Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
127  structures 6789  species 0  interactions 11877  sequences 88  architectures

Family: F_bP_aldolase (PF01116)

Summary: Fructose-bisphosphate aldolase class-II

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Fructose-bisphosphate aldolase". More...

Fructose-bisphosphate aldolase Edit Wikipedia article

Fructose-bisphosphate aldolase
Fructose-bisphosphate aldolase octamer, Human
EC number4.1.2.13
CAS number9024-52-6
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Fructose-bisphosphate aldolase class-I
PDB 1fdj EBI.jpg
fructose 1,6-bisphosphate aldolase from rabbit liver
Fructose-bisphosphate aldolase class-II
PDB 1b57 EBI.jpg
class II fructose-1,6-bisphosphate aldolase in complex with phosphoglycolohydroxamate
Pfam clanCL0036

Fructose-bisphosphate aldolase (EC, often just aldolase, is an enzyme catalyzing a reversible reaction that splits the aldol, fructose 1,6-bisphosphate, into the triose phosphates dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). Aldolase can also produce DHAP from other (3S,4R)-ketose 1-phosphates such as fructose 1-phosphate and sedoheptulose 1,7-bisphosphate. Gluconeogenesis and the Calvin cycle, which are anabolic pathways, use the reverse reaction. Glycolysis, a catabolic pathway, uses the forward reaction. Aldolase is divided into two classes by mechanism.

The word aldolase also refers, more generally, to an enzyme that performs an aldol reaction (creating an aldol) or its reverse (cleaving an aldol), such as Sialic acid aldolase, which forms sialic acid. See the list of aldolases.

Mechanism and structure

Class I proteins form a protonated Schiff base intermediate linking a highly conserved active site lysine with the DHAP carbonyl carbon. Additionally, tyrosine residues are crucial to this mechanism in acting as stabilizing hydrogen acceptors. Class II proteins use a different mechanism which polarizes the carbonyl group with a divalent cation like Zn2+. The Escherichia coli galactitol operon protein, gatY, and N-acetyl galactosamine operon protein, agaY, which are tagatose-bisphosphate aldolase, are homologs of class II fructose-bisphosphate aldolase. Two histidine residues in the first half of the sequence of these homologs have been shown to be involved in binding zinc.[1]

The protein subunits of both classes each have an α/β domain folded into a TIM barrel containing the active site. Several subunits are assembled into the complete protein. The two classes share little sequence identity.

With few exceptions only class I proteins have been found in animals, plants, and green algae.[2] With few exceptions only class II proteins have been found in fungi. Both classes have been found widely in other eukaryotes and in bacteria. The two classes are often present together in the same organism. Plants and algae have plastidal aldolase, sometimes a relic of endosymbiosis, in addition to the usual cytosolic aldolase. A bifunctional fructose-bisphosphate aldolase/phosphatase, with class I mechanism, has been found widely in archaea and in some bacteria.[3] The active site of this archaeal aldolase is also in a TIM barrel.

In gluconeogenesis and glycolysis

Gluconeogenesis and glycolysis share a series of six reversible reactions. In gluconeogenesis glyceraldehyde-3-phosphate is reduced to fructose 1,6-bisphosphate with aldolase. In glycolysis fructose 1,6-bisphosphate is made into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate through the use of aldolase. The aldolase used in gluconeogenesis and glycolysis is a cytoplasmic protein.

Three forms of class I protein are found in vertebrates. Aldolase A is preferentially expressed in muscle and brain; aldolase B in liver, kidney, and in enterocytes; and aldolase C in brain. Aldolases A and C are mainly involved in glycolysis, while aldolase B is involved in both glycolysis and gluconeogenesis.[4] Some defects in aldolase B cause hereditary fructose intolerance. The metabolism of free fructose in liver exploits the ability of aldolase B to use fructose 1-phosphate as a substrate.[5] Archaeal fructose-bisphosphate aldolase/phosphatase is presumably involved in gluconeogenesis because its product is fructose 6-phosphate.[6]

In the Calvin cycle

The Calvin cycle is a carbon fixation pathway; it is part of photosynthesis, which convert carbon dioxide and other compounds into glucose. It and gluconeogenesis share a series of four reversible reactions. In both pathways 3-phosphoglycerate (3-PGA or 3-PG) is reduced to fructose 1,6-bisphosphate with aldolase catalyzing the last reaction. A fifth reaction, catalyzed in both pathways by fructose 1,6-bisphosphatase, hydrolyzes the fructose 1-6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The large decrease in free energy makes this reaction irreversible. In the Calvin cycle aldolase also catalyzes the production of sedoheptulose 1,7-bisphosphate from DHAP and erythrose 4-phosphate. The chief products of the Calvin cycle are triose phosphate (TP), which is a mixture of DHAP and G3P, and fructose 6-phosphate. Both are also needed to regenerate RuBP. The aldolase used by plants and algae in the Calvin cycle is usually a plastid-targeted protein encoded by a nuclear gene.


Aldolase catalyzes

fructose 1,6-bisphosphate ⇌ DHAP + G3P

and also

sedoheptulose 1,7-bisphosphate ⇌ DHAP + erythrose 4-phosphate
fructose 1-phosphate ⇌ DHAP + glyceraldehyde

Aldolase is used in the reversible trunk of gluconeogenesis/glycolysis

2(PEP + NADH + H+ + ATP + H2O) ⇌ fructose 1,6-bisphosphate + 2(NAD+ + ADP + Pi)

Aldolase is also used in the part of the Calvin cycle shared with gluconeogenesis, with the irreversible phosphate hydrolysis at the end catalyzed by fructose 1,6-bisphosphatase

2(3-PG + NADPH + H+ + ATP + H2O) ⇌ fructose 1,6-bisphosphate + 2(NADP+ + ADP + Pi)
fructose 1,6-bisphosphate + H2O → fructose 6-phosphate + Pi

In gluconeogenesis 3-PG is produced by enolase and phosphoglycerate mutase acting in series

PEP + H2O ⇌ 2-PG ⇌ 3-PG

In the Calvin cycle 3-PG is produced by rubisco

RuBP + CO2 + H2O → 2(3-PG)

G3P is produced by phosphoglycerate kinase acting in series with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in gluconeogenesis, and in series with glyceraldehyde-3-phosphate dehydrogenase (NADP+) (phosphorylating) in the Calvin cycle

3-PG + ATP ⇌ 1,3-bisphosphoglycerate + ADP
1,3-bisphosphoglycerate + NAD(P)H + H+ ⇌ G3P + Pi + NAD(P)+

Triose-phosphate isomerase maintains DHAP and G3P in near equilibrium, producing the mixture called triose phosphate (TP)


Thus both DHAP and G3P are available to aldolase.

Moonlighting properties

Aldolase has also been implicated in many "moonlighting" or non-catalytic functions, based upon its binding affinity for multiple other proteins including F-actin, α-tubulin, light chain dynein, WASP, Band 3 anion exchanger, phospholipase D (PLD2), glucose transporter GLUT4, inositol trisphosphate, V-ATPase and ARNO (a guanine nucleotide exchange factor of ARF6). These associations are thought to be predominantly involved in cellular structure, however, involvement in endocytosis, parasite invasion, cytoskeleton rearrangement, cell motility, membrane protein trafficking and recycling, signal transduction and tissue compartmentalization have been explored.[7][8][9]


  1. ^ Zgiby SM, Thomson GJ, Qamar S, Berry A (2000). "Exploring substrate binding and discrimination in fructose1, 6-bisphosphate and tagatose 1,6-bisphosphate aldolases". Eur. J. Biochem. 267 (6): 1858–68. doi:10.1046/j.1432-1327.2000.01191.x. PMID 10712619.
  2. ^ Patron NJ, Rogers MB, Keeling PJ (2004). "Gene replacement of fructose-1,6-bisphosphate aldolase supports the hypothesis of a single photosynthetic ancestor of chromalveolates". Eukaryotic Cell. 3 (5): 1169–75. doi:10.1128/EC.3.5.1169-1175.2004. PMC 522617. PMID 15470245.
  3. ^ Siebers B, Brinkmann H, Dörr C, Tjaden B, Lilie H, van der Oost J, Verhees CH (2001). "Archaeal fructose-1,6-bisphosphate aldolases constitute a new family of archaeal type class I aldolase". J. Biol. Chem. 276 (31): 28710–8. doi:10.1074/jbc.M103447200. PMID 11387336.
  4. ^ Walther EU, Dichgans M, Maricich SM, Romito RR, Yang F, Dziennis S, Zackson S, Hawkes R, Herrup K (1998). "Genomic sequences of aldolase C (Zebrin II) direct lacZ expression exclusively in non-neuronal cells of transgenic mice". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2615–20. doi:10.1073/pnas.95.5.2615. PMC 19434. PMID 9482935.
  5. ^ Gopher A, Vaisman N, Mandel H, Lapidot A (1990). "Determination of fructose metabolic pathways in normal and fructose-intolerant children: a C-13 NMR study using C-13 fructose". Proc. Natl. Acad. Sci. U.S.A. 87 (14): 5449–53. doi:10.1073/pnas.87.14.5449. PMC 54342. PMID 2371280.
  6. ^ Estelmann S, Hügler M, Eisenreich W, Werner K, Berg IA, Ramos-Vera WH, Say RF, Kockelkorn D, Gad'on N, Fuchs G (2011). "Labeling and enzyme studies of the central carbon metabolism in Metallosphaera sedula". J. Bacteriol. 193 (5): 1191–200. doi:10.1128/JB.01155-10. PMC 3067578. PMID 21169486.
  7. ^ Rangarajan ES, Park H, Fortin E, Sygusch J, Izard T (2010). "Mechanism of Alolase Control of Sorting Nexin 9 Function in Endocytosis". J. Biol. Chem. 285 (16): 11983–90. doi:10.1074/jbc.M109.092049. PMC 2852936. PMID 20129922.
  8. ^ Ahn AH, Dziennis S, Hawkes R, Herrup K (1994). "The cloning of zebrin II reveals its identity with aldolase C". Development. 120 (8): 2081–90. PMID 7925012.
  9. ^ Merkulova M, Hurtado-Lorenzo A, Hosokawa H, Zhuang Z, Brown D, Ausiello DA, Marshansky V (2011). "Aldolase directly interacts with ARNO and modulates cell morphology and acid vesicle distribution". Am J Physiol Cell Physiol. 300 (6): C1442–55. doi:10.1152/ajpcell.00076.2010. PMC 3118619. PMID 21307348.

Further reading

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Fructose-bisphosphate aldolase class-II Provide feedback

No Pfam abstract.

Literature references

  1. Blom NS, Tetreault S, Coulombe R, Sygusch J; , Nat Struct Biol 1996;3:856-862.: Novel active site in Escherichia coli fructose 1,6-bisphosphate aldolase. PUBMED:8836102 EPMC:8836102

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000771

Class-II aldolases [ PUBMED:1412694 ], mainly found in prokaryotes and fungi, are homodimeric enzymes, which require a divalent metal ion, generally zinc, for their activity. They include fructose-bisphosphate aldolase [ PUBMED:2199259 , PUBMED:1412694 ], a glycolytic enzyme that catalyses the reversible aldol cleavage or condensation of fructose-1,6-bisphosphate into dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate. The family also includes the Escherichia coli galactitol operon protein, gatY, which catalyses the transformation of tagatose 1,6-bisphosphate into glycerone phosphate and D-glyceraldehyde 3-phosphate; and E. coli N-acetyl galactosamine operon protein, agaY, which catalyses the same reaction. There are two histidine residues in the first half of the sequence of these enzymes that have been shown to be involved in binding a zinc ion [ PUBMED:8436219 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A
Number in seed: 689
Number in full: 11877
Average length of the domain: 298.80 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 89.14 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.5 25.5
Trusted cut-off 25.8 25.6
Noise cut-off 25.1 24.5
Model length: 280
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the F_bP_aldolase domain has been found. There are 127 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...