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578  structures 8830  species 0  interactions 12345  sequences 79  architectures

Family: TIM (PF00121)

Summary: Triosephosphate isomerase

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This is the Wikipedia entry entitled "Triosephosphate isomerase". More...

Triosephosphate isomerase Edit Wikipedia article

(Fig. 1) Ribbon diagram of the catalytic perfect enzyme TIM.

Triose-phosphate isomerase, also called TIM, is an enzyme that catalyzes the reversible isomerisation of D-glyceraldehyde 3-phosphate to dihydroxyacetone phosphate, which are triose-phosphates, hence the name of the enzyme. This reaction is a part of the glucose-metabolism. TIM was found to occur in every organsims in which TIM was looked for, including humans, chicken, the sleeping sickness parasite, and the bacterium E. coli. Furthermore TIM catalyzes this reaction so fast that it an catalytic perfect enzyme.

The three-dimensional structure (Fig. 1) contains on the outside α-helices, and on the inside 8 ß-sheets. This structure is called ß/α-barrel (called alpha-beta barrel) or also TIM-barrel, since TIM is the prototype of this structure. Figure 1 shows one subunit of the dimeric human TIM. The active site of this enzyme is in the middle of this image. The N-terminus of this protein (the beginning of the amino acid chain) is in dark blue, the C-terminus (the end) is in red).

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.

Triosephosphate isomerase Provide feedback

Triosephosphate isomerase ( EC:5.3.1.1) (TIM) [1] is the glycolytic enzyme that catalyses the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. TIM plays an important role in several metabolic pathways and is essential for efficient energy production, present in eukaryotes and prokaryotes. TIM is a dimer of identical subunits, each of which is made up of about 250 amino-acid residues. A glutamic acid residue is involved in the catalytic mechanism [2,3]. The tertiary structure of TIM has eight beta/alpha motifs folded into a barrel structure [4]. The sequence around the active site residue is perfectly conserved in all known TIM's. Deficiencies in TIM are associated with haemolytic anaemia coupled with a progressive, severe neurological disorder [5].

Literature references

  1. Lolis E, Alber T, Davenport RC, Rose D, Hartman FC, Petsko GA;, Biochemistry. 1990;29:6609-6618.: Structure of yeast triosephosphate isomerase at 1.9-A resolution. PUBMED:2204417 EPMC:2204417

  2. Knowles JR;, Nature. 1991;350:121-124.: Enzyme catalysis: not different, just better. PUBMED:2005961 EPMC:2005961

  3. Jogl G, Rozovsky S, McDermott AE, Tong L;, Proc Natl Acad Sci U S A. 2003;100:50-55.: Optimal alignment for enzymatic proton transfer: structure of the Michaelis complex of triosephosphate isomerase at 1.2-A resolution. PUBMED:12509510 EPMC:12509510

  4. Nagano N, Orengo CA, Thornton JM;, J Mol Biol. 2002;321:741-765.: One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions. PUBMED:12206759 EPMC:12206759

  5. Olah J, Orosz F, Keseru GM, Kovari Z, Kovacs J, Hollan S, Ovadi J;, Biochem Soc Trans. 2002;30:30-38.: Triosephosphate isomerase deficiency: a neurodegenerative misfolding disease. PUBMED:12023819 EPMC:12023819


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000652

Triosephosphate isomerase ( EC ) (TIM) [ PUBMED:2204417 ] is the glycolytic enzyme that catalyses the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. TIM plays an important role in several metabolic pathways and is essential for efficient energy production. It is present in eukaryotes as well as in prokaryotes. TIM is a dimer of identical subunits, each of which is made up of about 250 amino-acid residues. A glutamic acid residue is involved in the catalytic mechanism [ PUBMED:2005961 , PUBMED:12509510 ].

The tertiary structure of TIM has eight beta/alpha motifs folded into a barrel structure. The TIM barrel fold occurs ubiquitously and is found in numerous other enzymes that can be involved in energy metabolism, macromolecule metabolism, or small molecule metabolism [ PUBMED:12206759 ].

The sequence around the active site residue is perfectly conserved in all known TIM's. Deficiencies in TIM are associated with haemolytic anaemia coupled with a progressive, severe neurological disorder [ PUBMED:12023819 ].

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...

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Alignments

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
(207)
Full
(12345)
Representative proteomes UniProt
(59422)
RP15
(1989)
RP35
(6166)
RP55
(12031)
RP75
(19788)
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  Seed
(207)
Full
(12345)
Representative proteomes UniProt
(59422)
RP15
(1989)
RP35
(6166)
RP55
(12031)
RP75
(19788)
Alignment:
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  Seed
(207)
Full
(12345)
Representative proteomes UniProt
(59422)
RP15
(1989)
RP35
(6166)
RP55
(12031)
RP75
(19788)
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...

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.

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: Sonnhammer ELL
Number in seed: 207
Number in full: 12345
Average length of the domain: 237.4 aa
Average identity of full alignment: 39 %
Average coverage of the sequence by the domain: 91.55 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.1 20.1
Trusted cut-off 20.1 20.1
Noise cut-off 20.0 19.9
Model length: 245
Family (HMM) version: 21
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 TIM domain has been found. There are 578 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.

Protein Predicted structure External Information
A0A044V7N3 View 3D Structure Click here
A0A077ZC84 View 3D Structure Click here
A0A077ZLG6 View 3D Structure Click here
A0A0D2GJR5 View 3D Structure Click here
A0A0D2GZE9 View 3D Structure Click here
A0A0G2JWU1 View 3D Structure Click here
A0A0H3H4K9 View 3D Structure Click here
A0A0J9YA50 View 3D Structure Click here
A0A0K0E4R7 View 3D Structure Click here
A0A0R0EPH6 View 3D Structure Click here
A0A0R0G6T3 View 3D Structure Click here
A0A144A4G4 View 3D Structure Click here
A0A158Q4N9 View 3D Structure Click here
A0A175VY52 View 3D Structure Click here
A0A175WAP2 View 3D Structure Click here
A0A1C1C9Y2 View 3D Structure Click here
A0A1C1CR41 View 3D Structure Click here
A0A1D6ETY2 View 3D Structure Click here
A0A1D6FVM4 View 3D Structure Click here
A0A1D6K471 View 3D Structure Click here
A0A1D6KAX1 View 3D Structure Click here
A0A1D6KX49 View 3D Structure Click here
A0A1D6MQG5 View 3D Structure Click here
A0A1Q1BV54 View 3D Structure Click here
A0A368UHG1 View 3D Structure Click here
A0A3P7DT41 View 3D Structure Click here
A0L8V0 View 3D Structure Click here
A0PYP2 View 3D Structure Click here
A0R756 View 3D Structure Click here
A1A1N2 View 3D Structure Click here
A1APN8 View 3D Structure Click here
A1AXX3 View 3D Structure Click here
A1BHJ1 View 3D Structure Click here
A1K5A6 View 3D Structure Click here
A1S458 View 3D Structure Click here
A1SWS5 View 3D Structure Click here
A1T8L2 View 3D Structure Click here
A1TLL4 View 3D Structure Click here
A1UFP1 View 3D Structure Click here
A1US90 View 3D Structure Click here