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Constance J. Jeffery - One of the best experts on this subject based on the ideXlab platform.
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Multitalented actors inside and outside the cell: recent discoveries add to the number of Moonlighting proteins.
Biochemical Society transactions, 2019Co-Authors: Constance J. JefferyAbstract:During the past few decades, it's become clear that many enzymes evolved not only to act as specific, finely tuned and carefully regulated catalysts, but also to perform a second, completely different function in the cell. In general, these Moonlighting proteins have a single polypeptide chain that performs two or more distinct and physiologically relevant biochemical or biophysical functions. This mini-review describes examples of Moonlighting proteins that have been found within the past few years, including some that play key roles in human and animal diseases and in the regulation of biochemical pathways in food crops. Several belong to two of the most common subclasses of Moonlighting proteins: trigger enzymes and intracellular/surface Moonlighting proteins, but a few represent less often observed combinations of functions. These examples also help illustrate some of the current methods used for identifying proteins with multiple functions. In general, a greater understanding about the functions and molecular mechanisms of Moonlighting proteins, their roles in the regulation of cellular processes, and their involvement in health and disease could aid in many areas including developing new antibiotics, predicting the functions of the millions of proteins being identified through genome sequencing projects, designing novel proteins, using biological circuitry analysis to construct bacterial strains that are better producers of materials for industrial use, and developing methods to tweak biochemical pathways for increasing yields of food crops.
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Moonlighting proteins - nature's Swiss army knives.
Science progress, 2017Co-Authors: Constance J. JefferyAbstract:The human body is a complex biological machine with billions of cells and vast numbers of biochemical processes - but our genome only contains 22,000 protein-encoding genes. Moonlighting proteins provide one way to increase the number of cellular activities. Moonlighting proteins exhibit more than one physiologically relevant biochemical or biophysical function within one polypeptide chain. Already more than 300 Moonlighting proteins have been identified, and they include a diverse set of proteins with a large variety of functions. This article discusses examples of Moonlighting proteins, how one protein structure can perform two different functions, and how the multiple functions can be regulated. In addition to learning more about what our proteins do and how they work together in complex multilayered interaction networks and processes in our bodies, the study of Moonlighting proteins can inform future synthetic biology projects in making proteins that perform new functions and new combinations of functions, for example, for synthesising new materials, delivering drugs into cells, and in bioremediation.
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MoonProt 2.0: An Expansion and Update of the Moonlighting Proteins Database
Nucleic acids research, 2017Co-Authors: Chang Chen, Wangfei Wang, Shadi Zabad, Haipeng Liu, Constance J. JefferyAbstract:MoonProt 2.0 (http://Moonlightingproteins.org) is an updated, comprehensive and open-access database storing expert-curated annotations for Moonlighting proteins. Moonlighting proteins contain two or more physiologically relevant distinct functions performed by a single polypeptide chain. Here, we describe developments in the MoonProt website and database since our previous report in the Database Issue of Nucleic Acids Research. For this V 2.0 release, we expanded the number of proteins annotated to 370 and modified several dozen protein annotations with additional or updated information, including more links to protein structures in the Protein Data Bank, compared with the previous release. The new entries include more examples from humans and several model organisms, more proteins involved in disease, and proteins with different combinations of functions. The updated web interface includes a search function using BLAST to enable users to search the database for proteins that share amino acid sequence similarity with a protein of interest. The updated website also includes additional background information about Moonlighting proteins and an expanded list of links to published articles about Moonlighting proteins.
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Protein species and Moonlighting proteins: Very small changes in a protein's covalent structure can change its biochemical function.
