USP53 explained

Inactive ubiquitin carboxyl-terminal hydrolase 53 is a protein that in humans is encoded by the USP53 gene.^[1]

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.^{[2] [3] [4]} 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,^[4] as well as late-onset hearing loss and cholestasis in humans.^[5] USP53 localizes at cellular tight junctions and interacts with tight junction protein 2 (TJP2).^[4] Mutations in TJP2 have also been shown to cause hearing impairments^[6] and cholestasis.^[7]

Further reading

• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Ozyildirim AM, Wistow GJ, Gao J, Wang J, Dickinson DP, Frierson HF, Laurie GW . The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts . Investigative Ophthalmology & Visual Science . 46 . 5 . 1572–80 . May 2005 . 15851553 . 10.1167/iovs.04-1380 . 10.1.1.123.3574 .

Notes and References

1. Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O . Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 7 . 1 . 65–73 . February 2000 . 10718198 . 10.1093/dnares/7.1.65 . free .
2. Quesada V, Díaz-Perales A, Gutiérrez-Fernández A, Garabaya C, Cal S, López-Otín C . Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases . Biochemical and Biophysical Research Communications . 314 . 1 . 54–62 . January 2004 . 14715245 . 10.1016/j.bbrc.2003.12.050 .
3. Web site: Entrez Gene: USP53 ubiquitin specific peptidase 53.
4. Kazmierczak M, Harris SL, Kazmierczak P, Shah P, Starovoytov V, Ohlemiller KK, Schwander M . Progressive Hearing Loss in Mice Carrying a Mutation in Usp53 . The Journal of Neuroscience . 35 . 47 . 15582–98 . November 2015 . 26609154 . 4659823 . 10.1523/JNEUROSCI.1965-15.2015 .
5. Maddirevula S, Alhebbi H, Alqahtani A, Algoufi T, Alsaif HS, Ibrahim N, Abdulwahab F, Barr M, Alzaidan H, Almehaideb A, AlSasi O, Alhashem A, Hussaini HA, Wali S, Alkuraya FS . Identification of novel loci for pediatric cholestatic liver disease defined by KIF12, PPM1F, USP53, LSR, and WDR83OS pathogenic variants. . Genetics in Medicine . September 2018 . 21 . 5 . 1164–1172 . 10.1038/s41436-018-0288-x . 30250217 . 52811525 . free .
6. Wang HY, Zhao YL, Liu Q, Yuan H, Gao Y, Lan L, Yu L, Wang DY, Guan J, Wang QJ . Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment . Chinese Medical Journal . 128 . 24 . 3345–51 . December 2015 . 26668150 . 4797511 . 10.4103/0366-6999.171440 . free .
7. Sambrotta M, Strautnieks S, Papouli E, Rushton P, Clark BE, Parry DA, Logan CV, Newbury LJ, Kamath BM, Ling S, Grammatikopoulos T, Wagner BE, Magee JC, Sokol RJ, Mieli-Vergani G, Smith JD, Johnson CA, McClean P, Simpson MA, Knisely AS, Bull LN, Thompson RJ. Mutations in TJP2 cause progressive cholestatic liver disease . Nature Genetics . 46 . 4 . 326–328. October 2014 . 24614073 . 4061468 . 10.1038/ng.2918.