ATP-dependent 6-phosphofructokinase, eukaryotic-type (IPR009161)

Short name: 6-Pfructokinase_euk

Family relationships


Phosphofructokinase (PFK) catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate, which then enters the Embden-Meyerhof pathway. PFK is a key regulatory enzyme in glycolysis.

This entry represent eukaryotic type of ATP-dependent PFKs. They belong to the PFK domain superfamily of proteins, which also includes pyrophosphate (PPi)-dependent PFKs (IPR012004) and bacterial ATP-dependent PFKs (IPR012003). Unlike the bacterial PFKs, eukaryotic PFKs have a large N-terminal extension bearing an additional PFK domain [PMID: 10091602]. Proteins in this entry largely resemble group E PFKs [PMID: 14585511].

Classification of PFK proteins revealed that major functional specialization can occur by mutation in one single amino acid residue. Based on the energy phosphoryl donors, the PFKs can be divided into two groups: ATP dependent PFKs (ATP-PFK) and inorganic pyrophosphate dependent PFKs (PPi-PFK). The eukaryotic ATP-PFKs are twice the size of the prokaryotic ATP-PFKs and have arisen through gene duplication and fusion of the ancestral bacterial gene. Not surprisingly, eukaryotic ATP-PFK homodimers are essentially equivalent to prokaryotic homotetramers. The PPi-PFKs, unlike the majority of ATP-PFKs, are not monophyletic in origin. The ability to use ATP or PPi is suggested to be dependent on the presence of one invariant glycine residue; therefore it is not surprising that the ability to utilise PPi has arisen more than once, and some recent changes in the phosphoryl donor (ATP to PPi) can be seen in several bacterial PFKs from IPR012003. It has been hypothesized that PPi-PFK may provide organisms niche-specific advantages, because the PPi phosphoryl donor allows both conservation of ATP and reaction reversibility; thus, it can function in both glycolysis and gluconeogenesis. It is likely that these enzymes evolved from the irreversible glycolysis form (ATP-dependent) towards the reversible reaction form (PPi-dependent). If a single point mutation can induce a change of the phosphoryl donor, it could be argued that the opposite mutation could also take place, thereby converting a PPi-PFK into an ATP-PFK. An example of such opposite mutation can be found in IPR012004 [PMID: 2139864, PMID: 8326866].

GO terms

Biological Process

GO:0006096 glycolytic process

Molecular Function

GO:0003872 6-phosphofructokinase activity
GO:0005524 ATP binding

Cellular Component

GO:0005737 cytoplasm

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.