Although USP53 is classified as a deubiquitinating enzyme based on sequence homology to other proteases from this group, it lacks a functionally essential histidine in the catalytic domaine and activity assays suggest that USP53 is catalytically inactive.
[6][7][8] Even though USP53 is devoid of catalytic activity, USP53 serves important physiological functions:
mutations in Usp53 have been shown to cause progressive hearing loss in mice,[8] as well as late-onset hearing loss and cholestasis in humans.[9]
USP53 localizes at cellular tight junctions and interacts with tight junction protein 2 (TJP2).[8] Mutations in TJP2 have also been shown to cause hearing impairments[10] and cholestasis.[11]
^Quesada V, Díaz-Perales A, Gutiérrez-Fernández A, Garabaya C, Cal S, López-Otín C (January 2004). "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases". Biochemical and Biophysical Research Communications. 314 (1): 54–62. doi:10.1016/j.bbrc.2003.12.050. PMID14715245.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID16189514. S2CID4427026.
Ozyildirim AM, Wistow GJ, Gao J, Wang J, Dickinson DP, Frierson HF, Laurie GW (May 2005). "The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts". Investigative Ophthalmology & Visual Science. 46 (5): 1572–80. CiteSeerX10.1.1.123.3574. doi:10.1167/iovs.04-1380. PMID15851553.