Journal of proteomics, 2015Co-Authors: Constance J. JefferyAbstract:Abstract In the past few decades, hundreds of Moonlighting proteins have been identified that perform two or more distinct and physiologically relevant biochemical or biophysical functions that are not due to gene fusions, multiple RNA splice variants, or pleiotropic effects. For this special issue on protein species, this article discusses three topics related to Moonlighting proteins that illustrate how small changes or differences in protein covalent structures can result in different functions. Examples are given of Moonlighting proteins that switch between functions after undergoing post-translational modifications (PTMs), proteins that share high levels of amino acid sequence identity to a Moonlighting protein but share only one of its functions, and several “neomorphic Moonlighting proteins” in which a single amino acid mutation results in the addition of a new function. Biological significance For this special issue on protein species, this article discusses three topics related to Moonlighting proteins : Post-translational modifications (PTMs) that can cause a switch between functions, homologs that share only one of multiple functions, and proteins in which a single amino acid mutation results in the creation of a new function. The examples included illustrate that even in an average protein of hundreds of amino acids, a relatively small difference in sequence or PTMs can result in a large difference in function, which can be important in predicting protein functions, regulation of protein functions, and in the evolution of new functions.
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Physical Features of Intracellular Proteins that Moonlight on the Cell Surface.
PloS one, 2015Co-Authors: Vaishak Amblee, Constance J. JefferyAbstract:Moonlighting proteins comprise a subset of multifunctional proteins that perform two or more biochemical functions that are not due to gene fusions, multiple splice variants, proteolytic fragments, or promiscuous enzyme activities. The project described herein focuses on a sub-set of Moonlighting proteins that have a canonical biochemical function inside the cell and perform a second biochemical function on the cell surface in at least one species. The goal of this project is to consider the biophysical features of these Moonlighting proteins to determine whether they have shared characteristics or defining features that might suggest why these particular proteins were adopted for a second function on the cell surface, or if these proteins resemble typical intracellular proteins. The latter might suggest that many other normally intracellular proteins found on the cell surface might also be Moonlighting in this fashion. We have identified 30 types of proteins that have different functions inside the cell and on the cell surface. Some of these proteins are found to moonlight on the surface of multiple species, sometimes with different extracellular functions in different species, so there are a total of 98 proteins in the study set. Although a variety of intracellular proteins (enzymes, chaperones, etc.) are observed to be re-used on the cell surface, for the most part, these proteins were found to have physical characteristics typical of intracellular proteins. Many other intracellular proteins have also been found on the surface of bacterial pathogens and other organisms in proteomics experiments. It is quite possible that many of those proteins also have a Moonlighting function on the cell surface. The increasing number and variety of known Moonlighting proteins suggest that there may be more Moonlighting proteins than previously thought, and Moonlighting might be a common feature of many more proteins.
Daisuke Kihara - One of the best experts on this subject based on the ideXlab platform.
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Identification of Moonlighting Proteins in Genomes Using Text Mining Techniques
Proteomics, 2018Co-Authors: Aashish Jain, Hareesh Gali, Daisuke KiharaAbstract:Moonlighting proteins is an emerging concept for considering protein functions, which indicate proteins with two or more independent and distinct functions. An increasing number of Moonlighting proteins have been reported in the past years; however, a systematic study of the topic has been hindered because the secondary functions of proteins are usually found serendipitously by experiments. Toward systematic identification and study of Moonlighting proteins, computational methods for identifying Moonlighting proteins from several different information sources, database entries, literature, and large-scale omics data have been developed. In this study, an overview for finding Moonlighting proteins is discussed. Then, the literature-mining method, DextMP, is applied to find new Moonlighting proteins in three genomes, Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster. Potential Moonlighting proteins identified by DextMP are further examined by a two-step manual literature checking procedure, which finally yielded 13 new Moonlighting proteins. Identified Moonlighting proteins are categorized into two classes based on the clarity of the distinctness of two functions of the proteins. A few cases of the identified Moonlighting proteins are described in detail. Further direction for improving the DextMP algorithm is also discussed.
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MPFit: Computational Tool for Predicting Moonlighting Proteins.
