Names & Taxonomy
- Uniprot ID:
- O75460
- Entry Name:
- ERN1_HUMAN
- Status:
- reviewed
- Protein Names:
- Serine/threonine-protein kinase/endoribonuclease IRE1 (Endoplasmic reticulum-to-nucleus signaling 1) (Inositol-requiring protein 1) (hIRE1p) (Ire1-alpha) (IRE1a) [Includes: Serine/threonine-protein kinase (EC 2.7.11.1); Endoribonuclease (EC 3.1.26.-)]
- Gene Names:
- ERN1 IRE1
- Gene Names Primary:
- ERN1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 977
- Sequence:
- MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEPAFLPDPNDGSLYTLGSKNNEGLTKLPFTIPELVQASPCRSSDGILYMGKKQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYFDYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKVMHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMVHEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWLLIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSRDVEEKPAHAPARPEAPVDSMLKDMATIILSTFLLIGWVAFIITYPLSMHQQQQLQHQQFQKELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSGSSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKRILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAHLGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAVGRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQRQANILLGACSLDCLHPEKHEDVIARELIEKMIAMDPQKRPSAKHVLKHPFFWSLEKQLQFFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDLLRAMRNKKHHYRELPAEVRETLGSLPDDFVCYFTSRFPHLLAHTYRAMELCSHERLFQPYYFHEPPEPQPPVTPDAL
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Endoplasmic reticulum membrane
Function
- Function:
- Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Enzyme Regulation:
- ENZYME REGULATION: The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain.
- Active Site:
- ACT_SITE 688 688 Proton acceptor.
- Gene Ontology Go:
- AIP1-IRE1 complex
cytoplasm
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of endoplasmic reticulum membrane
Ire1 complex
IRE1-RACK1-PP2A complex
IRE1-TRAF2-ASK1 complex
mitochondrion
nuclear inner membrane
ADP binding
ATP binding
endoribonuclease activity
enzyme binding
Hsp70 protein binding
Hsp90 protein binding
identical protein binding
magnesium ion binding
protein homodimerization activity
protein serine/threonine kinase activity
activation of JUN kinase activity
activation of signaling protein activity involved in unfolded protein response
cell cycle arrest
cellular protein metabolic process
cellular response to glucose stimulus
cellular response to vascular endothelial growth factor stimulus
endoplasmic reticulum unfolded protein response
endothelial cell proliferation
insulin metabolic process
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
IRE1-mediated unfolded protein response
mRNA catabolic process
mRNA cleavage
mRNA endonucleolytic cleavage involved in unfolded protein response
mRNA splicing, via endonucleolytic cleavage and ligation
peptidyl-serine autophosphorylation
peptidyl-serine trans-autophosphorylation
positive regulation of endoplasmic reticulum unfolded protein response
positive regulation of RNA splicing
protein autophosphorylation
protein phosphorylation
regulation of macroautophagy
regulation of transcription, DNA-templated
response to endoplasmic reticulum stress
RNA phosphodiester bond hydrolysis, endonucleolytic
transcription, DNA-templated - Gene Ontology Biological Process:
- activation of JUN kinase activity
activation of signaling protein activity involved in unfolded protein response
cell cycle arrest
cellular protein metabolic process
cellular response to glucose stimulus
cellular response to vascular endothelial growth factor stimulus
endoplasmic reticulum unfolded protein response
endothelial cell proliferation
insulin metabolic process
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
IRE1-mediated unfolded protein response
mRNA catabolic process
mRNA cleavage
mRNA endonucleolytic cleavage involved in unfolded protein response
mRNA splicing, via endonucleolytic cleavage and ligation
peptidyl-serine autophosphorylation
peptidyl-serine trans-autophosphorylation
positive regulation of endoplasmic reticulum unfolded protein response
positive regulation of RNA splicing
protein autophosphorylation
protein phosphorylation
regulation of macroautophagy
regulation of transcription, DNA-templated
response to endoplasmic reticulum stress
RNA phosphodiester bond hydrolysis, endonucleolytic
transcription, DNA-templated - Gene Ontology Molecular Function:
- ADP binding
ATP binding
endoribonuclease activity
enzyme binding
Hsp70 protein binding
Hsp90 protein binding
identical protein binding
magnesium ion binding
protein homodimerization activity
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- AIP1-IRE1 complex
cytoplasm
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of endoplasmic reticulum membrane
Ire1 complex
IRE1-RACK1-PP2A complex
IRE1-TRAF2-ASK1 complex
mitochondrion
nuclear inner membrane - Keywords:
- 3D-structure
ADP-ribosylation
ATP-binding
Alternative splicing
Apoptosis
Complete proteome
Disulfide bond
Endoplasmic reticulum
Glycoprotein
Hydrolase
Kinase
Magnesium
Membrane
Metal-binding
Multifunctional enzyme
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Signal
Transcription
Transcription regulation
Transferase
Transmembrane
Transmembrane helix
Unfolded protein response - Interacts With:
- Itself; O08734; Q07812; Q07813; P20029; Q86TM6; Q9H2K8; Q12933; Q969M3