UBQLN1

This gene encodes an ubiquitin-like protein (ubiquilin) that shares a high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain an 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 modulate accumulation of presenilin proteins, and it is found in lesions associated with Alzheimer's and Parkinson's disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Ubiquilin 1

Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and 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:15147878).
Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:19822669, 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, PubMed:23459205).
Negatively regulates the TICAM1/TRIF-dependent toll-like receptor signaling pathway by decreasing the abundance of TICAM1 via the autophagic pathway (PubMed:21695056).
Promotes the ubiquitination and lysosomal degradation of ORAI1, consequently down-regulating the ORAI1-mediated Ca2+ mobilization (PubMed:23307288).
Suppresses the maturation and proteasomal degradation of amyloid beta A4 protein (A4) by stimulating the lysine 63 (K63)-linked polyubiquitination. Delays the maturation of A4 by sequestering it in the Golgi apparatus and preventing its transport to the cell surface for subsequent processing (By similarity).
Ubiquitinates BCL2L10 and thereby stabilizes protein abundance (PubMed:22233804).
Isoform 1
Plays a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress (PubMed:18953672).
Plays a key role in the regulation of the levels of PSEN1 by targeting its accumulation to aggresomes which may then be removed from cells by autophagocytosis (PubMed:21143716).
Isoform 2
Plays a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress.
Isoform 3
Plays a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress (PubMed:18953672).
Plays a key role in the regulation of the levels of PSEN1 by targeting its accumulation to aggresomes which may then be removed from cells by autophagocytosis (PubMed:21143716).

Biological Process aggrephagy Source:UniProtKB1 Publication
Biological Process autophagosome assembly Source:GO_Central1 Publication
Biological Process autophagosome maturation Source:GO_Central1 Publication
Biological Process cellular response to hypoxia Source:BHF-UCL1 Publication
Biological Process macroautophagy Source:GO_Central1 Publication
Biological Process negative regulation of store-operated calcium channel activity Source:UniProtKB1 Publication
Biological Process negative regulation of toll-like receptor 3 signaling pathway Source:Ensembl
Biological Process positive regulation of ER-associated ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication
Biological Process positive regulation of protein ubiquitination Source:UniProtKB1 Publication
Biological Process regulation of macroautophagy Source:GO_Central1 Publication
Biological Process regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source:BHF-UCL1 Publication
Biological Process regulation of protein ubiquitination Source:HGNC-UCL1 Publication
Biological Process response to endoplasmic reticulum stress Source:BHF-UCL1 Publication
Biological Process ubiquitin-dependent ERAD pathway Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:GO_Central1 Publication

Cytoplasm
Nucleus
Endoplasmic reticulum
Cytoplasmic vesicle, autophagosome
Cell membrane
Detected in neuronal processes and at synapses (By similarity).
Recruited to the ER during ER-associated protein degradation (ERAD) (PubMed:19822669).
Isoform 1 and isoform 3 colocalize with PSEN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes (PubMed:21143716).
Colocalizes with ORAI1 and TICAM1 in the autophagosome (PubMed:23307288, PubMed:21695056).
Colocalizes with EPS15 and HGS in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments and with EPS15 also in aggresomes (PubMed:16159959).

Degraded during both macroautophagy and during chaperone-mediated autophagy (CMA).
Phosphorylated.
Ubiquitinated.