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Literature summary extracted from

  • Gizak, A.; Duda, P.; Wisniewski, J.; Rakus, D.
    Fructose-1,6-bisphosphatase from a glucose metabolism enzyme to multifaceted regulator of a cell fate (2019), Adv. Biol. Regul., 72, 41-50.
    View publication on PubMed

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.1.3.11 AMP binding of AMP, and presumably NAD+, stabilizes an inactive, T-state of FBPase Mammalia
3.1.3.11 Ca2+ slight inhibition of isozyme FBP1. Presence of glutamic acid at position 69 ensures strong binding of Ca2+ to the muscle FBPase, which in turn disrupts the proper interaction of catalytic divalent cations (e.g. Mg2+) with the substrate in the catalytic site. Ectothermal vertebrates FBP2 is significantly less sensitive to Ca2+ than warm-blooded animals being still more sensitive to the cation than FBP1; strong inhibition Mammalia
3.1.3.11 fructose 2,6-bisphosphate
-
 Mammalia
3.1.3.11 additional information while the inactive T-states of FBP1 and FBP2 are similar, the active R-state of FBP2 adopts the cruciform structure while in the liver enzyme FBP1, the R-state is planar. Distinct sensitivity of the two isozymes towards effectors; while the inactive T-states of FBP1 and FBP2 are similar, the active R-state of FBP2 adopts the cruciform structure, while in the liver enzyme FBP1, the R-state is planar. Distinct sensitivity of the two isozymes towards effectors Mammalia
3.1.3.11 NAD+ binding of AMP, and presumably NAD+, stabilizes an inactive, T-state of FBPase Mammalia

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.1.3.11 cytosol
-
 Mammalia 5829
-
3.1.3.11 cytosol probably Mammalia 5829
-
3.1.3.11 additional information in HL-1 cardiomyocytes, nuclear transport of FBP2 is stimulated by norepinephrine acting through beta1 receptors. Inhibition of PI3K results in FBP2 withdrawal from the nuclei of HL-1 cells. FBP2 nuclear localisation and active nucleo-cytoplasmic shuttling of FBP2 in cardiomyocytes Mammalia
-
-
3.1.3.11 additional information FBP1 nuclear localisation and active nucleo-cytoplasmic shuttling of FBP1, nucleo-cytoplasmic shuttling is impaired during diabetes Mammalia
-
-
3.1.3.11 nucleus the mechanism of nuclear import of FBP2 relies on well-defined and studied canonical motif KKKGK. FBP2 accumulates in nuclei upon PKA and PI3K activation and during the S phase of the cell cycle Mammalia 5634
-
3.1.3.11 nucleus the mechanism of FBP2 export from nuclei involves the hydrophobic motif LGEFVL (190-195), a hypothetical candidate for nuclear export sequence (NES), located in interface of upper and lower dimer and inaccessible to export machinery Mammalia 5634
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.1.3.11 Co2+ required for catalytic activity of FBP2 Mammalia
3.1.3.11 Co2+ required for catalytic activity of FBP1 Mammalia
3.1.3.11 Mg2+ required for catalytic activity of FBP2 Mammalia
3.1.3.11 Mg2+ required for catalytic activity of FBP1. Presence of glutamic acid at position 69 ensures strong binding of Ca2+ to the muscle FBPase, which in turn disrupts the proper interaction of catalytic divalent cations (e.g. Mg2+) with the substrate in the catalytic site Mammalia
3.1.3.11 additional information divalent cations such as Mg2+, Mn2+, Co2+ or Zn2+ are indispensable for catalysis, while Ca2+ is a strong inhibitor of the muscle FBPase having only minor effect on the liver isoform. Distinct sensitivity of the two isozymes towards effectors Mammalia
3.1.3.11 additional information divalent cations such as Mg2+, Mn2+, Co2+ or Zn2+ are indispensable for catalysis while Ca2+ is a strong inhibitor of the muscle FBPase having only minor effect on the liver isoform. Distinct sensitivity of the two isozymes towards effectors Mammalia
3.1.3.11 Zn2+ required for catalytic activity of FBP2 Mammalia
3.1.3.11 Zn2+ required for catalytic activity of FBP1 Mammalia

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.3.11 D-fructose 1,6-bisphosphate + H2O Mammalia
-
 D-fructose 6-phosphate + phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.1.3.11 Mammalia
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.1.3.11 breast cancer cell
-
 Mammalia
-
3.1.3.11 cardiac muscle fiber
-
 Mammalia
-
3.1.3.11 HL-1 cell
-
 Mammalia
-
3.1.3.11 kidney
-
 Mammalia
-
3.1.3.11 kidney cancer cell
-
 Mammalia
-
3.1.3.11 KLN205 cell
-
 Mammalia
-
3.1.3.11 liver liver isozyme FBP1 Mammalia
-
3.1.3.11 lung squamous cell carcinoma cell
-
 Mammalia
-
3.1.3.11 additional information ubiquitous expression of FBP2, muscle FBPase (FBP2), encoded by gene fbp2, is widely expressed in vertebrate cells, not only in glyconeogenic ones (e.g. striated muscle fibres) but also in cells such as neurons which are not thought to synthesize glycogen from carbohydrate precursors. FBP2 is also expressed in cells predominantly producing the liver isozyme, e.g. in the liver itself Mammalia
-
3.1.3.11 additional information liver FBPase (FBP1) is expressed mainly in gluconeogenic organs Mammalia
-
3.1.3.11 neonate
-
 Mammalia
-
3.1.3.11 retina neonatal retina cell Mammalia
-
3.1.3.11 skeletal muscle muscle isozyme FBP2 Mammalia
-
3.1.3.11 skeletal muscle satellite cell
-
 Mammalia
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.3.11 D-fructose 1,6-bisphosphate + H2O
-
 Mammalia D-fructose 6-phosphate + phosphate
-
 ?

