GET4
Function
As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892, PubMed:32395830). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:25535373, PubMed:28104892). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303).
Involvement in disease
Congenital disorder of glycosylation 2Y
CDG2Y
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2Y is an autosomal recessive form characterized by poor overall growth and global developmental delay with impaired intellectual development. Other features may include hypotonia, seizures, brain imaging abnormalities, dysmorphic features, and various skeletal defects.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated by RNF12, leading to proteasomal degradation. When unassembled from BAG6; ubiquitinylation is modulated by BAG6 quality control role and effectuated by RNF126.
Sequence Similarities
Belongs to the GET4 family.
Cellular localization
- Cytoplasm
- Cytosol
Alternative names
C7orf20, CEE, TRC35, CGI-20, GET4, Golgi to ER traffic protein 4 homolog, Conserved edge-expressed protein, Transmembrane domain recognition complex 35 kDa subunit