UBQLN2

This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases; and thus, are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein. [provided by RefSeq, Oct 2009]

Ubiquilin-2

Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (PubMed:10983987).
Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:24215460, PubMed:18307982).
Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:19148225, PubMed:20529957).
Negatively regulates the endocytosis of GPCR receptors: AVPR2 and ADRB2, by specifically reducing the rate at which receptor-arrestin complexes concentrate in clathrin-coated pits (CCPs) (PubMed:18199683).

Biological Process autophagosome assembly Source:GO_Central1 Publication
Biological Process negative regulation of clathrin-dependent endocytosis Source:UniProtKB1 Publication
Biological Process negative regulation of G protein-coupled receptor internalization Source:UniProtKB1 Publication
Biological Process positive regulation of ER-associated ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication
Biological Process regulation of autophagosome assembly Source:UniProtKB1 Publication
Biological Process regulation of macroautophagy Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent ERAD pathway Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:GO_Central1 Publication

Cytoplasm
Nucleus
Membrane
Cytoplasmic vesicle, autophagosome
Colocalizes with a subset of proteasomes, namely those that are cytoskeleton associated or free in the cytosol. Associated with fibers in mitotic cells.

Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (ALS15):
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia.

Degraded during macroautophagy.