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [17]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [11]
Indomethacin DMSC4A7 Approved Indomethacin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [13]
Rifampicin DM5DSFZ Approved Rifampicin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [13]
Sulindac DM2QHZU Approved Sulindac increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [13]
Capsaicin DMGMF6V Approved Capsaicin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [18]
Sodium phenylbutyrate DMXLBCQ Approved Sodium phenylbutyrate decreases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [20]
Sertraline DM0FB1J Approved Sertraline increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [21]
Glucosamine DM4ZLFD Approved Glucosamine increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [22]
Cantharidin DMBP5N3 Approved Cantharidin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [23]
Allopurinol DMLPAOB Approved Allopurinol increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [13]
Hydroxychloroquine DMSIVND Approved Hydroxychloroquine increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [24]
Pyrazinamide DM4IF32 Approved Pyrazinamide increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [25]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [26]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [27]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [28]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [29]
Thymoquinone DMVDTR2 Phase 2/3 Thymoquinone increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [31]
URSOLIC ACID DM4SOAW Phase 2 URSOLIC ACID increases the activity of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [32]
ME-344 DM6JN19 Phase 1/2 ME-344 increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [34]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [36]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [37]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [9]
MG-132 DMKA2YS Preclinical MG-132 increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [38]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [39]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [40]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [41]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [42]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [43]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [44]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [45]
Glyphosate DM0AFY7 Investigative Glyphosate increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [46]
Butanoic acid DMTAJP7 Investigative Butanoic acid increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [49]
Okadaic acid DM47CO1 Investigative Okadaic acid increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [50]
NORCANTHARIDIN DM9B6Y1 Investigative NORCANTHARIDIN increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [17]
1,4-Dithiothreitol DMIFOXE Investigative 1,4-Dithiothreitol increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [24]
NMS-873 DMYKZ6U Investigative NMS-873 increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [51]
TINGENIN B DMEV7FY Investigative TINGENIN B increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1). [52]
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⏷ Show the Full List of 53 Drug(s)

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