ATF6:HSPA5 (ATF6-alpha:BiP) dissociates and HSPA5 binds unfolded protein

Stable Identifier
R-HSA-381158
Type
Reaction [transition]
Species
Homo sapiens
Compartment
endoplasmic reticulum membrane, endoplasmic reticulum lumen
ReviewStatus
5/5
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ATF6:HSPA5 (ATF6-alpha:BiP) dissociates and HSPA5 binds unfolded protein
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ATF6-alpha is a transmembrane protein located in the endoplasmic reticulum (ER) membrane with N-terminal cytoplasmic and C-terminal luminal domains. BiP binds the luminal domain of ATF6-alpha via the substrate binding domain of BiP. Binding of BiP blocks 2 Golgi localization sequences on ATF6-alpha, maintaining ATF6-alpha in the ER.
BiP is also a general chaperone capable of binding unfolded proteins in the ER lumen. When chaperone activity in the ER is overwhelmed, BiP dissociates from ATF6-alpha and binds the excess unfolded proteins. It is unclear whether the dissociation is due to competition of unfolded proteins for BiP or to a more specific interaction between BiP and ATF6-alpha. The dissociation exposes the Golgi localization sequences of ATF6-alpha and allows ATF6-alpha to transit to the Golgi.
Literature References
PubMed ID Title Journal Year
12110171 ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals

Hendershot, L, Chen, X, Shen, J, Prywes, R

Dev Cell 2002
15657421 Stable binding of ATF6 to BiP in the endoplasmic reticulum stress response

Lippincott-Schwartz, J, Shen, J, Prywes, R, Snapp, EL

Mol Cell Biol 2005
11821395 The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi

Chen, X, Shen, J, Prywes, R

J Biol Chem 2002
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Orthologous Events
ATF6B:HSPA5 (ATF6-beta:BiP) dissociates and HSPA5 binds unfolded protein (Homo sapiens)
Authored
May, B  (2009-06-02)
Reviewed
Gillespie, ME  (2008-12-02)
D'Eustachio, P  (2008-12-02)
Matthews, L  (2008-12-02)
Urano, F  (2010-04-30)
Created
May, B  (2008-11-19)
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