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endoplasmic reticulum to nucleus signaling 1

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Target not currently curated in GtoImmuPdb

Target id: 2020

Nomenclature: endoplasmic reticulum to nucleus signaling 1

Abbreviated Name: IRE1

Family: IRE family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 977 17q23.3 ERN1 endoplasmic reticulum to nucleus signaling 1
Mouse 1 977 11 E1 Ern1 endoplasmic reticulum to nucleus signalling 1
Rat - 965 10 q32.1 Ern1 endoplasmic reticulum to nucleus signaling 1
Previous and Unofficial Names Click here for help
inositol-requiring enzyme 1
Database Links Click here for help
Alphafold O75460 (Hs), Q9EQY0 (Mm)
BRENDA 2.7.11.1, 3.1.26.-
ChEMBL Target CHEMBL1163101 (Hs), CHEMBL4523450 (Mm)
Ensembl Gene ENSG00000178607 (Hs), ENSMUSG00000020715 (Mm), ENSRNOG00000012864 (Rn)
Entrez Gene 2081 (Hs), 78943 (Mm), 498013 (Rn)
Human Protein Atlas ENSG00000178607 (Hs)
KEGG Enzyme 2.7.11.1, 3.1.26.-
KEGG Gene hsa:2081 (Hs), mmu:78943 (Mm), rno:498013 (Rn)
OMIM 604033 (Hs)
Pharos O75460 (Hs)
RefSeq Nucleotide NM_001433 (Hs), NM_023913 (Mm), NM_001191926 (Rn)
RefSeq Protein NP_001424 (Hs), NP_076402 (Mm), NP_001178855 (Rn)
UniProtKB O75460 (Hs), Q9EQY0 (Mm)
Wikipedia ERN1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structure of human IRE1-alpha luminal domain
PDB Id:  2HZ6
Resolution:  3.1Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Human kinase and RNase domains in complex with ADP
PDB Id:  3P23
Ligand:  ADP   This ligand is endogenous
Resolution:  2.7Å
Species:  Human
References:  1
Enzyme Reaction Click here for help
EC Number: 2.7.11.1
EC Number: 3.1.26.-

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 34 [PMID: 24749861] Small molecule or natural product Hs Inhibition 7.3 pIC50 3
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [3]
Description: Inhibition of RNAse activity.
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,4
Key to terms and symbols Click column headers to sort
Target used in screen: ERN1
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
BMS-345541 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.6 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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1. Ali MM, Bagratuni T, Davenport EL, Nowak PR, Silva-Santisteban MC, Hardcastle A, McAndrews C, Rowlands MG, Morgan GJ, Aherne W et al.. (2011) Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J, 30 (5): 894-905. [PMID:21317875]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

3. Ranatunga S, Tang CH, Kang CW, Kriss CL, Kloppenburg BJ, Hu CC, Del Valle JR. (2014) Synthesis of novel tricyclic chromenone-based inhibitors of IRE-1 RNase activity. J Med Chem, 57 (10): 4289-301. [PMID:24749861]

4. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

5. Zhou J, Liu CY, Back SH, Clark RL, Peisach D, Xu Z, Kaufman RJ. (2006) The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response. Proc Natl Acad Sci USA, 103 (39): 14343-8. [PMID:16973740]

How to cite this page

IRE family: endoplasmic reticulum to nucleus signaling 1. Last modified on 09/02/2015. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2020.