Differential Use of Signal Peptides and Membrane Domains Is a Common Occurrence in the Protein Output of Transcriptional Units

Davis, Melissa J.; Hanson, Kelly; Clark, Francis; Fink, J. Lynn; Zhang, Fasheng; Kasukawa, Takeya; Cui, Kai; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Teasdale, Rohan D.

doi:10.1371/journal.pgen.0020046

Cited by 38 publications

(38 citation statements)

References 54 publications

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“…This number is in accordance with other similar estimates for human and mouse (3,6). The chromosomal distribution of the surfaceome set resembled the distribution of human genes in general except for a higher density on chromosome 11, due to a large cluster of olfactory receptors that map to this chromosome (Table S1).…”

Section: Resultssupporting

confidence: 90%

Bioinformatics construction of the human cell surfaceome

Cunha

Galante

Souza

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

125

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Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.colorectal tumors ͉ CT antigens ͉ glioblastoma ͉ transmembrane ͉ tumor cell surface antigens W ith the availability of the human genome sequence, an important goal of current biological research is a more specific and accurate annotation of human genes. One critical property is the subcellular localization of gene products, because this affects their use as potential diagnostic and therapeutic targets. In this respect, the identification of cell surface proteins is of particular interest (1-3) because these proteins represent ideal therapeutic targets. Indeed, cell surface proteins have proved to be relevant to many areas of medicine, and a number of monoclonal antibodies against them are approved for therapeutic applications by the Food and Drug Administration, particularly in cancer therapy. Furthermore, cell surface proteins are also excellent targets for diagnostic assays, especially in biological fluids. On the other hand, there are several issues that make cell surface proteins difficult to manipulate biochemically. First, their hydrophobic transmembrane (TM) domain makes them insoluble. Second, several posttranslational modifications are not executed in commonly used expression systems. Finally, interactions involving cell surface proteins usually have an extremely short half-life (on the order of milliseconds), which has an effect on the development of purification protocols. Despite these limitations, decades of intensive research of cell surface proteins have generated a significant information base. Ideally, this information should be analyzed in a genome-wide context.We generated here a catalog of more than 3,700 genes believed to encode proteins located at the surface of human cells. For the sake of simplicity, we will call this catalog the ''human cell surfaceome.'' An integrated ...

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Section: Resultssupporting

confidence: 90%

Bioinformatics construction of the human cell surfaceome

Cunha

Galante

Souza

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

125

View full text Add to dashboard Cite

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“…For the comparison of protein subcellular localization, we compared gene pairs only if HMM and NN methods resulted in the same signal peptide prediction. We defined subcellular localization by five categories, following the classification of Davis et al (2006a): (1) …”

Section: Protein Domain Architecture and Subcellular Localizationmentioning

confidence: 99%

Evolution of gene function and regulatory control after whole-genome duplication: Comparative analyses in vertebrates

et al. 2009

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The significance of whole-genome duplications (WGD) for vertebrate evolution remains controversial, in part because the mechanisms by which WGD contributed to functional evolution or speciation are still incompletely characterized. Fish genomes provide an ideal context in which to examine the consequences of WGD, because the teleost lineage experienced an additional WGD soon after divergence from tetrapods and because five teleost genomes are available for comparative analysis. Here we present an integrated approach to characterize these post-duplication genomes based on genome-scale synteny, phylogenetic, temporal, and spatial gene expression and on protein sequence data. A minimum of 3%-4% of protein-coding loci have been retained in two copies in each of the five fish genomes, and many of these duplicates are key developmental genes that function as transcription factors or signaling molecules. Almost all duplicate gene pairs we examined have diverged in spatial and/or temporal expression during embryogenesis. A quarter of duplicate pairs have diverged in function via the acquisition of novel protein domains or via changes in the subcellular localization of their encoded proteins. We compared the spatial expression and protein domain architecture of zebrafish WGD-duplicates to those of their single mouse ortholog and found many examples supporting a model of neofunctionalization. WGDduplicates have acquired novel protein domains more often than have single-copy genes. Post-WGD changes at the gene regulatory level were more common than changes at the protein level. We conclude that the most significant consequence of WGD for vertebrate evolution has been to enable more-specialized regulatory control of development via the acquisition of novel spatiotemporal expression domains. We find limited evidence that reciprocal gene loss led to reproductive isolation and speciation in this lineage.

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“…Sequence analysis revealed no potential transmembrane domain or signal peptide in UL2, indicating that it might be neither a transmembrane protein nor a secretory protein (Davis et al, 2006). However, a potential N-linked glycosylation site (Asn-Thr-Thr-Leu) located at aa 218 was present in UL2 (see Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of the pseudorabies virus UL2 gene

Cai

Wang²,

Cui³

et al. 2013

Genet. Mol. Res.

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ABSTRACT.A 948-bp sequence of the UL2 gene was amplified from the pseudorabies virus (PRV) Becker strain genome using polymerase chain reaction, and the gene identity was confirmed through further cloning and sequencing. Bioinformatic analysis indicated that the PRV UL2 gene encodes a putative polypeptide with 315-amino acid residues. Its encoding protein, designated UL2, has a conserved uracil-DNA glycosylase (UDG)_F1 domain, which is closely related to the herpesvirus UDG family and is highly conserved among its counterparts encoded by UDG genes. Multiple nucleic acid and amino acid sequence alignments suggested that the product of PRV UL2 has a relatively higher homology with UL2-like proteins of Alphaherpesvirinae than that of other subfamilies of Herpesviridae. In addition, phylogenetic analysis showed that PRV UL2 had a close evolutionary relationship with members of Alphaherpesvirinae, especially members of the genus Varicellovirus of bovine herpesvirus 1 and bovine herpesvirus 5. Antigen prediction indicated the presence of several potential B-cell epitopes in PRV UL2. In addition, secondary structure and 3-dimensional structure prediction revealed that PRV UL2 consisted predominantly of an α-helix. Taken together, these results provide molecular biological insight for the further study of the function and mechanism of UL2 during PRV infection.

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Differential Use of Signal Peptides and Membrane Domains Is a Common Occurrence in the Protein Output of Transcriptional Units

Cited by 38 publications

References 54 publications

Bioinformatics construction of the human cell surfaceome

Bioinformatics construction of the human cell surfaceome

Evolution of gene function and regulatory control after whole-genome duplication: Comparative analyses in vertebrates

Molecular characterization of the pseudorabies virus UL2 gene

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