UniProt functional annotation for P11441

UniProt code: P11441.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
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). 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:28104892, PubMed:25535373). 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). {ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:28104892}.
 
Subunit: Component of the BAG6/BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35 (PubMed:20676083, PubMed:25535373). Interacts with BAG6; the interaction is direct and required for UBL4A protein stability (PubMed:25713138, PubMed:25535373). Interacts with USP13; may be indirect via BAG6 (PubMed:24424410). {ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:25713138}.
Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303}. Nucleus {ECO:0000269|PubMed:21636303}.
Ptm: Polyubiquitinated. Ubiquitination by AMFR and deubiquitination by USP13 may regulate the interaction between the BAG6/BAT3 complex and SGTA and therefore may regulate client proteins fate. {ECO:0000269|PubMed:24424410}.

Annotations taken from UniProtKB at the EBI.