If you have used BioCyc, you probably noticed that many reactions have EC numbers printed next to them. EC numbers are everywhere – in the primary literature, in annotated genomes, in databases, in online encyclopedias. Where do they come from and what exactly do they mean?
A Bit of History
In the early days the naming of enzymes was not systematic. As a result, many different enzymes were given the same name and, on the other hand, several different names were assigned to the same enzyme. Many of the names were not particularly helpful; for example, the enzyme now known as EC 18.104.22.168, NADPH dehydrogenase, was originally named “old yellow enzyme”.
To sort out the mess, Dixon and Webb introduced a classification system in their 1958 book “Enzymes”, which was based on the reaction catalyzed by the enzyme. Although it was rather limited, it provided the foundation for the current classification system. At about the same time, the International Union of Biochemistry has decided to form an official international commission on enzymes to develop a better classification and naming system. The first full report of the commission was published in 1965, using a six-category system that is still used today. Although this is not the place to describe classification principles, in general each enzyme receives a unique four-component identification number that not only identifies it, but also provides insight into the enzymatic activity of the enzyme. Each EC entry provides additional information such as lists of names and synonyms, references, and often commentary. Full details about the principles of the classification system can be found at http://enzyme-database.org/rules.php and https://en.wikipedia.org/wiki/Enzyme_Commission_number.
Fast forward 50 years, and the Enzyme Commission (EC) is still going strong. The importance and usefulness of the EC numbers has only increased with time. With the explosion in sequencing volume, having an accurate genome annotation has become critical, and EC numbers provide a well-defined, non-ambiguous method for annotation of enzyme function. Software packages such as Pathway Tools make the most out of this information, assigning the appropriate reactions to the annotated genes based on their EC numbers when building metabolic networks for newly-sequenced genomes. The content of the enzyme list, which used to be published in books, is made available through two online databases that are updated several times a year. A searchable MySQL version of the database, including downloadble data in multiple formats, is available at the ExplorEnz database at http://enzyme-database.org. More than 5600 enzymes are currently classified, and hundreds are added each year.
Who is the EC?
The Enzyme Commission is now part of the IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN). It consists of a small number of experts who volunteer their time to the project. Active members (listed alphabetically) include K. Axelsen (Switzerland), R. Cammack (UK), R. Caspi (USA), M. Kotera (Japan), A. McDonald (Ireland), G.P. Moss (UK), D. Schomburg (Germany), I. Schomburg (Germany), and K.F. Tipton (Ireland). The commission members are using an online curation system that was developed by A. McDonald, called ExplorEnz. Members of the committee continue to classify new enzymes, modify existing entries as new information becomes available, and extend or modify the classification rules to accommodate new challenges.
If you would like to request a new EC entry for an enzyme that hasn’t been classified yet, or submit an error or update report about an existing entry, submission forms are available at http://enzyme-database.org/forms.php. Since MetaCyc curator R. Caspi is a member of the EC, you are also welcome to send EC-related questions or comments to biocyc-support@AI.SRI.COM.
- Dixon, M. and Webb, E.C. (1958), Enzymes. Longmans Green, London, pp. 183–227.
- Tipton, K. and Boyce, S. (2000) History of the enzyme nomenclature system. Bioinformatics, 16, 34-40.
- McDonald, A.G., Boyce, S. and Tipton, K.F. (2009) ExplorEnz: the primary source of the IUBMB enzyme list. Nucleic Acids Res, 37, D593-597.
- McDonald, A.G. and Tipton, K.F. (2014) Fifty-five years of enzyme classification: advances and difficulties. Febs J, 281, 583-592.