Estimation of Membrane Proteins in the Human Proteome

Article type: Research Article

Authors: Ahram, Mamoun | Litou, Zoi I. | Fang, Ruihua | Al-Tawallbeh, Ghaith

Affiliations: Department of Pharmacology and Physiology, Faculty of Medicine, Mutah University, Mutah Karak 61710, Jordan | Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece | Computational Proteomics Laboratory, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

Note: [] Corresponding author. Tel.: +962 3 238 6287; Fax: +962 3 238 6175; E-mail: [email protected]

Abstract: Genomics and proteomics have added valuable information to our knowledgebase of the human biological system including the discovery of therapeutic targets and disease biomarkers. However, molecular profiling studies commonly result in the identification of novel proteins of unknown localization. A class of proteins of special interest is membrane proteins, in particular plasma membrane proteins. Despite their biological and medical significance, the 3-dimensional structures of less than 1% of plasma membrane proteins have been determined. In order to aid in identification of membrane proteins, a number of computational methods have been developed. These tools operate by predicting the presence of transmembrane segments. Here, we utilized five topology prediction methods (TMHMM, SOSUI, waveTM, HMMTOP, and TopPred II) in order to estimate the ratio of integral membrane proteins in the human proteome. These methods employ different algorithms and include a newly-developed method (waveTM) that has yet to be tested on a large proteome database. Since these tools are prone for error mainly as a result of falsely predicting signal peptides as transmembrane segments, we have utilized an additional method, SignalP. Based on our analyses, the ratio of human proteins with transmembrane segments is estimated to fall between 15% and 39% with a consensus of 13%. Agreement among the programs is reduced further when both a positive identification of a membrane protein and the number of transmembrane segments per protein are considered. Such a broad range of prediction depends on the selectivity of the individual method in predicting integral membrane proteins. These methods can play a critical role in determining protein structure and, hence, identifying suitable drug targets in humans.

Keywords: Membrane proteins, human, proteome, transmembrane segment, bioinformatics, prediction, proteomics, waveTM, TMHMM, HMMTOP, SOSUI, TopPred II, SignalP

Journal: In Silico Biology, vol. 6, no. 5, pp. 379-386, 2006