Methods in molecular biology (Clifton N.J.), 2017Co-Authors: Ishita K. Khan, Joshua Mcgraw, Daisuke KiharaAbstract:An increasing number of proteins have been found which are capable of performing two or more distinct functions. These proteins, known as Moonlighting proteins, have drawn much attention recently as they may play critical roles in disease pathways and development. However, because Moonlighting proteins are often found serendipitously, our understanding of Moonlighting proteins is still quite limited. In order to lay the foundation for systematic Moonlighting proteins studies, we developed MPFit, a software package for predicting Moonlighting proteins from their omics features including protein-protein and gene interaction networks. Here, we describe and demonstrate the algorithm of MPFit, the idea behind it, and provide instruction for using the software.
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Genome-scale identification and characterization of Moonlighting proteins
Biology direct, 2014Co-Authors: Ishita K. Khan, Yuqian Chen, Tiange Dong, Xioawei Hong, Rikiya Takeuchi, Hirotada Mori, Daisuke KiharaAbstract:Background: Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify Moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find Moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins. Results: First, we analyzed Gene Ontology (GO) annotations of known Moonlighting proteins. We found that the GO annotations of Moonlighting proteins can be clustered into multiple groups reflecting their diverse functions. Then, by considering the observed GO term separations, we identified 33 novel Moonlighting proteins in Escherichia coli and confirmed them by literature review. Next, we analyzed Moonlighting proteins in terms of protein-protein interaction, gene expression, phylogenetic profile, and genetic interaction networks. We found that Moonlighting proteins physically interact with a higher number of distinct functional classes of proteins than non-Moonlighting ones and also found that most of the physically interacting partners of Moonlighting proteins share the latter’ sp rimary functions. Interestingly, we also found that Moonlighting proteins tend to interact with other Moonlighting proteins. In terms of gene expression and phylogenetically related proteins, a weak trend was observed that Moonlighting proteins interact with more functionally diverse proteins. Structural characteristics of Moonlighting proteins, i.e. intrinsic disordered regions and ligand binding sites were also investigated. Conclusion: Additional functions of Moonlighting proteins are difficult to identify by experiments and these proteins also pose a significant challenge for computational function annotation. Our method enables identification of novel Moonlighting proteins from current functional annotations in public databases. Moreover, we showed that potential Moonlighting proteins without sufficient functional annotations can be identified by analyzing available omics-scale data. Our findings open up new possibilities for investigating the multi-functional nature of proteins at the systems level and for exploring the complex functional interplay of proteins in a cell.
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genome scale identification and characterization of Moonlighting proteins
Biology Direct, 2014Co-Authors: Ishita K. Khan, Yuqian Chen, Tiange Dong, Xioawei Hong, Rikiya Takeuchi, Hirotada Mori, Daisuke KiharaAbstract:Background Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify Moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find Moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins.
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Genome-scale identification and characterization of Moonlighting proteins
Biology Direct, 2014Co-Authors: Ishita Khan, Yuqian Chen, Tiange Dong, Xioawei Hong, Rikiya Takeuchi, Hirotada Mori, Daisuke KiharaAbstract:Background Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify Moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find Moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins. Results First, we analyzed Gene Ontology (GO) annotations of known Moonlighting proteins. We found that the GO annotations of Moonlighting proteins can be clustered into multiple groups reflecting their diverse functions. Then, by considering the observed GO term separations, we identified 33 novel Moonlighting proteins in Escherichia coli and confirmed them by literature review. Next, we analyzed Moonlighting proteins in terms of protein-protein interaction, gene expression, phylogenetic profile, and genetic interaction networks. We found that Moonlighting proteins physically interact with a higher number of distinct functional classes of proteins than non-Moonlighting ones and also found that most of the physically interacting partners of Moonlighting proteins share the latter’s primary functions. Interestingly, we also found that Moonlighting proteins tend to interact with other Moonlighting proteins. In terms of gene expression and phylogenetically related proteins, a weak trend was observed that Moonlighting proteins interact with more functionally diverse proteins. Structural characteristics of Moonlighting proteins, i.e. intrinsic disordered regions and ligand binding sites were also investigated. Conclusion Additional functions of Moonlighting proteins are difficult to identify by experiments and these proteins also pose a significant challenge for computational function annotation. Our method enables identification of novel Moonlighting proteins from current functional annotations in public databases. Moreover, we showed that potential Moonlighting proteins without sufficient functional annotations can be identified by analyzing available omics-scale data. Our findings open up new possibilities for investigating the multi-functional nature of proteins at the systems level and for exploring the complex functional interplay of proteins in a cell. Reviewers This article was reviewed by Michael Galperin, Eugine Koonin, and Nick Grishin.
