Abstract

BackgroundMembrane proteins perform essential roles in diverse cellular functions and are regarded as major pharmaceutical targets. The significance of membrane proteins has led to the developing dozens of resources related with membrane proteins. However, most of these resources are built for specific well-known membrane protein groups, making it difficult to find common and specific features of various membrane protein groups.MethodsWe collected human membrane proteins from the dispersed resources and predicted novel membrane protein candidates by using ortholog information and our membrane protein classifiers. The membrane proteins were classified according to the type of interaction with the membrane, subcellular localization, and molecular function. We also made new feature dataset to characterize the membrane proteins in various aspects including membrane protein topology, domain, biological process, disease, and drug. Moreover, protein structure and ICD-10-CM based integrated disease and drug information was newly included. To analyze the comprehensive information of membrane proteins, we implemented analysis tools to identify novel sequence and functional features of the classified membrane protein groups and to extract features from protein sequences.ResultsWe constructed HMPAS with 28,509 collected known membrane proteins and 8,076 newly predicted candidates. This system provides integrated information of human membrane proteins individually and in groups organized by 45 subcellular locations and 1,401 molecular functions. As a case study, we identified associations between the membrane proteins and diseases and present that membrane proteins are promising targets for diseases related with nervous system and circulatory system. A web-based interface of this system was constructed to facilitate researchers not only to retrieve organized information of individual proteins but also to use the tools to analyze the membrane proteins.ConclusionsHMPAS provides comprehensive information about human membrane proteins including specific features of certain membrane protein groups. In this system, user can acquire the information of individual proteins and specified groups focused on their conserved sequence features, involved cellular processes, and diseases. HMPAS may contribute as a valuable resource for the inference of novel cellular mechanisms and pharmaceutical targets associated with the human membrane proteins. HMPAS is freely available at http://fcode.kaist.ac.kr/hmpas.

Highlights

  • Membrane proteins perform essential roles in diverse cellular functions and are regarded as major pharmaceutical targets

  • A total of 7,731 novel membrane protein candidates were predicted by using the 3 distinct membrane protein classifiers, which considered their type of interaction with the membrane

  • Pharmaceutical features of membrane proteins Membrane proteins are considered as major pharmaceutical targets

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Summary

Introduction

Membrane proteins perform essential roles in diverse cellular functions and are regarded as major pharmaceutical targets. Membrane protein structure databases can be another source to retrieve membrane proteins [10], but they only contain a limited number of proteins that have experimentally validated structure information This absence of comprehensive membrane protein database, which covers entire membrane proteins with their functional classification information, prevents the identification of both the common and specific characteristics of diverse membrane protein groups. This identification can be critical knowledge to predict novel proteins for a specific membrane protein family, to understand their mechanism of action, and to estimate novel uses of these proteins as drug targets

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