Subunits

EC Number Subunits Comment Organism
3.1.3.11 homotetramer 4 * 37000, SDS-PAGE Mammalia
3.1.3.11 additional information mammalian FBPases are homotetrameric enzymes with a subunit molecular mass of about 37 kDa. The tertiary structure of each monomer is composed of two domains, a domain containing the substrate binding site (FBP domain) and an allosteric domain which may interact with AMP and NAD+ (AMP domain). Binding of AMP, and presumably NAD+, stabilizes an inactive, T-state of FBPase Mammalia
3.1.3.11 additional information mammalian FBPases are homotetrameric enzymes with a subunit molecular mass of about 37 kDa. The tertiary structure of each monomer is composed of two domains, a domain containing the substrate binding site (FBP domain) and an allosteric domain which may interact with AMP and NAD+ (AMP domain). The wild-type FBP1 tetramer exists in at least two distinct quaternary states called R and T. Binding of AMP, and presumably NAD+, stabilizes an inactive, T-state of FBPase Mammalia

Synonyms

EC Number Synonyms Comment Organism
3.1.3.11 FBP1
-
 Mammalia
3.1.3.11 FBP2
-
 Mammalia
3.1.3.11 fructose-1,6-bisphosphatase 1
-
 Mammalia
3.1.3.11 fructose-1,6-bisphosphatase 2
-
 Mammalia

General Information

EC Number General Information Comment Organism
3.1.3.11 evolution invertebrate genomes contain a single fbp locus. In vertebrates, there are two distinct genes, fbp1 and fbp2, encoding two FBPase isozymes. Liver FBPase (FBP1), the protein product of the fbp1 gene, is expressed mainly in gluconeogenic organs, while muscle FBPase (FBP2), encoded by gene fbp2, is widely expressed in vertebrate cells, not only in glyconeogenic ones (e.g. striated muscle fibres) but also in cells such as neurons which are not thought to synthesize glycogen from carbohydrate precursors. FBP2 is also expressed in cells predominantly producing the liver isozyme, e.g. in the liver itself. In vertebrates, the two FBPase isozymes evolved to play distinct cellular roles Mammalia
3.1.3.11 evolution invertebrate genomes contain a single fbp locus. In vertebrates, there are two distinct genes, fbp1 and fbp2, encoding two FBPase isozymes. Liver FBPase (FBP1), the protein product of the fbp1 gene, is expressed mainly in gluconeogenic organs, while muscle FBPase (FBP2), encoded by fbp2, is widely expressed in vertebrate cells, not only in glyconeogenic ones (e.g. striated muscle fibres) but also in cells such as neurons which are not thought to synthesize glycogen from carbohydrate precursors. FBP2 is also expressed in cells predominantly producing the liver isozyme, e.g. in the liver itself. In vertebrates, the two FBPase isozymes evolved to play distinct cellular roles Mammalia
3.1.3.11 malfunction the block of the cell cycle progression by withdrawal of serum from a culture medium which results in a quiescent, G0-like cell stage not only stimulates FBP2 export from nuclei to cytoplasm but also significantly reduces the amount of the enzyme simultaneously elevating the level of mRNA for FBP2 Mammalia
3.1.3.11 malfunction the cells with partially silenced FBP2 expressions are almost 2- and 4-times more viable than, respectively, wild-type cells and cells overexpressing FBP2 Mammalia
3.1.3.11 additional information the tertiary structure of each monomer is composed of two domains, a domain containing the substrate binding site (FBP domain) and an allosteric domain which may interact with AMP and NAD+ (AMP domain). Binging of AMP, and presumably NAD+, stabilizes an inactive, T-state of FBPase. Divalent cations such as Mg2+, Mn2+, Co2+ or Zn2+ are indispensable for catalysis while Ca2+ is a strong inhibitor of the muscle FBPase having only minor effect on the liver isoform. While the inactive T-states of FBP1 and FBP2 are similar, the active R-state of FBP2 adopts the cruciform structure while in the liver enzyme, the R-state is planar Mammalia
3.1.3.11 additional information the tertiary structure of each monomer is composed of two domains, a domain containing the substrate binding site (FBP domain) and an allosteric domain which may interact with AMP and NAD+ (AMP domain). Binding of AMP, and presumably NAD+, stabilizes an inactive, T-state of FBPase. Divalent cations such as Mg2+, Mn2+, Co2+ or Zn2+ are indispensable for catalysis while Ca2+ is a strong inhibitor of the muscle FBPase having only minor effect on the liver isoform. While the inactive T-states of FBP1 and FBP2 are similar, the active R-state of FBP2 adopts the cruciform structure while in the liver enzyme, the R-state is planar Mammalia
3.1.3.11 physiological function distinct allosteric regulation of isozyme FBP1 and FBP2, detailed overview. FBPases as regulators of nuclear processes Mammalia