Christine Brun - One of the best experts on this subject based on the ideXlab platform.
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Understanding protein multifunctionality: from short linear motifs to cellular functions
Cellular and Molecular Life Sciences, 2019Co-Authors: Andreas Zanzoni, Diogo M Ribeiro, Christine BrunAbstract:Moonlighting proteins perform multiple unrelated functions without any change in polypeptide sequence. They can coordinate cellular activities, serving as switches between pathways and helping to respond to changes in the cellular environment. Therefore, regulation of the multiple protein activities, in space and time, is likely to be important for the homeostasis of biological systems. Some Moonlighting proteins may perform their multiple functions simultaneously while others alternate between functions due to certain triggers. The switch of the Moonlighting protein’s functions can be regulated by several distinct factors, including the binding of other molecules such as proteins. We here review the approaches used to identify Moonlighting proteins and existing repositories. We particularly emphasise the role played by short linear motifs and PTMs as regulatory switches of Moonlighting functions.
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Relationships between predicted Moonlighting proteins, human diseases, and comorbidities from a network perspective
Frontiers in Physiology, 2015Co-Authors: Andreas Zanzoni, Charles E. Chapple, Christine BrunAbstract:Moonlighting proteins are a subset of multifunctional proteins characterized by their multiple, independent, and unrelated biological functions. We recently set up a large-scale identification of Moonlighting proteins using a protein-protein interaction (PPI) network approach. We established that 3% of the current human interactome is composed of predicted Moonlighting proteins. We found that disease-related genes are over-represented among those candidates. Here, by comparing Moonlighting candidates to non-candidates as groups, we further show that (7 they are significantly involved in more than one disease, (ii) they contribute to complex rather than monogenic diseases, (iii) the diseases in which they are involved are phenotypically different according to their annotations, finally, (iv) they are enriched for diseases pairs showing statistically significant comorbidity patterns based on Medicare records. Altogether, our results suggest that some observed comorbidities between phenotypically different diseases could be due to a shared protein involved in unrelated biological processes.
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Extreme multifunctional proteins identified from a human protein interaction network
Nature Communications, 2015Co-Authors: Charles E. Chapple, Benoit Robisson, Lionel Spinelli, Céline Guien, Emmanuelle Becker, Christine BrunAbstract:Proteins are sometimes implicated in separate and seemingly unrelated processes, so called Moonlighting functions. Here the authors use bioinformatics tools to identify extreme multifunctional proteins and define a signature of extreme multifunctionality. Moonlighting proteins are a subclass of multifunctional proteins whose functions are unrelated. Although they may play important roles in cells, there has been no large-scale method to identify them, nor any effort to characterize them as a group. Here, we propose the first method for the identification of ‘extreme multifunctional’ proteins from an interactome as a first step to characterize Moonlighting proteins. By combining network topological information with protein annotations, we identify 430 extreme multifunctional proteins (3% of the human interactome). We show that the candidates form a distinct sub-group of proteins, characterized by specific features, which form a signature of extreme multifunctionality. Overall, extreme multifunctional proteins are enriched in linear motifs and less intrinsically disordered than network hubs. We also provide MoonDB, a database containing information on all the candidates identified in the analysis and a set of manually curated human Moonlighting proteins.
Enrique Querol - One of the best experts on this subject based on the ideXlab platform.
