Abstract

Ubiquitin (Ub) is a small protein that consists of 76 amino acids about 8.5 kDa. In ubiquitin conjugation, the ubiquitin is majorly conjugated on the lysine residue of protein by Ub-ligating (E3) enzymes. Three major enzymes participate in ubiquitin conjugation. They are – E1, E2 and E3 which are responsible for activating, conjugating and ligating ubiquitin, respectively. Ubiquitin conjugation in eukaryotes is an important mechanism of the proteasome-mediated degradation of a protein and regulating the activity of transcription factors. Motivated by the importance of ubiquitin conjugation in biological processes, this investigation develops a method, UbSite, which uses utilizes an efficient radial basis function (RBF) network to identify protein ubiquitin conjugation (ubiquitylation) sites. This work not only investigates the amino acid composition but also the structural characteristics, physicochemical properties, and evolutionary information of amino acids around ubiquitylation (Ub) sites. With reference to the pathway of ubiquitin conjugation, the substrate sites for E3 recognition, which are distant from ubiquitylation sites, are investigated. The measurement of F-score in a large window size (−20∼+20) revealed a statistically significant amino acid composition and position-specific scoring matrix (evolutionary information), which are mainly located distant from Ub sites. The distant information can be used effectively to differentiate Ub sites from non-Ub sites. As determined by five-fold cross-validation, the model that was trained using the combination of amino acid composition and evolutionary information performs best in identifying ubiquitin conjugation sites. The prediction sensitivity, specificity, and accuracy are 65.5%, 74.8%, and 74.5%, respectively. Although the amino acid sequences around the ubiquitin conjugation sites do not contain conserved motifs, the cross-validation result indicates that the integration of distant sequence features of Ub sites can improve predictive performance. Additionally, the independent test demonstrates that the proposed method can outperform other ubiquitylation prediction tools.

Highlights

  • Ubiquitin (Ub) is a small protein that consists of 76 amino acids about 8.5 kDa

  • Amino acid composition of ubiquitin conjugation sites This investigation focuses on the analysis of ubiquitin conjugated lysine

  • After the duplicated sequences of experimental ubiquitylation sites are removed, as shown in Fig. 3, the amino acids composition that flanked the ubiquitin-conjugated lysines are graphically visualized as a 41-mer sequence logo

Read more

Summary

Introduction

Ubiquitin (Ub) is a small protein that consists of 76 amino acids about 8.5 kDa. Ubiquitin conjugation sites of protein (Ubiquitylation), which is an essential post-translational modification, is a sequential process that involves a group of enzymes known as E1 (activating enzyme), E2 (conjugating enzyme) and E3 (ubiquitin ligase). The ubiquitylation system is well-known for the selective degradation of serveral short-lived proteins in eukaryotic cells [1]. The attachment of a ubiquitin or poly-ubiquitin chains to proteins influences serveral cellular processes, including transcriptional regulation, signal transduction, development, apoptosis, endocytosis, and cell proliferation [2]. The E3 ligase must be sufficiently specific and must act only on a defined subset of cellular targets to ensure signal fidelity [3]. Another enzyme, E4, has that can stabilize and extend a poly-ubiquitin chain, has been found [4]

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call