Proteins of unknown biochemical function: A persistent problem and a roadmap to help overcome it

Thomas D. Niehaus, Antje M.K. Thamm, Valérie De Crécy-Lagard, Andrew D. Hanson

Research output: Contribution to journalArticlepeer-review


The number of sequenced genomes is rapidly increasing, but functional annotation of the genes in these genomes lags far behind. Even in Arabidopsis (Arabidopsis thaliana), only approximately 40% of enzyme- and transporter-encoding genes have credible functional annotations, and this number is even lower in nonmodel plants. Functional characterization of unknown genes is a challenge, but various databases (e.g. for protein localization and coexpression) can be mined to provide clues. If homologous microbial genes exist—and about one-half the genes encoding unknown enzymes and transporters in Arabidopsis have microbial homologs—cross-kingdom comparative genomics can powerfully complement plant-based data. Multiple lines of evidence can strengthen predictions and warrant experimental characterization. In some cases, relatively quick tests in genetically tractable microbes can determine whether a prediction merits biochemical validation, which is costly and demands specialized skills.

Original languageEnglish (US)
Pages (from-to)1436-1442
Number of pages7
JournalPlant physiology
Issue number3
StatePublished - Nov 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 American Society of Plant Biologists. All rights Reserved.


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