SGTA binds mislocalized membrane protein

Stable Identifier
R-HSA-9617595
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Membrane proteins are not delivered to membranes with complete efficiency and a portion can end up mislocalized to the cytosol. SGTA binds the hydrophobic regions of such mislocalized proteins that are exposed to the cytosol (Leznicki and High 2012, Xu et al. 2012, Wunderly et al. 2014, Shao et al. 2017). Client proteins of SGTA include both tail-anchored proteins destined for insertion into the endoplasmic reticulum membrane (Leznicki et al. 2013) and inappropriately localized proteins such as cytosolic PRNP (PrP) (Leznicki and High 2012), which is normally located in the plasma membrane. Mislocalized proteins bound by SGTA can be routed to the proteasome via ubiquitination by the BAG6 complex (BAG6:GET4:UBL4A) (Shao et al. 2017).

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
23246001 SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation

Xu, Y, Cai, M, Yang, Y, Huang, L, Ye, Y

Cell Rep 2012
23533635 The association of BAG6 with SGTA and tail-anchored proteins

Leznicki, P, Roebuck, QP, Wunderley, L, Clancy, A, Krysztofinska, EM, Isaacson, RL, Warwicker, J, Schwappach, B, High, S

PLoS ONE 2013
25179605 SGTA regulates the cytosolic quality control of hydrophobic substrates

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

J. Cell. Sci. 2014
28104892 Mechanistic basis for a molecular triage reaction

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

Science 2017
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