hUbiquitome: a database of experimentally verified ubiquitination cascades in humans

Protein ubiquitination is an evolutionarily conserved and functionally diverse post-translational modification achieved through the sequential action of E1-activating enzymes, E2-conjugating enzymes and E3 ligases. A summary of validated ubiquitination substrates have been presented and a prediction of new substrates have been conducted in yeast. However, a systematic summary of human ubiquitination substrates containing experimental evidence and the enzymatic cascade of each substrate is not available. In the present study, hUbiquitome web resource is introduced, a public resource for the retrieval of experimentally verified human ubiquitination enzymes and substrates. hUbiquitome is the first comprehensive database of human ubiquitination cascades. Currently, hUbiquitome has in its repertoire curated data comprising 1 E1 enzyme, 12 E2 enzymes, 138 E3 ligases or complexes, 279 different substrate proteins and 17 deubiquitination enzyme terms. The biological functions of substrates from different kinds of E3s were analyzed using the collected data. The findings show that substrates ubiquitinated by RING (Really Interesting New Gene) E3s are enriched most in apoptosis-related processes, whereas substrates ubiquitinated by other E3s are enriched in gene expression-associated processes. An analysis of the data demonstrates the biological process preferences of the different kinds of E3s. hUbiquitome is the first database to systematically collect experimentally validated ubiquitinated proteins and related ubiquitination cascade enzymes which might be helpful in the field of ubiquitination-modification research. Database URL: http://202.38.126.151/hmdd/hubi/

[1]  M. Isasa,et al.  A new map to understand deubiquitination. , 2010, Biochemical Society transactions.

[2]  A. Sorokin,et al.  Proteasome system of protein degradation and processing , 2009, Biochemistry (Moscow).

[3]  R. Deshaies,et al.  RING domain E3 ubiquitin ligases. , 2009, Annual review of biochemistry.

[4]  Ying Zhang,et al.  DUBs and cancer: The role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors , 2009, Cell cycle.

[5]  A. Ciechanover,et al.  Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. , 2009, Annual review of pharmacology and toxicology.

[6]  Patrick G. A. Pedrioli,et al.  Using mass spectrometry to identify ubiquitin and ubiquitin‐like protein conjugation sites , 2009, Proteomics.

[7]  Dongsup Kim,et al.  SCUD: Saccharomyces Cerevisiae Ubiquitination Database , 2008, BMC Genomics.

[8]  Lan Huang,et al.  Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. , 2008, Journal of proteome research.

[9]  Aaron Ciechanover,et al.  The HECT family of E3 ubiquitin ligases: multiple players in cancer development. , 2008, Cancer cell.

[10]  Hodong Lee,et al.  E3Miner: a text mining tool for ubiquitin-protein ligases , 2008, Nucleic Acids Res..

[11]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[12]  Alejandro Garcia,et al.  UbiProt: a database of ubiquitylated proteins , 2007, BMC Bioinformatics.

[13]  A. Ciechanover,et al.  Narrative Review: Protein Degradation and Human Diseases: The Ubiquitin Connection , 2006, Annals of Internal Medicine.

[14]  René Bernards,et al.  A Genomic and Functional Inventory of Deubiquitinating Enzymes , 2005, Cell.

[15]  C. Borchers,et al.  Mass spectrometric determination of protein ubiquitination. , 2005, Methods in molecular biology.

[16]  Aaron Ciechanover,et al.  Proteolysis: from the lysosome to ubiquitin and the proteasome , 2005, Nature Reviews Molecular Cell Biology.

[17]  A. Amerik,et al.  Mechanism and function of deubiquitinating enzymes. , 2004, Biochimica et biophysica acta.

[18]  C. Pickart,et al.  Ubiquitin: structures, functions, mechanisms. , 2004, Biochimica et biophysica acta.

[19]  Timothy Cardozo,et al.  The SCF ubiquitin ligase: insights into a molecular machine , 2004, Nature Reviews Molecular Cell Biology.

[20]  K. Nakayama,et al.  U-box proteins as a new family of ubiquitin ligases. , 2003, Biochemical and biophysical research communications.

[21]  D. Ganem,et al.  PHD domains and E3 ubiquitin ligases: viruses make the connection. , 2003, Trends in cell biology.

[22]  C. Pickart,et al.  Mechanisms underlying ubiquitination. , 2001, Annual review of biochemistry.

[23]  A. Ciechanover,et al.  The ubiquitin‐mediated proteolytic pathway: Mode of action and clinical implications , 2000, Journal of cellular biochemistry. Supplement.

[24]  M. Hochstrasser,et al.  The Saccharomyces cerevisiae ubiquitin-proteasome system. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.