Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 6;51(D1):D328-D336.
doi: 10.1093/nar/gkac899.

The new uORFdb: integrating literature, sequence, and variation data in a central hub for uORF research

Felix Manske  1 , Lynn Ogoniak  1 , Lara Jürgens  2 , Norbert Grundmann  1 , Wojciech Makałowski  1 , Klaus Wethmar  2
Affiliations

The new uORFdb: integrating literature, sequence, and variation data in a central hub for uORF research

Felix Manske et al. Nucleic Acids Res. .

Abstract

Upstream open reading frames (uORFs) are initiated by AUG or near-cognate start codons and have been identified in the transcript leader sequences of the majority of eukaryotic transcripts. Functionally, uORFs are implicated in downstream translational regulation of the main protein coding sequence and may serve as a source of non-canonical peptides. Genetic defects in uORF sequences have been linked to the development of various diseases, including cancer. To simplify uORF-related research, the initial release of uORFdb in 2014 provided a comprehensive and manually curated collection of uORF-related literature. Here, we present an updated sequence-based version of uORFdb, accessible at https://www.bioinformatics.uni-muenster.de/tools/uorfdb. The new uORFdb enables users to directly access sequence information, graphical displays, and genetic variation data for over 2.4 million human uORFs. It also includes sequence data of >4.2 million uORFs in 12 additional species. Multiple uORFs can be displayed in transcript- and reading-frame-specific models to visualize the translational context. A variety of filters, sequence-related information, and links to external resources (UCSC Genome Browser, dbSNP, ClinVar) facilitate immediate in-depth analysis of individual uORFs. The database also contains uORF-related somatic variation data obtained from whole-genome sequencing (WGS) analyses of 677 cancer samples collected by the TCGA consortium.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Scaled graphical model for the human MIEF1 TLS and uORFs in the transcript NM_019008.6. The image shows all ATG and aTIS uORFs in uORFdb in the three reading frames (RF1 to RF3) of the transcript. Canonical ATG uORFs with an AUG uStart codon are highlighted in orange by default. The CDS is depicted as a bold blue bar, the TLS as a thin blue bar. The scale of 100 base pairs (BP) is indicated at the top, but only applies to the TLS. The uORF ATG.3 in reading frame three of NM_019008.6 encodes the uPeptide predicted by Vanderperre and coworkers (48). Note that in the MIEF1 transcript NM_001394030.1 the main protein is initiated by the ATG.3 uORF, indicated here by the asterisk symbol. Additionally, the image shows the view buttons and filters at the top that can be used to adjust the display.
Figure 2.
Figure 2.
Screenshot of the ‘uORFs’ view showing details for the five ATG uORFs in uORFdb in transcript NM_019008.6 of the human gene MIEF1. Views can be freely changed using the view buttons (red box). The ‘Variants’ view is greyed out, as there were no somatic cancer variants associated with the displayed uORFs. uORFs can be filtered by start and stop codon (blue box). The uORF ATG.3 encodes the uPeptide predicted by Vanderperre and coworkers (48). Note that in the MIEF1 transcript NM_001394030.1, the main protein is initiated by ATG.3, as indicated by the asterisk symbol in the ‘Start codon’ column. The image also shows the export options to Excel and CSV format and the blue ‘Model’ button that can be used to display the uORF model of all uORFs in the current view. The start codon inside each Kozak sequence is highlighted in red. For convenience, we cropped the screenshot after the ‘Reading frame’ column.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mueller P.P., Hinnebusch A.G.. Multiple upstream AUG codons mediate translational control of GCN4. Cell. 1986; 45:201–207. - PubMed
    1. Abastado J.P., Miller P.F., Jackson B.M., Hinnebusch A.G.. Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control. Mol. Cell. Biol. 1991; 11:486–496. - PMC - PubMed
    1. Sundaram A., Grant C.M.. A single inhibitory upstream open reading frame (uORF) is sufficient to regulate Candida albicans GCN4 translation in response to amino acid starvation conditions. RNA. 2014; 20:559–567. - PMC - PubMed
    1. Lu P.D., Harding H.P., Ron D.. Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. J. Cell Biol. 2004; 167:27–33. - PMC - PubMed
    1. Vattem K.M., Wek R.C.. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 2004; 101:11269–11274. - PMC - PubMed

Publication types