ArticleProceedings of the National Academy of Sciences of the United States of America2015
Unexpected features of the dark proteome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis.British journal of cancer · 2022Pooled it
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- The microbial unknome, a repertoire for microbial chatting?Heredity · 2026Review
- De novo Transcriptome Assembly of the Venom Gland of Conus inscriptus Provides Insights into its Conotoxin Repertoire.Marine biotechnology (New York, N.Y.) · 2026Article
- Integrative structural interactomics reveals protein organization and structure in a giant virus.Nature communications · 2026Article
- On the state of protein function prediction: a report on the fourth CAFA challenge.bioRxiv : the preprint server for biology · 2026Article
- Shining light on the dark proteome with unstructural biology.Current research in structural biology · 2026Article
- Neurochondrin drives colorectal cancer progression by modulating the PODXL-Ezrin axis and mitochondrial function.Cell death & disease · 2026Article
- Functional Assessment of Orphan Proteins in theMicroorganisms · 2026Article
- Probing the dark energy in the functional protein universe.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- DisProt in 2026: enhancing intrinsically disordered proteins accessibility, deposition, and annotation.Nucleic acids research · 2026Article
- Critical Assessment of Protein Intrinsic Disorder Round 3 - Predicting Disorder in the Era of Protein Language Models.Proteins · 2026Article
- Protein language models uncover carbohydrate-active enzyme function in metagenomics.BMC bioinformatics · 2025Article
- Artificial intelligence to shed light on the algal dark proteomes.Patterns (New York, N.Y.) · 2025Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- The Analysis ofCurrent issues in molecular biology · 2025Article
- Learning Universal Representations of Intermolecular Interactions with ATOMICA.bioRxiv : the preprint server for biology · 2025Article
- Increasing Proteome Coverage Through a Reduction in Analyte Complexity in Single-Cell Equivalent Samples.Journal of proteome research · 2025Article
- Review
- Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF.Nucleic acids research · 2025Article
47 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
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We surveyed the "dark" proteome-that is, regions of proteins never observed by experimental structure determination and inaccessible to homology modeling. For 546,000 Swiss-Prot proteins, we found that 44-54% of the proteome in eukaryotes and viruses was dark, compared with only ∼14% in archaea and bacteria. Surprisingly, most of the dark proteome could not be accounted for by conventional explanations, such as intrinsic disorder or transmembrane regions. Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions, but a subset showed distinct and largely unexpected features, such as association with secretion, specific tissues, the endoplasmic reticulum, disulfide bonding, and proteolytic cleavage. Dark proteins also had short sequence length, low evolutionary reuse, and few known interactions with other proteins. These results suggest new research directions in structural and computational biology.
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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.