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This gene encodes the transmembrane protein kinase inositol-requiring enzyme 1. The encoded protein contains two functional catalytic domains, a serine/threonine-protein kinase domain and an endoribonuclease domain. This protein functions as a sensor of unfolded proteins in the endoplasmic reticulum (ER) and triggers an intracellular signaling pathway termed the unfolded protein response (UPR). The UPR is an ER stress response that is conserved from yeast to mammals and activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones. This protein specifically mediates the splicing and activation of the stress response transcription factor X-box binding protein 1. [provided by RefSeq, Aug 2017]
ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) is a Protein Coding gene. Diseases associated with ERN1 include Arrhythmogenic Right Ventricular Dysplasia, Familial, 5 and Epiphyseal Dysplasia, Multiple, With Early-Onset Diabetes Mellitus. Among its related pathways are Spinocerebellar ataxia and Photodynamic therapy-induced unfolded protein response. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is ERN2.
Inositol-requiring enzyme 1 (IRE1) is a resident transmembrane ER protein with both kinase and endonuclease domains. Both yeast (IRE) and mammalian (IRE1alpha) homologs are involved in the degradation of misfolded proteins, as part of the unfolded protein response (UPR).
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0000287 | magnesium ion binding | IDA | 9637683 |
GO:0003824 | catalytic activity | IEA | -- |
GO:0004519 | endonuclease activity | IEA | -- |
GO:0004521 | endoribonuclease activity | IBA,IDA | 9637683 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005637 | nuclear inner membrane | IEA | -- |
GO:0005737 | cytoplasm | IDA | 19622636 |
GO:0005739 | mitochondrion | IEA | -- |
GO:0005783 | endoplasmic reticulum | IEA,IDA | 23529610 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Parkinson disease | ||
2 | Unfolded Protein Response (UPR) | ||
3 | Translational Control | ||
4 | Apoptosis Modulation and Signaling |
.31
|
|
5 | Autophagy - animal |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001935 | endothelial cell proliferation | IDA | 23529610 |
GO:0006379 | mRNA cleavage | ISS | -- |
GO:0006397 | mRNA processing | IEA | -- |
GO:0006402 | mRNA catabolic process | TAS | 22013210 |
GO:0006468 | protein phosphorylation | IDA | 9637683 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Magnesium | Approved, Experimental, Investigational | Pharma | 0 | |||
N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine | Experimental | Pharma | Target | 0 | ||
ATP | Investigational | Nutra | Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation | 0 | ||
APY29 | Pharma | IRE1α inhibitor, Inhibits IRE1alpha autophosphorylation; activates IRE1alpha endoribonuclease activity | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
4mu8C |
|
14003-96-4 |
|
|
Compound | Action | Cas Number |
---|---|---|
4mu8C | Inhibits IRE1alpha endoribonuclease activity | 14003-96-4 |
APY 29 | Inhibits IRE1alpha autophosphorylation; activates IRE1alpha endoribonuclease activity | 1216665-49-4 |
STF 083010 | Inhibits IRE1alpha endonuclease activity | 307543-71-1 |
Compound | Action | Cas Number |
---|---|---|
4μ8C | IRE1 Rnase inhibitor, potent and non-toxic | 14003-96-4 |
APY29 | IRE1α inhibitor | 1216665-49-4 |
STF 083010 | IRE1α endonuclease inhibitor | 307543-71-1 |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | ERN1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | ERN1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Ern1 30 17 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | ERN1 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Ern1 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | ERN1 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | ERN1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | ERN1 31 |
|
OneToOne | |
LOC417414 30 |
|
||||
Lizard (Anolis carolinensis) |
Reptilia | ERN1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | ern2 30 |
|
||
Str.12018 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | ern1 31 |
|
OneToOne | |
ern2 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Ire1 30 31 |
|
OneToMany | |
ire-1 32 |
|
|
|||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP004176 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | ire-1 30 31 |
|
OneToMany | |
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | IRE1 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.5230 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 17 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
711661 | Benign: not provided | 64,049,098(-) | G/A | SYNONYMOUS_VARIANT | |
711689 | Benign: not provided | 64,055,698(-) | G/C | MISSENSE_VARIANT | |
735286 | Likely Benign: not provided | 64,055,784(-) | C/T | SYNONYMOUS_VARIANT | |
740269 | Likely Benign: not provided | 64,072,063(-) | G/A | SYNONYMOUS_VARIANT | |
rs1279653488 | An ovarian serous carcinoma sample | p.Pro830Leu |
Disorder | Aliases | PubMed IDs |
---|---|---|
arrhythmogenic right ventricular dysplasia, familial, 5 |
|
|
epiphyseal dysplasia, multiple, with early-onset diabetes mellitus |
|
|
non-alcoholic fatty liver disease |
|
|
arrhythmogenic right ventricular dysplasia, familial, 9 |
|
|
alzheimer disease |
|
|