The Case of EC 3.5.3.13 in Histidine Degradation

Ross Overbeek, Fellowship for Interpretation of Genomes

I recently constructed a subsystem for histidine degradation as an exercise. KEGG shows the pathway as containing three initial steps:

1. Histidine ammonia-lyase (EC 4.3.1.3)
2. Urocanate hydratase (EC 4.2.1.49)
3. Imidazolonepropionase (EC 3.5.2.7)

These are followed by three alternatives:

• Glutamate formiminotransferase (EC 2.1.2.5),
• Formiminoglutamase (EC 3.5.3.8) and
• N-formylglutamate deformylase (EC 3.5.1.68) followed by Formiminoglutamic iminohydrolase (EC 3.5.3.13)

That is, the pathway will be complete if you have (1,2,3) and any one of these last three alternatives. What I discovered is that there is no sequence in entrez (or KEGG) with the function EC 3.5.3.13. There are numerous (over 20) beautiful clusters with an obvious candidate for 3.5.3.13. For example, in Caulobacter crescentus CB15 the gene with RefSeq id: NP_419777.1 and UniProt id: uni|Q9A9L9 is, I assert, a gene playing the functional role Formiminoglutamic iminohydrolase (EC 3.5.3.13).