Bifunctional 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphate 2-phosphatase <p>Fructose 2,6-bisphosphate is a signal molecule important for control of glycolysis. Its formation from fructose 6-phosphate and Mg-ATP is catalysed by 6-phosphofructo-2-kinase (<db_xref db="EC" dbkey="2.7.1.105"/>), while its degradation is catalysed by fructose-2,6-bisphosphatase (<db_xref db="EC" dbkey="3.1.3.46"/>). In plants and animals these reactions are effected by a bifunctional, two-domain enzyme. Some of the related proteins found in fungi and trypanosomatids have lost one or the other activity--though still possessing the two-domain structure--indicating that the gene fusion that produced the bifunctional molecule occurred early in eukaryote evolution [<cite idref="PUB00027758"/>]. Yeast 6-phosphofructo-2-kinase Pfk26p, for example, has about 42% identity with the bifunctional enzyme from rat liver, with extra sequence at each end. Although the sequences are very similar in the bisphosphatase domain, the essential histidine of the liver enzyme is replaced by a serine in yeast, explaining the apparent lack of bisphosphatase activity. Also, the yeast enzyme, which is activated by protein kinase A, has a putative phosphorylation site near its carboxyl end and lacks the N-terminal phosphorylation sequence involved in inhibition of the liver enzyme [<cite idref="PUB00027761"/>].</p> <p>In animals, yeast, and trypanosomatids, several isozymes (and sometimes several isoforms of each) with different kinetic and regulatory mechanisms are found, allowing for adaptation to various hormonal, nutritional, and environmental states. The major mammalian isoenzymes are characteristic of liver, heart, brain/placenta, and testis. In contrast, only a single gene has been found in plants [<cite idref="PUB00027758"/>].</p> <p>The related <db_xref db="INTERPRO" dbkey="IPR014379"/> represents a small group of fungal proteins from which the fructose-2,6-bisphosphatase domain has been lost.</p>