UUCD: a family-based database of ubiquitin and ubiquitin-like conjugation

Abstract

In this work, we developed a family-based database of UUCD (http://uucd.biocuckoo.org) for ubiquitin and ubiquitin-like conjugation, which is one of the most important post-translational modifications responsible for regulating a variety of cellular processes, through a similar E1 (ubiquitin-activating enzyme)–E2 (ubiquitin-conjugating enzyme)–E3 (ubiquitin-protein ligase) enzyme thioester cascade. Although extensive experimental efforts have been taken, an integrative data resource is still not available. From the scientific literature, 26 E1s, 105 E2s, 1003 E3s and 148 deubiquitination enzymes (DUBs) were collected and classified into 1, 3, 19 and 7 families, respectively. To computationally characterize potential enzymes in eukaryotes, we constructed 1, 1, 15 and 6 hidden Markov model (HMM) profiles for E1s, E2s, E3s and DUBs at the family level, separately. Moreover, the ortholog searches were conducted for E3 and DUB families without HMM profiles. Then the UUCD database was developed with 738 E1s, 2937 E2s, 46 631 E3s and 6647 DUBs of 70 eukaryotic species. The detailed annotations and classifications were also provided. The online service of UUCD was implemented in PHP + MySQL + JavaScript + Perl.

Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

“…This post-translational modification, referred to as ubiquitination, is catalyzed by sequential actions of three enzymes: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3). Approximately 500 E3 enzymes, each of which is considered to ubiquitinate specific substrate proteins, are encoded in the human genome (56). Ubiquitination regulates the fates or functions of the substrate proteins in multiple ways: it participates in protein degradation in the proteasome, DNA repair, endocytosis and lysosomal trafficking, NFkB signaling and so on (57).…”

Rapid development of proteomics in China: from the perspective of the Human Liver Proteome Project and technology development

“…For example, they manually collected 26 E1s; 105 E2s; 1003 E3s; and 148 deubiquitinating enzymes for ubiquitin and ubiquitin-like conjugation systems in the scientific literature [86]. Also, they classified E3s into a hierarchical structure with five levels, i.e., class, group, subgroup, family, and single E3.…”

Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants

“…However, the maximum diversity is found in the E3 ubiquitin ligase enzymes. There are estimated to be more than 50 E3 ubiquitin ligases in S. cerevisiae, over 600 in humans and over 1000 in Arabidopsis thaliana (Chen and Hellmann 2013, Gao, et al 2013, Michelle, et al 2009). The explanation for this considerable diversity in the E3 ubiquitin ligase family resides in the fact that these proteins are responsible for target protein interaction and must be able to specifically interact with the myriad of protein substrates which are targeted for ubiquitylation.…”

“…Earlier estimates stated that the human genome encodes for approximately 80 functional DUBs (Nijman, et al 2005 (Gao, et al 2013). However, it remains to be established whether all of these genes are functionally expressed and whether they are specific for ubiquitin or ubiquitin-like molecules (i.e.…”

“…As mentioned above, plant genomes contain more than 1000 E3 ubiquitin ligase genes, but in Arabidopsis thaliana, for example, there is only a small family of 7 HECT-containing E3 ubiquitin ligases (Downes, et al 2003, Gao, et al 2013. Moreover, none of these family members share the same C2-WWs-HECT domain architecture as the Nedd4 family.…”