Bioinformatics Advance Access originally published online on October 10, 2005
Bioinformatics 2005 21(23):4312-4314; doi:10.1093/bioinformatics/bti704
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ATID: a web-oriented database for collection of publicly available alternative translational initiation events
MOE Key Laboratory of Bioinformatics and Department of Automation, Tsinghua University Beijing 100084, China
*To whom correspondence should be addressed.
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ABSTRACT |
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Summary: Alternative translational initiation is an important cellular mechanism contributing to the diversity of protein products and functions. We develop a database that provides a comprehensive collection of alternative translational initiation events. The purpose of this alternative translational initiation database (ATID) is to facilitate the systematic study of alternative translational initiation of genes. The current version of database contains 300 genes from Homo sapiens, Mus musculus and other species. Each of the genes has two or more isoforms due to alternative translational initiation. Resources in ATID, including gene information, alternative products of genes and domain structures of isoforms, are provided through a user-friendly web interface.
Availability: The ATID database is available for public use at http://bioinfo.au.tsinghua.edu.cn/atie/
Contact: caijun99{at}mails.tsinghua.edu.cn
Supplementary information: Supplementary instructions about this database and further statistical analyses can be found on the web page (http://bioinfo.au.tsinghua.edu.cn/atie/)
The mechanisms to generate protein diversity by alternative gene expression allow an organism to increase its level of complexity. These mechanisms include alternative use of promoters, splice sites and translational initiation codons. Specifically, the use of alternative translational initiation codons in a single mRNA contributes to the generation of protein diversity. The genes produce two or more versions of the proteins and the shorter version initiated from a downstream in-frame start codon lacks the N-terminal amino acids of the full-length isoform version (Kozak, 2002).
Since the first discovery of alternative translational initiation, a small, yet growing, number of mRNAs initiating translation from alternative start codons have been reported (Kozak, 2002). Alternative translational initiation is an important cellular mechanism in the expression process of mRNAs. Experimental studies of individual genes revealed cases of functional differences (attributed to insertions, deletions or substitutions of functional protein domains and selection of the cellular localization) among alternatively initiated isoforms (Lock et al., 1991; Luque et al., 1998; Perry et al., 2000). However, a systematic collection of existing observations on alternative translational initiation events is still lacking, which limits the progress in the functional analysis of this important mechanism. The need for such a resource is clear with respect to the important fact that translational polymorphism acts as a potential source of proteins variety (Kochetov and Sarai, 2004; Kochetov et al., 2005). In this paper, we establish a database named ATID (alternative translational initiation database) as a systematic collection of all publicly available genes with alternative translational initiation, including their alternative translational isoforms and detailed annotations.
ATID is a web-oriented database that uses a WWW-browser interface to access data under the SQL framework. The records of alternative translational events are converted and stored in a MySQL database program (http://www.mysql.com). The web page allows interaction between the users and the data application. Indexing key identifiers of the database optimizes batch queries from the HTTP web page interface. When a HTTP request is triggered, we can import items of SQL database into the application. Then, the results are sent in the format of HTML to the website.
The database contains 650 alternatively translated protein products belonging to a total of 300 genes. These records of alternative translational initiation were mainly collected from the Swiss-Prot protein database (Bairoch and Apweiler, 2000) and the Entrez protein database on NCBI (http://www.ncbi.nlm.nih.gov/Entrez/). Some other data, the information of 89 alternative translational initiation events was extracted from published research literature. The genes involve many species including Homo sapiens, Mus musculus, Bos taurus, Saccharomyces cerevisiae, Virus, etc.
An overview is created to illustrate the database interface on web pages. A tree structure of the species classifying the database entries is constructed and all the entries can be browsed according to the species they belong to. Each entry includes detailed information of the gene including the accession identifier, species, gene name, publication or database references and other information on the isoform products. By clicking on isoform ID, the information on alternative translational products will be displayed. Elements such as isoelectric point (pI) value, molecular weight and sequence information are designated to annotate the isoform products of the gene. The distributions of the domain content in the amino acids sequence, which concerns with the protein function, are scanned by the family matching system Pfam 16.0 (http://pfam.wustl.edu) (Bateman et al., 2002) with a given threshold of the E-value and are displayed for each isoform product. Also, a topological structure graph is given to help users understand the process of alternative translational initiation from an mRNA to different isoforms. Figure 1A shows the topological structure of the FGF2 gene in H.sapiens as an example. In Figure 1A, there are four shorter isoforms lacking the N-terminal amino acids fragments from the original 30.8 kDa full-length isoform. The annotation page for the 22.6 kDa isoform of FGF2 is shown in Figure 1B as an example. The database supports two other ways of querying the entries besides directly accessing the entries on the species tree. One is by keyword query and the other is by query of sequence similarity. In the former way, keywords such as the accession number and the gene name can be submitted. In the latter case, the nucleotide or amino acid sequences can be submitted in FASTA format through the web interface. The submitted sequence will be compared with the sequences in the database by the BLAST program (Altschul et al., 1997). The cluster of database entries that contains the most similar sequences will be returned in a table format.
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The ATID database provides a resource for future biological analyses of alternative translational initiation, including the development of computational methods for the functional analysis of alternative translational initiation. It presents the most comprehensive collection of alternative translational events to date, and it will be updated timely by continuous collection of new records appearing in the literature and other databases. More features like the prediction of genes with putative alternative translational initiation and their functions will be developed in future updates of the database.
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Acknowledgments |
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We thank Dr X. Zhang for his help in the writing. This work was partially supported by the NSFC grants (60171038 and 60234020) and the PhD student grant of Tsinghua University.
Conflict of Interest: none declared.
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FOOTNOTES |
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Present address: Center of Excellence in Bioinformatics, University at Buffalo, 901 Washington Street, Buffalo, NY 14203, USA. 
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
Received on June 5, 2005; revised on September 15, 2005; accepted on October 3, 2005
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REFERENCES |
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TOPABSTRACTREFERENCES |
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Altschul, S.F., et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res, . 25, 3389–3402
Bairoch, A. and Apweiler, R. (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res, . 28, 45–48
Bateman, A., et al. (2002) The Pfam protein families database. Nucleic Acids Res, . 30, 276–280
Kochetov, A.V. and Sarai, A. (2004) Translational polymorphism as a potential source of plant proteins variety in Arabidopsis thaliana. Bioinformatics, 20, 445–447
Kochetov, A.V., et al. (2005) The role of alternative translation start sites in the generation of human protein diversity. Mol. Genet. Genomics, 273, 491–496[CrossRef][Web of Science][Medline].
Kozak, M. (2002) Pushing the limits of the scanning mechanism for initiation of translation. Gene, 299, 1–34[CrossRef][Web of Science][Medline].
Lock, P., et al. (1991) Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization. Mol. Cell. Biol, . 11, 4363–4370
Luque, C.M., et al. (1998) An alternative domain determines nuclear localization in multifunctional protein 4.1. J. Biol. Chem, . 273, 11643–11649
Perry, M.E., et al. (2000) P76MDM2 inhibits the ability of p90MDM2 to destabilize p53. J. Biol. Chem, . 275, 5733–5738
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