Ubiquilin 1: Proteins and Enzymes
Ubiquilin 1 is a ubiquitously expressed member of the UBL-UBA family of Ubiquitin-binding proteins that is 589 amino acids (aa) in length and has a predicted molecular weight of 62.5 kDa. Human Ubiquilin 1 shares 88% aa sequence identity with the mouse and rat orthologs. It contains an N-terminal Ubiquitin-like (UBL) domain and a C-terminal Ubiquitin-associated (UBA) domain. The UBA domain is able to interact with mono- and poly-Ubiquitin chains, with a similar affinity for Lys48- and Lys63-linked chains. In contrast, the UBL domain interacts with Ubiquitin-interacting motif (UIM)-containing proteins, such as S5a/Angiocidin, a 19S Proteasome component. It is thought that Ubiquilin 1 may act as a molecular shuttle, bringing poly-ubiquitinated proteins to the 26S Proteasome by simultaneously binding poly-Ubiquitin via its UBA domain and the 19S Proteasome via its UBL domain. Ubiquilin 1 also binds two endoplasmic reticulum (ER)-localized proteins, Herp and Erasin, and may function in the ER-associated degradation pathway. It has been reported to co-precipitate with LC3/MAP1LC3A/Apg8p3, an autophagosomal marker, suggesting that it may play a role in autophagy. Single nucleotide polymorphisms in the UBQLN1 gene have been linked to Alzheimer’s disease (AD). Furthermore, Ubiquilin 1 may regulate the processing of APP, which is associated with AD.
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Ubiquilin 1: Proteins and Enzymes
Ubiquilin 1 is a ubiquitously expressed member of the UBL-UBA family of Ubiquitin-binding proteins that is 589 amino acids (aa) in length and has a predicted molecular weight of 62.5 kDa. Human Ubiquilin 1 shares 88% aa sequence identity with the mouse and rat orthologs. It contains an N-terminal Ubiquitin-like (UBL) domain and a C-terminal Ubiquitin-associated (UBA) domain. The UBA domain is able to interact with mono- and poly-Ubiquitin chains, with a similar affinity for Lys48- and Lys63-linked chains. In contrast, the UBL domain interacts with Ubiquitin-interacting motif (UIM)-containing proteins, such as S5a/Angiocidin, a 19S Proteasome component. It is thought that Ubiquilin 1 may act as a molecular shuttle, bringing poly-ubiquitinated proteins to the 26S Proteasome by simultaneously binding poly-Ubiquitin via its UBA domain and the 19S Proteasome via its UBL domain. Ubiquilin 1 also binds two endoplasmic reticulum (ER)-localized proteins, Herp and Erasin, and may function in the ER-associated degradation pathway. It has been reported to co-precipitate with LC3/MAP1LC3A/Apg8p3, an autophagosomal marker, suggesting that it may play a role in autophagy. Single nucleotide polymorphisms in the UBQLN1 gene have been linked to Alzheimer’s disease (AD). Furthermore, Ubiquilin 1 may regulate the processing of APP, which is associated with AD.
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