Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUS6GKR)

DOT Name Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2)
Synonyms Endoplasmic reticulum-to-nucleus signaling 2; Inositol-requiring protein 2; hIRE2p; Ire1-beta; IRE1b
Gene Name ERN2
Related Disease
Hepatocellular carcinoma ( )
Colorectal carcinoma ( )
Cystic fibrosis ( )
Neoplasm ( )
Fetal growth restriction ( )
UniProt ID
ERN2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.1; 3.1.26.-
Pfam ID
PF00069 ; PF06479
Sequence
MASAVRGSRPWPRLGLQLQFAALLLGTLSPQVHTLRPENLLLVSTLDGSLHALSKQTGDL
KWTLRDDPVIEGPMYVTEMAFLSDPADGSLYILGTQKQQGLMKLPFTIPELVHASPCRSS
DGVFYTGRKQDAWFVVDPESGETQMTLTTEGPSTPRLYIGRTQYTVTMHDPRAPALRWNT
TYRRYSAPPMDGSPGKYMSHLASCGMGLLLTVDPGSGTVLWTQDLGVPVMGVYTWHQDGL
RQLPHLTLARDTLHFLALRWGHIRLPASGPRDTATLFSTLDTQLLMTLYVGKDETGFYVS
KALVHTGVALVPRGLTLAPADGPTTDEVTLQVSGEREGSPSTAVRYPSGSVALPSQWLLI
GHHELPPVLHTTMLRVHPTLGSGTAETRPPENTQAPAFFLELLSLSREKLWDSELHPEEK
TPDSYLGLGPQDLLAASLTAVLLGGWILFVMRQQQPQVVEKQQETPLAPADFAHISQDAQ
SLHSGASRRSQKRLQSPSKQAQPLDDPEAEQLTVVGKISFNPKDVLGRGAGGTFVFRGQF
EGRAVAVKRLLRECFGLVRREVQLLQESDRHPNVLRYFCTERGPQFHYIALELCRASLQE
YVENPDLDRGGLEPEVVLQQLMSGLAHLHSLHIVHRDLKPGNILITGPDSQGLGRVVLSD
FGLCKKLPAGRCSFSLHSGIPGTEGWMAPELLQLLPPDSPTSAVDIFSAGCVFYYVLSGG
SHPFGDSLYRQANILTGAPCLAHLEEEVHDKVVARDLVGAMLSPLPQPRPSAPQVLAHPF
FWSRAKQLQFFQDVSDWLEKESEQEPLVRALEAGGCAVVRDNWHEHISMPLQTDLRKFRS
YKGTSVRDLLRAVRNKKHHYRELPVEVRQALGQVPDGFVQYFTNRFPRLLLHTHRAMRSC
ASESLFLPYYPPDSEARRPCPGATGR
Function Induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. Pro-apoptotic. Appears to play no role in the unfolded-protein response, unlike closely related proteins.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Definitive Genetic Variation [1]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [2]
Cystic fibrosis DIS2OK1Q Strong Biomarker [3]
Neoplasm DISZKGEW Strong Altered Expression [4]
Fetal growth restriction DIS5WEJ5 Limited Altered Expression [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2). [9]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin increases the expression of Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2). [7]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2). [8]
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References

1 Therapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma.J Vasc Interv Radiol. 2019 Jul;30(7):1098-1105. doi: 10.1016/j.jvir.2019.02.023. Epub 2019 May 14.
2 Expression of inositol-requiring enzyme 1 is downregulated in colorectal cancer.Oncol Lett. 2017 Mar;13(3):1109-1118. doi: 10.3892/ol.2017.5590. Epub 2017 Jan 11.
3 IL-1 dominates the promucin secretory cytokine profile in cystic fibrosis.J Clin Invest. 2019 Oct 1;129(10):4433-4450. doi: 10.1172/JCI125669.
4 Expression of inositol-requiring enzyme 1 is downregulated in azoxymethane/dextran sulfate sodium-induced mouse colonic tumors.Exp Ther Med. 2019 Apr;17(4):3181-3188. doi: 10.3892/etm.2019.7317. Epub 2019 Feb 26.
5 Maternal Protein Restriction Induces Alterations in Hepatic Unfolded Protein Response-Related Molecules in Adult Rat Offspring.Front Endocrinol (Lausanne). 2018 Nov 20;9:676. doi: 10.3389/fendo.2018.00676. eCollection 2018.
6 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.
7 Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
8 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
9 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.