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. 2018 Jan 4;46(D1):D447-D453.
doi: 10.1093/nar/gkx1041.

iUUCD 2.0: an update with rich annotations for ubiquitin and ubiquitin-like conjugations

Jiaqi Zhou  1 , Yang Xu  1 , Shaofeng Lin  1 , Yaping Guo  1 , Wankun Deng  1 , Ying Zhang  1 , Anyuan Guo  1 , Yu Xue  1
Affiliations

iUUCD 2.0: an update with rich annotations for ubiquitin and ubiquitin-like conjugations

Jiaqi Zhou et al. Nucleic Acids Res. .

Abstract

Here, we described the updated database iUUCD 2.0 (http://iuucd.biocuckoo.org/) for ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), ubiquitin-protein ligases (E3s), deubiquitinating enzymes (DUBs), ubiquitin/ubiquitin-like binding domains (UBDs) and ubiquitin-like domains (ULDs), which act as key regulators in modulating ubiquitin and ubiquitin-like (UB/UBL) conjugations. In total, iUUCD 2.0 contained 136 512 UB/UBL regulators, including 1230 E1s, 5636 E2s, 93 343 E3s, 9548 DUBs, 30 173 UBDs and 11 099 ULDs in 148 eukaryotic species. In particular, we provided rich annotations for regulators of eight model organisms, especially in humans, by compiling and integrating the knowledge from nearly 70 widely used public databases that cover cancer mutations, single nucleotide polymorphisms (SNPs), mRNA expression, DNA and RNA elements, protein-protein interactions, protein 3D structures, disease-associated information, drug-target relations, post-translational modifications, DNA methylation and protein expression/proteomics. Compared with our previously developed UUCD 1.0 (∼0.41 GB), iUUCD 2.0 has a size of ∼32.1 GB of data with a >75-fold increase in data volume. We anticipate that iUUCD 2.0 can be a more useful resource for further study of UB/UBL conjugations.

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Figures

Figure 1.
Figure 1.
The procedure for the construction of the iUUCD 2.0 database. First, we searched PubMed to collect experimentally identified UB/UBL regulators. Then, we classified known regulators into distinct families and constructed HMM profiles for each family if available. For families without HMM profiles, we also conducted an orthologous search to ensure data integrity. In addition to basic annotations, we further mapped all regulators in eight model organisms, especially in Homo sapiens, to nearly 70 public databases that covered each of 11 aspects: (i) cancer mutations, (ii) SNPs, (iii) mRNA expressions, (iv) DNA and RNA elements, (v) PPIs, (vi) protein 3D structures, (vii) disease-associated information, (viii) drug-target relations, (ix) PTMs, (x) DNA methylation and (xi) protein expression/proteomics.
Figure 2.
Figure 2.
The classification of UB/UBL regulators together with the cut-off values of the 58 HMM profiles for E1, E2, E3, DUB, UBD and ULD families. The hmmsearch program calculates both the E-values and log-odds likelihood scores for given protein sequences. Since the E-values depend on the database size and generate inconsistent results when the database is updated, we used realistic constant log-odds likelihood scores as the threshold values.
Figure 3.
Figure 3.
Browsing the iUUCD 2.0. (A) The option to browse by species. (B) The option to browse by classification. The members of the human E3 activity/RING/RING family are shown in a tabular format. (C) The basic information on human MDM2 in the results page. (D) The multi-layer annotations of human MDM2.
Figure 4.
Figure 4.
The overview of multiple-layer annotations of human MDM2 integrated in iUUCD 2.0. A brief summary of the 67 additional public databases is given in Supplementary Table S5.
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