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A hypothesis explaining why so many pathogen virulence proteins are Moonlighting proteins.
Pathogens and disease, 2018Co-Authors: Luis Franco-serrano, Isaac Amela, Jaume Piñol, Juan Cedano, Josepantoni Perez-pons, Angel Mozo-villarias, Enrique QuerolAbstract:Moonlighting or multitasking proteins refer to those proteins with two or more functions performed by a single polypeptide chain. Proteins that belong to key ancestral functions and metabolic pathways such as primary metabolism typically exhibit Moonlighting phenomenon. We have collected 698 Moonlighting proteins in MultitaskProtDB-II database. A survey shows that 25% of the proteins of the database correspond to Moonlighting functions related to pathogens virulence activity. Why is the canonical function of these virulence proteins mainly from ancestral key biological functions (especially of primary metabolism)? Our hypothesis is that these proteins present a high conservation between the pathogen protein and the host counterparts. Therefore, the host immune system will not elicit protective antibodies against pathogen proteins. The fact of sharing epitopes with host proteins (known as epitope mimicry) might be the cause of autoimmune diseases. Although many pathogen proteins can be antigenic, only a few of them would elicit a protective immune response. This would also explain the lack of successful vaccines based in these conserved Moonlighting proteins. This review looks at why so many pathogen virulence proteins are from the primary metabolism and are conserved between pathogen and host.
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Do Moonlighting Proteins Belong to the Intrinsically Disordered Protein Class
Journal of Proteomics & Bioinformatics, 2012Co-Authors: Sergio Hernández, Isaac Amela, Jaume Piñol, Juan Cedano, Josepantoni Perez-pons, Angel Mozo-villarias, Enrique QuerolAbstract:Moonlighting is the capability of some proteins to execute two or more biological functions. According to some authors, there is a relationship between protein conformational fluctuations and promiscuous functions of proteins. This promiscuity would be due to the conformational properties of the structurally disordered regions. To check if Moonlighting proteins belong to the Intrinsically Disordered Protein (IDP) class, we have predicted IDP/IDR (Intrinsically Disordered Regions) for a number of Moonlighting proteins. Our results suggest that most Moonlighting proteins do not belong to the IDP class.
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do protein protein interaction databases identify Moonlighting proteins
Molecular BioSystems, 2011Co-Authors: Antonio Castillo Gómez, Sergio Hernández, Isaac Amela, Jaume Piñol, Juan Cedano, Enrique QuerolAbstract:One of the most striking results of the human (and mammalian) genomes is the low number of protein-coding genes. To-date, the main molecular mechanism to increase the number of different protein isoforms and functions is alternative splicing. However, a less-known way to increase the number of protein functions is the existence of multifunctional, multitask, or “Moonlighting”, proteins. By and large, Moonlighting proteins are experimentally disclosed by serendipity. Proteomics is becoming one of the very active areas of biomedical research, which permits researchers to identify previously unseen connections among proteins and pathways. In principle, protein–protein interaction (PPI) databases should contain information on Moonlighting proteins and could provide suggestions to further analysis in order to prove the multifunctionality. As far as we know, nobody has verified whether PPI databases actually disclose Moonlighting proteins. In the present work we check whether well-established Moonlighting proteins present in PPI databases connect with their known partners and, therefore, a careful inspection of these databases could help to suggest their different functions. The results of our research suggest that PPI databases could be a valuable tool to suggest multifunctionality.
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Do protein–protein interaction databases identify Moonlighting proteins?
