BioPAX pathway converted from "IRE1alpha activates chaperones" in the Reactome database. IRE1alpha activates chaperones IRE1alpha activates chaperones This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> IRE1 binds IRE1 forming dimer IRE1 binds IRE1 forming dimer This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10718207 2 endoplasmic reticulum membrane GO 0005789 UniProt:Q09499 ire-1 Reactome http://www.reactome.org Caenorhabditis elegans NCBI Taxonomy 6239 UniProt Q09499 Chain Coordinates 19 EQUAL 977 EQUAL Reactome DB_ID: 10718209 1 IRE1 dimer [endoplasmic reticulum membrane] IRE1 dimer Reactome DB_ID: 10718207 2 19 EQUAL 977 EQUAL Reactome Database ID Release 81 10718209 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10718209 Reactome R-CEL-381200 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-381200.1 Reactome Database ID Release 81 10718219 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10718219 Reactome R-CEL-381109 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-381109.1 The dissociation of the IRE1-alpha:BiP heterodimer liberates IRE1-alpha, which forms homodimers. Dimer formation is initiated by interaction between the N-terminal, luminal domains. 10835430 Pubmed 2000 Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum Liu, CY Schröder, Martin Kaufman, RJ J Biol Chem 275:24881-5 16973740 Pubmed 2006 The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response Zhou, J Liu, CY Back, SH Clark, RL Peisach, D Xu, Z Kaufman, RJ Proc Natl Acad Sci U S A 103:14343-8 18191223 Pubmed 2008 Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing Lee, KP Dey, M Neculai, D Cao, C Dever, TE Sicheri, F Cell 132:89-100 11897784 Pubmed 2002 The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain Liu, CY Wong, HN Schauerte, JA Kaufman, RJ J Biol Chem 277:18346-56 11069889 Pubmed 2000 The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response Tirasophon, W Lee, K Callaghan, B Welihinda, A Kaufman, RJ Genes Dev 14:2725-36 16365312 Pubmed 2005 On the mechanism of sensing unfolded protein in the endoplasmic reticulum Credle, JJ Finer-Moore, JS Papa, FR Stroud, RM Walter, P Proc Natl Acad Sci U S A 102:18773-84 inferred by electronic annotation IEA GO IEA 2.7.11.1 IRE1 dimer autophosphorylates IRE1 dimer autophosphorylates This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10718209 1 Reactome DB_ID: 113592 2 cytosol GO 0005829 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 29370 2 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 Reactome DB_ID: 10718214 1 p-S724-IRE1 dimer [endoplasmic reticulum membrane] p-S724-IRE1 dimer Reactome DB_ID: 10718212 2 O-phospho-L-serine at 724 (in Homo sapiens) 724 EQUAL O-phospho-L-serine [MOD:00046] 19 EQUAL 977 EQUAL Reactome Database ID Release 81 10718214 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10718214 Reactome R-CEL-381154 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-381154.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10718209 GO 0004674 GO molecular function Reactome Database ID Release 81 10718215 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10718215 Reactome Database ID Release 81 10718217 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10718217 Reactome R-CEL-381091 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-381091.1 Dimerization of the N-terminal luminal regions of IRE1-alpha brings the cytosolic C-terminal regions in proximity. The C-terminal region possesses kinase activity and the homodimer trans-autophosphorylates. From homology with Saccharomyces IRE1-alpha the phosphorylation of human IRE1-alpha is believed to be at Ser724. 9637683 Pubmed 1998 A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells Tirasophon, W Welihinda, AA Kaufman, RJ Genes Dev 12:1812-24 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 81 10772650 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10772650 Reactome R-CEL-381070 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-381070.1 GO 0036498 GO biological process IRE1-alpha is a single-pass transmembrane protein that resides in the endoplasmic reticulum (ER) membrane. The C-terminus of IRE1-alpha is located in the cytosol; the N-terminus is located in the ER lumen. In unstressed cells IRE1-alpha exists in an inactive heterodimeric complex with BiP such that BiP in the ER lumen binds the N-terminal region of IRE1-alpha. Upon accumulation of unfolded proteins in the ER, BiP binds the unfolded protein and the IRE1-alpha:BiP complex dissociates. The dissociated IRE1-alpha then forms homodimers. Initially the luminal N-terminal regions pair. This is followed by trans-autophosphorylation of IRE1-alpha at Ser724 in the cytosolic C-terminal region. The phosphorylation causes a conformational change that allows the dimer to bind ADP, causing a further conformational change to yield back-to-back pairing of the cytosolic C-terminal regions of IRE1-alpha. The fully paired IRE1-alpha homodimer has endoribonuclease activity and cleaves the mRNA encoding Xbp-1. A 26 residue polyribonucleotide is released and the 5' and 3' fragments of the original Xbp-1 mRNA are rejoined. The spliced Xbp-1 message encodes Xbp-1 (S), a potent activator of transcription. Xbp-1 (S) together with the ubiquitous transcription factor NF-Y bind the ER Stress Responsive Element (ERSE) in a number of genes encoding chaperones. Recent data suggest that the IRE1-alpha homodimer can also cleave specific subsets of mRNAs, including the insulin (INS) mRNA in pancreatic beta cells. 18436705 Pubmed 2008 The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes Scheuner, D Kaufman, RJ Endocr Rev 29:317-33 18048764 Pubmed 2008 The role for endoplasmic reticulum stress in diabetes mellitus Eizirik, DL Cardozo, AK Cnop, M Endocr Rev 29:42-61 18038217 Pubmed 2008 Endoplasmic reticulum stress responses Schröder, Martin Cell Mol Life Sci 65:862-94 inferred by electronic annotation IEA GO IEA