This gene encodes a 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 are thus thought to functionally link the ubiquitination machinery to the proteasome to effect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein.
In a small proportion of familial amyotrophic lateral sclerosis (fALS), the UBQLN2 gene is mutated, causing formation of a non-functional Ubiquilin 2 enzyme. This non-functioning enzyme leads to the accumulation of ubiquinated proteins in the lower motor neurons and upper corticospinal motor neurons, due to the fact that ubiquilin 2 normally degrades these ubiquinated proteins, but cannot if the ALS mutation is present. The same accumulations occur in patients without UBQLN2 mutations, but with mutations in other genes, including TDP-43 and C9ORF72.
^Kaye FJ, Modi S, Ivanovska I, Koonin EV, Thress K, Kubo A, Kornbluth S, Rose MD (Mar 2000). "A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch". FEBS Lett. 467 (2–3): 348–55. PMID10675567. doi:10.1016/S0014-5793(00)01135-2.
^Kim TY, Kim E, Yoon SK, Yoon JB (May 2008). "Herp enhances ER-associated protein degradation by recruiting ubiquilins". Biochem. Biophys. Res. Commun. 369 (2): 741–6. PMID18307982. doi:10.1016/j.bbrc.2008.02.086.
^Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (August 2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome". Mol. Cell. 6 (2): 409–19. PMID10983987. doi:10.1016/S1097-2765(00)00040-X.
Murillas R, Simms KS, Hatakeyama S, et al. (2002). "Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligase". J. Biol. Chem. 277 (4): 2897–907. PMID11717310. doi:10.1074/jbc.M110047200.
Walters KJ, Kleijnen MF, Goh AM, et al. (2002). "Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a". Biochemistry. 41 (6): 1767–77. PMID11827521. doi:10.1021/bi011892y.
Saeki Y, Sone T, Toh-e A, Yokosawa H (2002). "Identification of ubiquitin-like protein-binding subunits of the 26S proteasome". Biochem. Biophys. Res. Commun. 296 (4): 813–9. PMID12200120. doi:10.1016/S0006-291X(02)02002-8.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. PMID16713569. doi:10.1016/j.cell.2006.03.032.