BAG6:GET4:UBL4A binds mislocalized membrane protein:SGTA and ASNA1:ATP

Stable Identifier
R-HSA-9617596
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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SGTA is believed to initially bind exposed hydrophobic regions of proteins (client proteins) in the cytosol and then associate with the BAG6 complex (BAG6:GET4:UBL4A) and ASNA1 (Mariappan et al. 2010, Hessa et al. 2011, Leznicki et al. 2012, Wunderly et al. 2014, Shao et al. 2017). If the client protein is not efficiently transferred to ASNA1 then the client protein is transferred to BAG6 (Shao et al. 2017), which has been demonstrated to bind hydrophobic regions of proteins and appears to prevent their aggregation prior to proteasomal degradation (Wang et al. 2011). The efficiency of transfer of a client protein to ASNA1 appears to be determined by the sequence of the hydrophobic domain (Hessa et al. 2011). SGTA is not a stable component of the BAG6 complex (Marriapan et al. 2010) and SGTA and RNF126 compete for the same binding site on BAG6 (Krysztofinska et al. 2016).

Literature References
PubMed ID Title Journal Year
23129660 SGTA antagonizes BAG6-mediated protein triage

Leznicki, P, High, S

Proc. Natl. Acad. Sci. U.S.A. 2012
21636303 A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation

Wang, Q, Liu, Y, Soetandyo, N, Baek, K, Hegde, R, Ye, Y

Mol. Cell 2011
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
28104892 Mechanistic basis for a molecular triage reaction

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

Science 2017
25179605 SGTA regulates the cytosolic quality control of hydrophobic substrates

Wunderley, L, Leznicki, P, Payapilly, A, High, S

J. Cell. Sci. 2014
21743475 Protein targeting and degradation are coupled for elimination of mislocalized proteins

Hessa, T, Sharma, A, Mariappan, M, Eshleman, HD, Gutierrez, E, Hegde, RS

Nature 2011
27193484 Structural and functional insights into the E3 ligase, RNF126

Krysztofinska, EM, Martínez-Lumbreras, S, Thapaliya, A, Evans, NJ, High, S, Isaacson, RL

Sci Rep 2016
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