ArticleNucleic acids research2017
Confronting the catalytic dark matter encoded by sequenced genomes.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- MACAW: a method for semi-automatic detection of errors in genome-scale metabolic models.Genome biology · 2025Article
- Metatranscriptomes-based sequence similarity networks uncover genetic signatures within parasitic freshwater microbial eukaryotes.Microbiome · 2025Article
- On knowing a gene: A distributional hypothesis of gene function.Cell systems · 2024Review
- Improved prediction of DNA and RNA binding proteins with deep learning models.Briefings in bioinformatics · 2024Article
- Rv2231c, a unique histidinol phosphate aminotransferase from Mycobacterium tuberculosis, supports virulence by inhibiting host-directed defense.Cellular and molecular life sciences : CMLS · 2024Article
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- Functional prediction of proteins from the human gut archaeome.ISME communications · 2024Article
- Identification and preliminary characterization of conserved uncharacterized proteins fromPlant direct · 2023Article
- Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.Biomolecules · 2023Article
- Functional unknomics: Systematic screening of conserved genes of unknown function.PLoS biology · 2023Article
- High-throughput Saccharomyces cerevisiae cultivation method for credentialing-based untargeted metabolomics.Analytical and bioanalytical chemistry · 2023Article
- ZNF330/NOA36 interacts with HSPA1 and HSPA8 and modulates cell cycle and proliferation in response to heat shock in HEK293 cells.Biology direct · 2023Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The post-genomic era has provided researchers with a deluge of protein sequences. However, a significant fraction of the proteins encoded by sequenced genomes remains without an identified function. Here, we aim at determining how many enzymes of uncertain or unknown function are still present in the Saccharomyces cerevisiae and human proteomes. Using information available in the Swiss-Prot, BRENDA and KEGG databases in combination with a Hidden Markov Model-based method, we estimate that >600 yeast and 2000 human proteins (>30% of their proteins of unknown function) are enzymes whose precise function(s) remain(s) to be determined. This illustrates the impressive scale of the 'unknown enzyme problem'. We extensively review classical biochemical as well as more recent systematic experimental and computational approaches that can be used to support enzyme function discovery research. Finally, we discuss the possible roles of the elusive catalysts in light of recent developments in the fields of enzymology and metabolism as well as the significance of the unknown enzyme problem in the context of metabolic modeling, metabolic engineering and rare disease research.
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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.