Molecular bioSystems, 2011Co-Authors: Antonio Castillo Gómez, Sergio Hernández, Isaac Amela, Jaume Piñol, Juan Cedano, Enrique QuerolAbstract:One of the most striking results of the human (and mammalian) genomes is the low number of protein-coding genes. To-date, the main molecular mechanism to increase the number of different protein isoforms and functions is alternative splicing. However, a less-known way to increase the number of protein functions is the existence of multifunctional, multitask, or “Moonlighting”, proteins. By and large, Moonlighting proteins are experimentally disclosed by serendipity. Proteomics is becoming one of the very active areas of biomedical research, which permits researchers to identify previously unseen connections among proteins and pathways. In principle, protein–protein interaction (PPI) databases should contain information on Moonlighting proteins and could provide suggestions to further analysis in order to prove the multifunctionality. As far as we know, nobody has verified whether PPI databases actually disclose Moonlighting proteins. In the present work we check whether well-established Moonlighting proteins present in PPI databases connect with their known partners and, therefore, a careful inspection of these databases could help to suggest their different functions. The results of our research suggest that PPI databases could be a valuable tool to suggest multifunctionality.
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Do current sequence analysis algorithms disclose multifunctional (Moonlighting) proteins
Bioinformatics (Oxford England), 2003Co-Authors: Antonio Castillo Gómez, Jaume Piñol, Juan Cedano, Nuria Domedel, Enrique QuerolAbstract:Summary: An umber of multifunctional, ‘Moonlighting’, proteins have been analyzed by different current programs to test wheter they identify both functions. PSI-BLAST and PRODOM perform best in predicting the alternative function. Contact: enric.querol@uab.es Supplementary information: Full tables and additional information available at http://ibb.uab.es/Moonlighting
Isaac Amela - One of the best experts on this subject based on the ideXlab platform.
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A hypothesis explaining why so many pathogen virulence proteins are Moonlighting proteins.
Pathogens and disease, 2018Co-Authors: Luis Franco-serrano, Isaac Amela, Jaume Piñol, Juan Cedano, Josepantoni Perez-pons, Angel Mozo-villarias, Enrique QuerolAbstract:Moonlighting or multitasking proteins refer to those proteins with two or more functions performed by a single polypeptide chain. Proteins that belong to key ancestral functions and metabolic pathways such as primary metabolism typically exhibit Moonlighting phenomenon. We have collected 698 Moonlighting proteins in MultitaskProtDB-II database. A survey shows that 25% of the proteins of the database correspond to Moonlighting functions related to pathogens virulence activity. Why is the canonical function of these virulence proteins mainly from ancestral key biological functions (especially of primary metabolism)? Our hypothesis is that these proteins present a high conservation between the pathogen protein and the host counterparts. Therefore, the host immune system will not elicit protective antibodies against pathogen proteins. The fact of sharing epitopes with host proteins (known as epitope mimicry) might be the cause of autoimmune diseases. Although many pathogen proteins can be antigenic, only a few of them would elicit a protective immune response. This would also explain the lack of successful vaccines based in these conserved Moonlighting proteins. This review looks at why so many pathogen virulence proteins are from the primary metabolism and are conserved between pathogen and host.
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multitaskprotdb ii an update of a database of multitasking Moonlighting proteins
Nucleic Acids Research, 2018Co-Authors: Luis Francoserrano, Sergio Hernández, Jaume Piñol, Alejandra Calvo, María A Severi, Gabriela Ferragut, Oscar Q. Pich, Josepantoni Perezpons, Angel Mozovillarias, Isaac AmelaAbstract:Multitasking, or Moonlighting, is the capability of some proteins to execute two or more biological functions. MultitaskProtDB-II is a database of multifunctional proteins that has been updated. In the previous version, the information contained was: NCBI and UniProt accession numbers, canonical and additional biological functions, organism, monomeric/oligomeric states, PDB codes and bibliographic references. In the present update, the number of entries has been increased from 288 to 694 Moonlighting proteins. MultitaskProtDB-II is continually being curated and updated. The new database also contains the following information: GO descriptors for the canonical and Moonlighting functions, three-dimensional structure (for those proteins lacking PDB structure, a model was made using Itasser and Phyre), the involvement of the proteins in human diseases (78% of human Moonlighting proteins) and whether the protein is a target of a current drug (48% of human Moonlighting proteins). These numbers highlight the importance of these proteins for the analysis and explanation of human diseases and target-directed drug design. Moreover, 25% of the proteins of the database are involved in virulence of pathogenic microorganisms, largely in the mechanism of adhesion to the host. This highlights their importance for the mechanism of microorganism infection and vaccine design. MultitaskProtDB-II is available at http://wallace.uab.es/multitaskII.
