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MGP000987

UniProt Annotations

Entry Information
Gene Nameendoplasmic reticulum to nucleus signaling 1
Protein EntryERN1_HUMAN
UniProt IDO75460
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=O75460-1; Sequence=Displayed; Name=2; IsoId=O75460-2; Sequence=VSP_034582, VSP_034583;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein. {ECO:0000269|PubMed:9637683}.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme RegulationThe kinase domain is activated by trans- autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain. {ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:9637683}.
FunctionSenses 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. {ECO:0000250|UniProtKB:Q9EQY0, ECO:0000269|PubMed:11175748, ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:9637683}.
InteractionSelf; NbExp=2; IntAct=EBI-371750, EBI-371750; O08734:Bak1 (xeno); NbExp=2; IntAct=EBI-371750, EBI-822441; Q07812:BAX; NbExp=2; IntAct=EBI-371750, EBI-516580; Q07813:Bax (xeno); NbExp=2; IntAct=EBI-371750, EBI-700711; P20029:Hspa5 (xeno); NbExp=2; IntAct=EBI-371750, EBI-772325; Q86TM6:SYVN1; NbExp=2; IntAct=EBI-371750, EBI-947849; Q9H2K8:TAOK3; NbExp=3; IntAct=EBI-371750, EBI-1384100; Q12933:TRAF2; NbExp=3; IntAct=EBI-371750, EBI-355744;
PtmADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities.
PtmAutophosphorylated. {ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:9637683}.
SimilarityBelongs to the protein kinase superfamily. Ser/Thr protein kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 1 KEN domain. {ECO:0000255|PROSITE- ProRule:PRU00725}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationEndoplasmic reticulum membrane {ECO:0000269|PubMed:9637683}; Single-pass type I membrane protein {ECO:0000269|PubMed:9637683}.
SubunitInteracts with DAB2IP (via PH domain); the interaction occurs in a ER stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1 (By similarity). Homodimer; disulfide-linked. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Also binds HSPA5, a negative regulator of the unfolded protein response. This interaction may disrupt homodimerization and prevent activation of ERN1. Interacts with TAOK3 and TRAF2. {ECO:0000250, ECO:0000269|PubMed:11278723, ECO:0000269|PubMed:12637535}.
Tissue SpecificityUbiquitously expressed. High levels observed in pancreatic tissue. {ECO:0000269|PubMed:9637683}.
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