Summary

Name ERN1
Full Name Serine/threonine-protein kinase/endoribonuclease IRE1
Synonyms Endoplasmic reticulum-to-nucleus signaling 1, Inositol-requiring protein 1, hIRE1p, Ire1-alpha, IRE1a | IRE1
Primary ID O75460
Links - -
Type protein
Relations 13
Pathways COVID-19 Causal Network, SARS-CoV ER STRESS
Function Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11779464, PubMed:11175748, PubMed:12637535, PubMed:9637683, PubMed:21317875, PubMed:28128204). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP (PubMed:21317875). 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 (PubMed:21317875). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11779464, PubMed:24508390, PubMed:21317875). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:24508390, PubMed:21317875). 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 (PubMed:21884936, PubMed:28067262).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation ERN1 0.2
Publications: 1 Organism: In Vitro
Pathways:COVID-19 Causal Network, SARS-CoV ER STRESS
+ up-regulates img/indirect-activation.png ERN1 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ER STRESS
+ up-regulates img/indirect-activation.png ERN1 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network
+ up-regulates activity img/direct-activation.png binding TRAF2 0.668
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/indirect_inhibition.png ERN1 0.2
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:COVID-19 Causal Network, SARS-CoV ER STRESS
+ up-regulates activity img/direct-activation.png binding ERN1 0.375
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png JUN 0.39
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ERN1 0.32
Publications: 1 Organism: Mus Musculus
+ up-regulates quantity by expression img/direct-activation.png post transcriptional regulation XBP1 (isoform 2) 0.631
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ER STRESS
+ down-regulates activity img/direct_inhibition.png binding ERN1 0.812
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ER STRESS
+ down-regulates activity img/indirect_inhibition.png JNK 0.32
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ER STRESS
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation OS9 0.436
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ERN1 0.319
Publications: 1 Organism: Mus Musculus