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MultitaskProtDB-II: an update of a database of multitasking/Moonlighting proteins.
Nucleic acids research, 2017Co-Authors: Luis Franco-serrano, Sergio Hernández, Jaume Piñol, Josepantoni Perez-pons, Angel Mozo-villarias, Alejandra Calvo, María A Severi, Gabriela Ferragut, Oscar Q. Pich, Isaac AmelaAbstract:Multitasking, or Moonlighting, is the capability of some proteins to execute two or more biological functions. MultitaskProtDB-II is a database of multifunctional proteins that has been updated. In the previous version, the information contained was: NCBI and UniProt accession numbers, canonical and additional biological functions, organism, monomeric/oligomeric states, PDB codes and bibliographic references. In the present update, the number of entries has been increased from 288 to 694 Moonlighting proteins. MultitaskProtDB-II is continually being curated and updated. The new database also contains the following information: GO descriptors for the canonical and Moonlighting functions, three-dimensional structure (for those proteins lacking PDB structure, a model was made using Itasser and Phyre), the involvement of the proteins in human diseases (78% of human Moonlighting proteins) and whether the protein is a target of a current drug (48% of human Moonlighting proteins). These numbers highlight the importance of these proteins for the analysis and explanation of human diseases and target-directed drug design. Moreover, 25% of the proteins of the database are involved in virulence of pathogenic microorganisms, largely in the mechanism of adhesion to the host. This highlights their importance for the mechanism of microorganism infection and vaccine design. MultitaskProtDB-II is available at http://wallace.uab.es/multitaskII.
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Do Moonlighting Proteins Belong to the Intrinsically Disordered Protein Class
Journal of Proteomics & Bioinformatics, 2012Co-Authors: Sergio Hernández, Isaac Amela, Jaume Piñol, Juan Cedano, Josepantoni Perez-pons, Angel Mozo-villarias, Enrique QuerolAbstract:Moonlighting is the capability of some proteins to execute two or more biological functions. According to some authors, there is a relationship between protein conformational fluctuations and promiscuous functions of proteins. This promiscuity would be due to the conformational properties of the structurally disordered regions. To check if Moonlighting proteins belong to the Intrinsically Disordered Protein (IDP) class, we have predicted IDP/IDR (Intrinsically Disordered Regions) for a number of Moonlighting proteins. Our results suggest that most Moonlighting proteins do not belong to the IDP class.
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do protein protein interaction databases identify Moonlighting proteins
Molecular BioSystems, 2011Co-Authors: Antonio Castillo Gómez, Sergio Hernández, Isaac Amela, Jaume Piñol, Juan Cedano, Enrique QuerolAbstract:One of the most striking results of the human (and mammalian) genomes is the low number of protein-coding genes. To-date, the main molecular mechanism to increase the number of different protein isoforms and functions is alternative splicing. However, a less-known way to increase the number of protein functions is the existence of multifunctional, multitask, or “Moonlighting”, proteins. By and large, Moonlighting proteins are experimentally disclosed by serendipity. Proteomics is becoming one of the very active areas of biomedical research, which permits researchers to identify previously unseen connections among proteins and pathways. In principle, protein–protein interaction (PPI) databases should contain information on Moonlighting proteins and could provide suggestions to further analysis in order to prove the multifunctionality. As far as we know, nobody has verified whether PPI databases actually disclose Moonlighting proteins. In the present work we check whether well-established Moonlighting proteins present in PPI databases connect with their known partners and, therefore, a careful inspection of these databases could help to suggest their different functions. The results of our research suggest that PPI databases could be a valuable tool to suggest multifunctionality.