ERN1

ERN1 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.

ERN1 Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>ERN1

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>ERN1

ERN1 Alternative Names

ERN1, FLJ30999, IRE1, IRE1P, IRE1a, MGC163277, MGC163279, hIRE1p [Homo sapiens]

Ern1, RP23-418O11.11-001, 9030414B18Rik, AI225830, C85377, Ire1a, Ire1alpha, Ire1p [Mus musculus]

Summaries for ERN1

Entrez Gene summary for ERN1:

The protein encoded by this ERN1 gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1 gene product. ERN1 protein possesses intrinsic kinase activity and an endoribonuclease activity and it is important in altering gene expression as a response to endoplasmic reticulum-based stress signals. [provided by RefSeq, Jul 2008]

Wikipedia summary for ERN1:

Serine/threonine-protein kinase/endoribonuclease IRE1 is an enzyme that in humans is encoded by the ERN1 gene.
The protein encoded by this ERN1 gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1 gene product. ERN1 possesses intrinsic kinase activity and an endoribonuclease activity and it is important in altering gene expression as a response to endoplasmic reticulum-based stress signals (mainly the unfolded protein response). Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Human ERN1 Protein General Information

 

• Protein names: Serine/threonine-protein kinase/endoribonuclease IRE1
• Sequence length: 977 AA.
• Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
• Cofactor: Magnesium.
• Enzyme regulation: The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain.
• Sequence similarities: ERN1 belongs to the protein kinase superfamily. Ser/Thr protein kinase family. ERN1 contains 1 KEN domain. ERN1 contains 1 protein kinase domain.
• Post-translational modification: Autophosphorylated.
• Subunit structure: 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.
• Subcellular location: Endoplasmic reticulum membrane; Single-pass type I membrane protein
• Tissue specificity: ERN1 is ubiquitously expressed. High levels observed in pancreatic tissue.

General information above from UniProt

Function for ERN1 Protein

UniProtKB:

ERN1 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.

Genatlas:

• ERN1 is involved in electron transport, protein amino acid phosphorylation
• ERN1 has an intrinsic kinase activity and an endoribonuclease activity
• ERN1 has a unique function of relieving ER stress in cells
• ERN1 induces unconventional splicing of mRNA coding a specific transcription factor for activating the unfolded protein response
• activating chaperone genes in response to stress in the ER and also activating JNK
• ERN1 promotes cell survival by reducing misfolded protein levels
• ERN1 is type I transmembrane Ser/Thr kinase that also has site-specific endoribonuclease (RNase) activity
• induction of ER quality control proteins is mediated by ERN1 which activates the transcription factor XBP1 via an unconventional splicing event
• ERN1 oligomerizes in the ER membrane and oligomerization correlates with the onset of ERN1 phosphorylation and RNase activity
• ERN1's activity is governed by a timer that may be important in switching the UPR (unfolded protein response) from the initially cytoprotective phase to the apoptotic mode
• ERN1 splices the precursor unspliced form of X-box–binding protein 1 messenger RNA (XBP1u mRNA) on the ER membrane to yield an active transcription factor (XBP1s), leading to the alleviation of the stress

Homology for human ERN1

• homolog to murine Ern1 (93.3pc)
• homolog to rattus Ern1 (93.8pc)