Tail-anchored protein:SGTA:BAG6:GET4:UBL4A:ASNA1:ATP dissociates and ASNA1 hydrolyzes ATP yielding Tail-anchored protein:ASNA1:ADP

Stable Identifier
R-HSA-9609860
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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A properly folded tail-anchored (TA) protein is transferred from SGTA to ASNA1 via the BAG6 complex (BAG6:UBL4A:GET4 also known at BAT3:GET5:TRC35) (Marriapan et al. 2010, Leznicki et al. 2011, Mock et al. 2015, Shao et al. 2017, Guna et al. 2018). The TA protein bound to ASNA1 is then presumed to dissociate from the BAG6 complex (inferred from yeast homologs). At some point during or shortly after dissociation, ASNA1 hydrolyzes bound ATP to yield ADP (inferred from yeast homologs).
Improperly folded proteins and improperly localized hydrophobic proteins are transferred from SGTA to BAG6 rather than to ASNA1 (Shao et al. 2017). BAG6 then recruits RNF126 and facilitates the ubiquitination and consequent degradation of the defective protein. The selection of transferring a substrate protein from SGTA to ASNA1 or to BAG6 thereby acts as a "molecular triage". Proteins with less hydrophobic tail-anchors appear to be inserted into the endoplasmic reticulum membrane by a separate system comprising calmodulin and the ER membrane protein complex (Guna et al. 2018).

Literature References
PubMed ID Title Journal Year
20676083 A ribosome-associating factor chaperones tail-anchored membrane proteins

Mariappan, M, Li, X, Stefanovic, S, Sharma, A, Mateja, A, Keenan, RJ, Hegde, RS

Nature 2010
29242231 The ER membrane protein complex is a transmembrane domain insertase

Guna, A, Volkmar, N, Christianson, JC, Hegde, RS

Science 2018
25535373 Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain

Mock, JY, Chartron, JW, Zaslaver, M, Xu, Y, Ye, Y, Clemons, WM

Proc. Natl. Acad. Sci. U.S.A. 2015
28104892 Mechanistic basis for a molecular triage reaction

Shao, S, Rodrigo-Brenni, MC, Kivlen, MH, Hegde, RS

Science 2017
21466504 A biochemical analysis of the constraints of tail-anchored protein biogenesis

Leznicki, P, Warwicker, J, High, S

Biochem. J. 2011
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Catalyst Activity
Title
ATPase activity of Tail-anchored protein:ASNA1:ATP [cytosol]
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