BioPAX pathway converted from "IRE1alpha activates chaperones" in the Reactome database.
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>
LEFT-TO-RIGHT
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>
ERN1
ire-1
Q09499
Reactome DB_ID: 10718207
endoplasmic reticulum membrane
GENE ONTOLOGY
GO:0005789
UniProt:Q09499
ire-1
Caenorhabditis elegans
NCBI Taxonomy
6239
UniProt
Q09499
19
EQUAL
977
EQUAL
Reactome Database ID Release 81
10718207
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=10718207
Reactome
R-CEL-381076
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-381076.1
Reactome
http://www.reactome.org
2
IRE1 dimer
Reactome DB_ID: 10718209
2
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.
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
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
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
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
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 from electronic annotation
EVIDENCE CODE
ECO:0000203
LEFT-TO-RIGHT
2.7.11.1
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>
ATP
Adenosine 5'-triphosphate
ATP(4-)
Reactome DB_ID: 113592
cytosol
GENE ONTOLOGY
GO:0005829
ATP(4-) [ChEBI:30616]
ATP(4-)
ATP
atp
Adenosine 5'-triphosphate
ChEBI
CHEBI:30616
Reactome Database ID Release 81
113592
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=113592
Reactome
R-ALL-113592
5
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-ALL-113592.5
COMPOUND
C00002
additional information
MI
MI:0361
2
ADP
Adenosine 5'-diphosphate
ADP(3-)
Reactome DB_ID: 29370
ADP(3-) [ChEBI:456216]
ADP(3-)
ADP
5'-O-[(phosphonatooxy)phosphinato]adenosine
ADP trianion
ChEBI
CHEBI:456216
Reactome Database ID Release 81
29370
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=29370
Reactome
R-ALL-29370
5
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-ALL-29370.5
COMPOUND
C00008
2
p-S724-IRE1 dimer
Reactome DB_ID: 10718214
Q09499
phospho-ire-1
p-S724-ERN1
Reactome DB_ID: 10718212
724
EQUAL
O-phospho-L-serine
MOD
MOD:00046
19
EQUAL
977
EQUAL
Reactome Database ID Release 81
10718212
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=10718212
Reactome
R-CEL-381029
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-381029.1
2
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
ACTIVATION
GENE ONTOLOGY
GO:0004674
gene ontology term for cellular function
MI
MI:0355
Same Catalyst Activity
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
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
GENE ONTOLOGY
GO:0036498
gene ontology term for cellular process
MI
MI:0359
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
18038217
Pubmed
2008
Endoplasmic reticulum stress responses
Schröder, Martin
Cell Mol Life Sci 65:862-94
18048764
Pubmed
2008
The role for endoplasmic reticulum stress in diabetes mellitus
Eizirik, DL
Cardozo, AK
Cnop, M
Endocr Rev 29:42-61