NAR Molecular Biology Database Collection entry number 68
Xue, Yu; Zhou, Jiaqi; Xu, Yang ,; Lin, Shaofeng; Guo, Yaping; Deng, Wankun; Zhang, Ying.; Guo, Anyuan
1 Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China

Database Description

The ubiquitin and ubiquitin-like (Ub/Ubl) conjugation is one of the most important post- translational modifications (PTMs) in proteins, and regulates a large number of cellular processes, such as cell cycle, signal transduction, apoptosis and autophagy, while aberrant modification is implicated in numerous pathologies, such as neurodegenerative disorders, inflammatory diseases and cancers. Identification and annotation of regulators in Ub/Ubl systems is fundamental for understanding the molecular mechanisms of Ub/Ubl conjugations, and provides a highly useful reservoir for discovering disease biomarkers and drug targets. In 2013, we reported a family-based database of UUCD 1.0 for ubiquitin and ubiquitin-like conjugations, containing 738 ubiquitin-activating enzyme (E1s), 2,937 ubiquitin-conjugating enzymes (E2s), 46,631 ubiquitin-protein ligases (E3s) and 6,647 deubiquitinating enzymes (DUBs) in 70 eukaryotes (1), whereas proteins with ubiquitin domains (UBDs) and ubiquitin-like domains (ULDs) were not included at that time (2,3). In this update, we greatly improved our previous database, and provided a much more comprehensive resource of iUUCD 2.0 (http://iuucd.biocuckoo.org/). Firstly, 27 E1s, 109 E2s, 1,153 E3s, 164 DUBs, 396 UBDs and 183 ULDs were collected from scientific literatures and classified into 1, 4, 23, 8, 27, 11 families, respectively. Secondly, HMM identification and ortholog search were adopted to detect the potential regulators. Ultimately, the iUUCD 2.0 totally contains 136,512 regulators in ubiquitin and ubiquitin-like conjugation systems, including 1,230 E1s, 5,636 E2s, 93,343 E3s, 9,548 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 (i) Cancer Mutations, including ICGC, COSMIC, TCGA, CGAP and IntOGen; (ii) Single Nucleotide Polymorphisms (SNPs), such as dbSNP; (iii) mRNA Expression, including GEO, ArrayExpress, GXD, FFGED, TCGA, ICGC, COSMIC, HUMAN PROTEOME MAP and The Human Protein Atlas; (iv) DNA and RNA Elements, including UTRdb, AREsite, JASPAR CORE, circBase, circRNADb, CircNet, Circ2Traits, miRTarBase, microRNA.org, TRANSFAC, miRWalk, TargetScan, miRecords, RepTar, miRNAMap, SomamiR DB 2.0, miRcode, RAID v2.0 and LncRNADisease; (v) Protein- protein Interactions (PPIs), including IID, iRefIndex, PINA, HINT, Mentha, SZDB and InWeb_IM; (vi) Protein 3D Structures, including PDB, MMDB and SCOP; (vii) Disease-associated information, including ClinVar, OMIM, GWASdb and GWAS CENTRAL; (viii) Drug-target Relations, including DrugBank, TTD, KPID, CARLSBAD, SuperTarget, GRAC and PDTD; (ix) Post-translational Modifications (PTMs), including CPLM, dbPAF, dbPPT, phosSNP, PhosphositePlus, Phospho.ELM, dbPTM, PHOSIDA, BioGRID, HPRD, UniProt, O-GlycBase, PhosphoBase and mUbiSiDa; (x) DNA Methylation, including MethyCancer, TCGA, ICGC and COSMIC; (xi) Protein Expression/Proteomics, including The Human Protein Atlas, Human Proteome Map and GPMDB. 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 expect that iUUCD 2.0 can be more useful for further study of ubiquitin and ubiquitin-like conjugations.


The authors thank Yaru Miao for her helpful comments during the database construction. American Journal Experts reviewed the manuscript prior to submission.


1. Gao, T., Liu, Z., Wang, Y., Cheng, H., Yang, Q., Guo, A., Ren, J. and Xue, Y. (2013) UUCD: a family-based database of ubiquitin and ubiquitin-like conjugation. Nucleic Acids Research, 41, D445-451.
2. Buchberger, A. (2002) From UBA to UBX: new words in the ubiquitin vocabulary. Trends in Cell Biology, 12, 216-221.
3. Hochstrasser, M. (2000) Evolution and function of ubiquitin-like protein-conjugation systems. Nature Cell Biology, 2, E153-157.

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