ArticlePloS one2013
Direct detection of alternative open reading frames translation products in human significantly expands the proteome.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.
- Pooled it
- Identification of unannotated microproteins involved in endothelial cell homeostasis, dysfunction, and vascular disease.Cardiovascular research · 2026Article
- STREMI: a dual-function upstream ORF-encoded regulator of mitochondrial cristae architecture.EMBO reports · 2026Article
- Progressive Supranuclear Palsy PERK Haplotype B Selectively Translates DLX1 Promoting Tau Toxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- Implication of Epigenetic Alterations of ZEB1 in Colorectal Cancer (CRC) Pathogenesis and Therapy Development.Current issues in molecular biology · 2026Review
- Alternatively Spliced Dual-Coding Regions Contribute to the Human Gene Regulatory Program.bioRxiv : the preprint server for biology · 2026Article
- Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.Journal of molecular evolution · 2026Article
- Protein tandem repeats that produce frameshifts can generate new structural states and functions.The FEBS journal · 2026Article
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 2026Article
- The 'non-conventional' peptidome: A new layer in plant regulatory mechanisms.Plant communications · 2025Review
- Chasing the Ghost Proteome in the Dark Matter.Molecular & cellular proteomics : MCP · 2025Review
- Article
- The dual-coding gene SLC35A4 protects against oxidative stress.Protein science : a publication of the Protein Society · 2025Article
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- A large-scale sORF screen identifies putative microproteins involved in cancer cell fitness.iScience · 2025Article
- Non-canonical ORFs-derived protein products in mitochondria: A multifaceted exploration of their functions in health and disease.Protein science : a publication of the Protein Society · 2025Review
- Microproteins in cancer: identification, biological functions, and clinical implications.Trends in genetics : TIG · 2025Review
- Evaluation of Eukaryotic mRNA Coding Potential.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and disease.bioRxiv : the preprint server for biology · 2024Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
A fully mature mRNA is usually associated to a reference open reading frame encoding a single protein. Yet, mature mRNAs contain unconventional alternative open reading frames (AltORFs) located in untranslated regions (UTRs) or overlapping the reference ORFs (RefORFs) in non-canonical +2 and +3 reading frames. Although recent ribosome profiling and footprinting approaches have suggested the significant use of unconventional translation initiation sites in mammals, direct evidence of large-scale alternative protein expression at the proteome level is still lacking. To determine the contribution of alternative proteins to the human proteome, we generated a database of predicted human AltORFs revealing a new proteome mainly composed of small proteins with a median length of 57 amino acids, compared to 344 amino acids for the reference proteome. We experimentally detected a total of 1,259 alternative proteins by mass spectrometry analyses of human cell lines, tissues and fluids. In plasma and serum, alternative proteins represent up to 55% of the proteome and may be a potential unsuspected new source for biomarkers. We observed constitutive co-expression of RefORFs and AltORFs from endogenous genes and from transfected cDNAs, including tumor suppressor p53, and provide evidence that out-of-frame clones representing AltORFs are mistakenly rejected as false positive in cDNAs screening assays. Functional importance of alternative proteins is strongly supported by significant evolutionary conservation in vertebrates, invertebrates, and yeast. Our results imply that coding of multiple proteins in a single gene by the use of AltORFs may be a common feature in eukaryotes, and confirm that translation of unconventional ORFs generates an as yet unexplored proteome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.