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. 2012 May 20;2012:bas025.
doi: 10.1093/database/bas025. Print 2012.

HAltORF: A Database of Predicted Out-Of-Frame Alternative Open Reading Frames in Human

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Free PMC article

HAltORF: A Database of Predicted Out-Of-Frame Alternative Open Reading Frames in Human

Benoît Vanderperre et al. Database (Oxford). .
Free PMC article

Abstract

Human alternative open reading frames (HAltORF) is a publicly available and searchable online database referencing putative products of out-of-frame alternative translation initiation (ATI) in human mRNAs. Out-of-frame ATI is a process by which a single mRNA encodes independent proteins, when distinct initiation codons located in different reading frames are recognized by a ribosome to initiate translation. This mechanism is largely used in viruses to increase the coding potential of small viral genomes. There is increasing evidence that out-of-frame ATI is also used in eukaryotes, including human, and may contribute to the diversity of the human proteome. HAltORF is the first web-based searchable database that allows thorough investigation in the human transcriptome of out-of-frame alternative open reading frames with a start codon located in a strong Kozak context, and are thus the more likely to be expressed. It is also the first large scale study on the human transcriptome to successfully predict the expression of out-of-frame ATI protein products that were previously discovered experimentally. HAltORF will be a useful tool for the identification of human genes with multiple coding sequences, and will help to better define and understand the complexity of the human proteome. Database URL: http://haltorf.roucoulab.com/.

Figures

Figure 1
Figure 1
AltPrP, a typical example of AltORFs in the HAltORF database. All mRNAs produced from the PRNP gene have the same reference ORF (nt 1–762, gray box) which encodes the prion protein (PrPC) in the +1 reading frame. An AltORF (white box) is present in the +3 reading frame (nt 90–309). Similar to all AltORFs present in the database, the alternative prion protein (AltPrP) encoding AltORF is entirely included in the CDS of the reference protein, and encodes a protein longer than 24 amino acids (minimum size threshold). Additionally, its AUG codon is in a different reading frame than the reference protein, and is located in an optimal Kozak context (shown in bold; consensus: A/GNNAUGG).
Figure 2
Figure 2
Snapshot of a typical search and associated results pages. (1) Search by gene (DEFB104A, which encodes the β-defensin 104 protein). (2) The number of corresponding AltORFs is indicated, and details on each AltORF are summarized in a table. Although this is not the case for this particular example, note that for a single gene, all AltORFs present in each transcript variants would be listed. The reference ORF is by definition in the +1 frame, and the alternative ORFs is in the +2 frame in this example. The nucleotide numbers indicating the location of the ORFs are the first nucleotide of the start codon, and the first nucleotide of the stop codon, respectively. (3) A detailed result page is available for each AltORF through the ‘View’ link. (4) In the detailed result page, basic information on the gene and mRNA of origin as well as the associated reference protein are displayed along with links to GenBank for each of these items (not shown). An alignment of the reference (blue letters) and alternative (green letters) protein sequences on the reference mRNA sequence (black letters) is provided.

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