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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

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 (ER) 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
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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.-

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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 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. U.S.A., 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 02/12/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2020.