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Human Proteome (human + proteome)
Selected AbstractsSingle amino acid repeats in signal peptidesFEBS JOURNAL, Issue 15 2010abaj There has been an increasing interest in single amino acid repeats ever since it was shown that these are the cause of a variety of diseases. Although a systematic study of single amino acid repeats is challenging, they have subsequently been implicated in a number of functional roles. In general surveys, leucine runs were among the most frequent. In the present study, we present a detailed investigation of repeats in signal peptides of secreted and type I membrane proteins in comparison with their mature parts. We focus on eukaryotic species because single amino acid repeats are generally rather rare in archaea and bacteria. Our analysis of over 100 species shows that repeats of leucine (but not of other hydrophobic amino acids) are over-represented in signal peptides. This trend is most pronounced in higher eukaryotes, particularly in mammals. In the human proteome, although less than one-fifth of all proteins have a signal peptide, approximately two-thirds of all leucine repeats are located in these transient regions. Signal peptides are cleaved early from the growing polypeptide chain and then degraded rapidly. This may explain why leucine repeats, which can be toxic, are tolerated at such high frequencies. The substantial fraction of proteins affected by the strong enrichment of repeats in these transient segments highlights the bias that they can introduce for systematic analyses of protein sequences. In contrast to a general lack of conservation of single amino acid repeats, leucine repeats were found to be more conserved than the remaining signal peptide regions, indicating that they may have an as yet unknown functional role. [source] Monoclonal and polyclonal humoral immune response to EC HER-2/NEU peptides with low similarity to the host's proteomeINTERNATIONAL JOURNAL OF CANCER, Issue 5 2002Abraham Mittelman Abstract We are studying peptide immunogenicity as a function of the similarity level to the host's proteome. By using as a model the breast/prostate cancer-associated HER-2/neu antigen, we analyzed the monoclonal and polyclonal humoral immune responses against HER-2/neu peptide motifs not shared with the host proteome. We show here that (i) a mouse monoclonal antibody (MAb) raised against the extracellular domain (EC) of human HER-2/neu oncoprotein recognized a linear peptide motif endowed with low similarity level to the mouse proteome; (ii) likewise, human sera from breast/prostate cancer patients preferentially recognized peptide fragments from the EC of the HER-2/neu oncoprotein having sequences that are not present in the human proteome. Together with previous results obtained in other disease models (cervical cancer-associated HPV16 E7 oncoprotein and Pemphigus vulgaris auto-antigen desmoglein-3), the present data suggest that a low level of sequence similarity to the host's proteome might be an important factor in shaping the pool of B cell epitopes. © 2002 Wiley-Liss, Inc. [source] A network analysis of the single nucleotide polymorphisms in acute allergic diseasesALLERGY, Issue 1 2010J. Renkonen Abstract Background:, Genetics of acute allergies has focused on identifying single nucleotide polymorphisms (SNPs) within genes relevant in the pathogenesis. In this study, we begin a systems biology analysis of the interconnectivity and biological functions of these genes, their transcripts and their corresponding proteins. Methods:, The literature (Pubmed) was searched for SNPs within genes relevant in acute allergic diseases. The SNP-modified genes were converted to corresponding proteins and their protein,protein interactions were searched from six different databases. This interaction network was analysed with annotated vocabularies (ontologies), such as Gene Ontology, Reactome and Nature pathway interaction database. Time-series transcriptomics was performed with nasal epithelial cells obtained from allergic patients and their healthy control subjects. Results:, A total of 39 genes with SNPs related to acute allergic diseases were found from a literature search. The corresponding proteins were then hooked into a large protein,protein interaction network with the help of various databases. Twenty-five SNP-related proteins had more than one interacting protein and a network contained 95 proteins, and 182 connections could be generated. This network was 10-fold enriched with protein kinases and proteins involved in the host,virus interaction compared with background human proteome. Finally, eight of the 95 nodes on our network displayed nasal epithelial transcriptomal regulation in a time-series analysis collected from birch allergic patients during the spring pollen season. Conclusions:, Signal transduction with special reference to host,virus interactions dominated in the allergy-related protein interaction network. Systems level analysis of allergy-related mutation can provide new insights into pathogenetic mechanisms of the diseases. [source] The epitope space of the human proteomePROTEIN SCIENCE, Issue 4 2008Lisa Berglund Abstract In the post-genome era, there is a great need for protein-specific affinity reagents to explore the human proteome. Antibodies are suitable as reagents, but generation of antibodies with low cross-reactivity to other human proteins requires careful selection of antigens. Here we show the results from a proteome-wide effort to map linear epitopes based on uniqueness relative to the entire human proteome. The analysis was based on a sliding window sequence similarity search using short windows (8, 10, and 12 amino acid residues). A comparison of exact string matching (Hamming distance) and a heuristic method (BLAST) was performed, showing that the heuristic method combined with a grid strategy allows for whole proteome analysis with high accuracy and feasible run times. The analysis shows that it is possible to find unique antigens for a majority of the human proteins, with relatively strict rules involving low sequence identity of the possible linear epitopes. The implications for human antibody-based proteomics efforts are discussed. [source] Is a gene-centric human proteome project the best way for proteomics to serve biology?PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2010Thierry Rabilloud Abstract With the recent developments in proteomic technologies, a complete human proteome project (HPP) appears feasible for the first time. However, there is still debate as to how it should be designed and what it should encompass. In "proteomics speak", the debate revolves around the central question as to whether a gene-centric or a protein-centric proteomics approach is the most appropriate way forward. In this paper, we try to shed light on what these definitions mean, how large-scale proteomics such as a HPP can insert into the larger omics chorus, and what we can reasonably expect from a HPP in the way it has been proposed so far. [source] Affinity reagent resources for human proteome detection: Initiatives and perspectivesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 16 2007Oda Stoevesandt Abstract Essential to the ambition of characterising fully the human proteome are systematic and comprehensive collections of specific affinity reagents directed against all human proteins, including splice variants and modifications. Although a large number of affinity reagents are available commercially, their quality is often questionable and only a fraction of the proteome is covered. In order for more targets to be examined, there is a need for broad availability of panels of affinity reagents, including binders against proteins of unknown functions. The most familiar affinity reagents are antibodies and their fragments, but engineered forms of protein scaffolds and nucleic acid aptamers with similar diversity and binding properties are becoming viable alternatives. Recent initiatives in Europe and the USA have been established to improve both the availability and quality of reagents for affinity proteomics, with the ultimate aim of creating standardised collections of well-validated binding molecules for proteome analysis. As well as coordinating affinity reagent production through existing resources and technology providers, these projects aim to benchmark key molecular entities, tools, and applications, and establish the bioinformatics framework and databases needed. The benefits of such reagent resources will be seen in basic research, medicine and the biotechnology and pharmaceutical industries. [source] | |||||||||||||