Ire1 protein; serine/threonine protein kinase/endoribonuclease IRE1; inositol-requiring 1; hIRE1p; IRE1a; Ire1-alpha; endoplasmic reticulum-to-nucleus signaling 1 (IRE1, ERN1)

Function

• a sensor for the accumulation of unfolded proteins in the endoplasmic reticulum (ER)
• Ire1 initiates the unfolded protein response pathway, triggering growth arrest & apoptosis
• senses unfolded proteins in the lumen of the ER 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 & triggering growth arrest & apoptosis
• Ire1 may be a substrate of aspartyl protease activity of presenilins
• binds HSPA5, a negative regulator of the unfolded protein response; bindin may disrupt homodimerization & prevent activation of ERN1
• autophosphorylated

Structure

• homodimer; disulfide-linked
• dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains & stabilized by disulfide bridges.
• belongs to the protein kinase superfamily, Ser/Thr protein kinase family
• contains 1 KEN domain
• contains 1 protein kinase domain; kinase domain is activated by trans-autophosphorylation kinase activity is required for activation of the endoribonuclease domain

Cofactor: Mg+2

Compartment

endoplasmic reticulum membrane

Alternative splicing

named isoforms=2

Expression

• ubiquitously expressed
• high levels observed in pancreatic tissue

More general terms

• membrane protein
• glycoprotein
• serine/threonine kinase
• endoribonuclease

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2081
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2081
• OMIM: https://mirror.omim.org/entry/604033
• UniProt: http://www.uniprot.org/uniprot/O75460.html