1j8c

Structural highlights

Disease

UBQL2_HUMAN Defects in UBQLN2 are the cause of amyotrophic lateral sclerosis type 15 with or without frontotemporal dementia (ALS15) [MIM:300857. 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.^{[1] [2] [3] [4]}

Function

UBQL2_HUMAN Increases the half-life of proteins destined to be degraded by the proteasome; may modulate proteasome-mediated protein degradation.^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ 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. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature. 2011 Aug 21;477(7363):211-5. doi: 10.1038/nature10353. PMID:21857683 doi:10.1038/nature10353
2. ↑ Synofzik M, Maetzler W, Grehl T, Prudlo J, Vom Hagen JM, Haack T, Rebassoo P, Munz M, Schols L, Biskup S. Screening in ALS and FTD patients reveals 3 novel UBQLN2 mutations outside the PXX domain and a pure FTD phenotype. Neurobiol Aging. 2012 Dec;33(12):2949.e13-7. doi:, 10.1016/j.neurobiolaging.2012.07.002. Epub 2012 Aug 11. PMID:22892309 doi:10.1016/j.neurobiolaging.2012.07.002
3. ↑ Williams KL, Warraich ST, Yang S, Solski JA, Fernando R, Rouleau GA, Nicholson GA, Blair IP. UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis. Neurobiol Aging. 2012 Oct;33(10):2527.e3-10. doi:, 10.1016/j.neurobiolaging.2012.05.008. Epub 2012 Jun 19. PMID:22717235 doi:10.1016/j.neurobiolaging.2012.05.008
4. ↑ Daoud H, Suhail H, Szuto A, Camu W, Salachas F, Meininger V, Bouchard JP, Dupre N, Dion PA, Rouleau GA. UBQLN2 mutations are rare in French and French-Canadian amyotrophic lateral sclerosis. Neurobiol Aging. 2012 Sep;33(9):2230.e1-2230.e5. doi:, 10.1016/j.neurobiolaging.2012.03.015. Epub 2012 May 3. PMID:22560112 doi:10.1016/j.neurobiolaging.2012.03.015
5. ↑ Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell. 2000 Aug;6(2):409-19. PMID:10983987