Abstract: Ubiquitin is a small-molecule protein composed of 76 amino acids. The covalent-bonding process between ubiquitin and substrates is defined as Ubiquitination. Ubiquitination modification, an efficient, ATP-dependent, and highly specific process, is mediated by a cascade regulation of ubiquitin activating enzymes, ubiquitin conjugating enzymes, ubiquitin ligase and deubiquitinating enzymes. Ubiquitination is highly relevant with biological processes like cell cycle regulation, cell apoptosis, transcription regulation, DNA damage response and so on. In the process of ubiquitination, the recognition between ubiquitin ligases and substrates is critical for the specificity. The mechanisms of such recognition are being reported moreover the high throughput methods identifying E3’s substrate are being improved and developed. With the accumulation of ubiquitination data from the deep-going research, the bioinformatics approach studying the selective relationship between E3s and substrates is becoming a hot spot. This article will discuss the recognition mechanism between E3s and substrates, the high throughput methods used for the identification of E3’s substrates, review the bioinformatics study about E3s’ substrates and highlight the future research direction.

Key words: ubiquitination, ubiquitin-ligase, substrate, bioinformatics