UBQLN2

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 Hspa13 (Stch) protein.

Human UBQLN2 shares a high degree of similarity with related ubiquilins including UBQLN1 and UBQLN4.{{cite journal | author = Marín I | title = The ubiquilin gene family: evolutionary patterns and functional insights | journal = BMC Evol Biol | volume = 14| pages = 63 | date=March 2014 | issue = 1 | pmid = 24674348 | doi = 10.1186/1471-2148-14-63 | pmc=4230246 | bibcode = 2014BMCEE..14...63M | doi-access = free }}

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.{{cite journal |vauthors=Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL, Mugnaini E, Pericak-Vance MA, Siddique T | title = Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia | journal = Nature | volume = 477| issue = 7363| pages = 211–215|date=August 2011 | pmid = 21857683 | doi = 10.1038/nature10353 | pmc=3169705| bibcode = 2011Natur.477..211D }}

• {{cite news |author=Amanda Schaffer |date=August 29, 2011 |title=Possible Culprit Is Found for Lou Gehrig's Disease |newspaper=The New York Times |url=https://www.nytimes.com/2011/08/30/health/30theory.html |url-access=subscription}} The same accumulations occur in patients without UBQLN2 mutations, but with mutations in other genes, including TDP-43 and C9ORF72.{{Citation needed|date=November 2021}}

UBQLN2 has been shown to interact with HERPUD1{{cite journal |vauthors=Kim TY, Kim E, Yoon SK, Yoon JB | title = Herp enhances ER-associated protein degradation by recruiting ubiquilins | journal = Biochem. Biophys. Res. Commun. | volume = 369 | issue = 2 | pages = 741–6 |date=May 2008 | pmid = 18307982 | doi = 10.1016/j.bbrc.2008.02.086 }} and UBE3A.{{cite journal |vauthors=Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM | title = The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome | journal = Mol. Cell | volume = 6 | issue = 2 | pages = 409–19 |date=August 2000 | pmid = 10983987 | doi = 10.1016/S1097-2765(00)00040-X | doi-access = free }}

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