Ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3)
The protein contains 230 amino acids for an estimated molecular weight of 26183 Da.
Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3'', and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. (updated: Oct. 16, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 603090
Ubiquitin carboxyl-terminal esterase l3; uchl3
CLONING
Covalent attachment of the C terminus of ubiquitin (191339) to cellular proteins plays a role in a variety of cellular processes. Ubiquitin C-terminal hydrolysis is catalyzed by deubiquitinating (DUB) enzymes and is necessary for several functions, including liberation of monomeric ubiquitin from the precursors encoded by ubiquitin genes and recycling of ubiquitin monomers. There are 2 distinct families of DUBs, ubiquitin-specific proteases (UBPs) and ubiquitin C-terminal hydrolases (UCHs). Mayer and Wilkinson (1989) identified 4 distinct UCH activities from bovine thymus. All 4 were thiol proteases and had high-affinity binding sites for ubiquitin. Wilkinson et al. (1989) purified the predominant isozyme, UCHL3, and raised antibodies against it. By screening a human B-cell expression library with the antibodies, the authors isolated cDNAs encoding human UCHL3. The predicted 230-amino acid human UCHL3 protein is 54% identical to UCHL1 (191342). Using Northern blot analysis, Kurihara et al. (2002) found that mouse Uchl3 was expressed at all embryonic stages examined, beginning at embryonic day 7. In adult tissues, Uchl3 was variably expressed in all tissues examined, with highest expression in testis.GENE FUNCTION
Wilkinson et al. (1989) showed that recombinant UCHL3 protein displayed UCH activity in vitro.BIOCHEMICAL FEATURES
Johnston et al. (1997) determined the crystal structure of human UCHL3.GENE STRUCTURE
Kurihara et al. (2002) determined that the 5-prime ends of the mouse and human UCHL3 genes contain a conserved CpG island.MAPPING
By genomic sequence analysis, Kurihara et al. (2002) mapped the UCHL3 gene to a region of human chromosome 13q22. The mouse Uchl3 gene maps to a syntenic region on chromosome 14.ANIMAL MODEL
Altered function of the ubiquitin pathway has been implicated in the etiology of neurodegeneration. For example, Saigoh et al. (1999) showed that gracile axonal dystrophy (gad) mutant mice, which harbor a deletion within the gene encoding ubiquitin C-terminal hydrolase L1 (UCHL1; 191342), display sensory ataxia followed by posterior paralysis and lethality. However, mice homozygous for a targeted deletion of the related Uchl3 gene are indistinguishable from wildtype (Kurihara et al., 2000). To assess whether the 2 hydrolases have redundant function, Kurihara et al. (2001) generated mice homozygous for both Uchl1(gad) and Uchl3(delta3-7). The double homozygotes weighed 30% less than single homozygotes and displayed an earlier onset of lethality, possibly due to dysphagia. Axonal degeneration of the nucleus tractus solitarius and area postrema of the medulla was noted in these mice. The double homozygotes also displayed a more severe axonal degeneration of the gracile tract of the medulla and spinal cord than had been observed in Uchl1(gad) single homozygotes. In addition, degeneration of dorsal root ganglia cell bodies was detected in both the double homozygotes and Uchl3(delta3-7) single homozygotes. Given that both Uchl1(gad) and Uchl3(delta3-7) single homozygotes displayed distinct degenerative defects that were exacerbated in the double homozygotes, the authors concluded that Uchl1 and Uchl3 may have both separate and overlapping functions in the maintenance of neurons of the gracile tract, nucleus tractus solitarius, and area postrema. The Acrg minimal region is a 1.5- to 1.7-Mb domain defined by genetic complementation among deletion ... More on the omim web site
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603090 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed