Summary: Fructose-1-6-bisphosphatase, N-terminal domain
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This is the Wikipedia entry entitled "Fructose 1,6-bisphosphatase". More...
Fructose 1,6-bisphosphatase Edit Wikipedia article
Fructose bisphosphatase is an enzyme in the liver, that converts fructose-1,6-bisphosphate to fructose-6-phosphate in gluconeogenesis (the making of glucose from smaller substrates). Fructose bisphosphatase does the opposite job to phosphofructokinase, and both these enzymes only work in one direction.
Fructose bisphosphatase deficiency
If there is a deficiency in fructose bisphosphatase, gluconeogenesis will not occur correctly. Glycolysis (the break-down of glucose) will still work, as this does not use this enzyme.
Without effective gluconeogenesis (GNG), hypoglycaemia will set in after about 12 hours. This is the time when liver glycogen stores have been exhausted, and the body has to rely on GNG. When given a dose of glucagon (which would normally increase blood glucose) nothing will happen, as stores are depleted and GNG doesn't work. (In fact, the patient would already have high glucagon levels.)
There is no problem with the metabolism of glucose or galactose, but fructose and glycerol cannot be used as fuels. If fructose or glycerol are given, there will be a build up of phophorylated three-carbon sugars. This leads to phosphate depletion within the cells, and also in the blood. Without phosphate, ATP cannot be made, and many cell processes cannot occur.
High levels of glucagon will tend to release fatty acids from adipose tissue, and this will combine with glycerol that cannot be used in the liver, to make triacylglycerides causing a fatty liver.
As three carbon molecules cannot be used to make glucose, the will instead be made into pyruvate and lactate. These acids cause a drop in the pH of the blood (a metabolic acidosis). Acetyl CoA will also build up, leading to the creation of ketone bodies.
To treat people with a deficiency of this enzyme, they must avoid needing gluconeogenesis to make glucose. This can be accomplished by not fasting for long periods, and eating high-carbohydrate food. They should avoid fructose containing foods (as well as sucrose which breaks down to fructose).
As with all single-gene metabolic disorders, there is always hope for genetic therapy, inserting a healthy copy of the gene into the liver.
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Fructose-1-6-bisphosphatase, N-terminal domain Provide feedback
This family represents the N-terminus of this protein family.
Literature references
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Weeks CM, Roszak AW, Erman M, Kaiser R, Jornvall H, Ghosh D; , Acta Crystallogr D Biol Crystallogr 1999;55:93-102.: Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution. PUBMED:10089399 EPMC:10089399
Internal database links
SCOOP: | Inositol_P |
Similarity to PfamA using HHSearch: | Inositol_P |
External database links
HOMSTRAD: | fbpase |
PROSITE: | PDOC00114 |
SCOP: | 1frp |
This tab holds annotation information from the InterPro database.
InterPro entry IPR033391
Fructose-1,6-bisphosphatase (FBPase) is a critical regulatory enzyme in gluconeogenesis that catalyses the removal of 1-phosphate from fructose 1,6-bis-phosphate to form fructose 6-phosphate [ PUBMED:2159755 , PUBMED:3008716 ]. Five different classes (or types) of FBPases have been identified based on their amino acid sequences, with class I most widely distributed among living organisms [ PUBMED:16670087 ].
This entry represents the N terminus of the FBPase class 1 family.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Phospoesterase (CL0171), which has the following description:
Members of this clan show metal-dependent / lithium sensitive phosphomonoesterase activity. The clan includes inositol polyphosphate 1 phosphatase and fructose 1,6-bisphosphatase [1].
The clan contains the following 3 members:
FBPase FBPase_glpX Inositol_PAlignments
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...
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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.
Seed (7) |
Full (6892) |
Representative proteomes | UniProt (23444) |
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RP15 (1167) |
RP35 (3203) |
RP55 (6301) |
RP75 (10184) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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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.
Seed (7) |
Full (6892) |
Representative proteomes | UniProt (23444) |
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RP15 (1167) |
RP35 (3203) |
RP55 (6301) |
RP75 (10184) |
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Raw Stockholm | |||||||
Gzipped |
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...
Trees
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.
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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
Seed source: | Prosite |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Finn RD |
Number in seed: | 7 |
Number in full: | 6892 |
Average length of the domain: | 179.3 aa |
Average identity of full alignment: | 40 % |
Average coverage of the sequence by the domain: | 52.83 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 191 | ||||||||||||
Family (HMM) version: | 23 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
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 FBPase domain has been found. There are 442 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.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.