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525  structures 8028  species 0  interactions 27423  sequences 198  architectures

Family: Iso_dh (PF00180)

Summary: Isocitrate/isopropylmalate dehydrogenase

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This is the Wikipedia entry entitled "Isocitrate/isopropylmalate dehydrogenase family". More...

Isocitrate/isopropylmalate dehydrogenase family Edit Wikipedia article

Isocitrate/isopropylmalate dehydrogenase
PDB 1cw4 EBI.jpg
crystal structure of k230m isocitrate dehydrogenase in complex with alpha-ketoglutarate
Identifiers
Symbol Iso_dh
Pfam PF00180
Pfam clan CL0270
InterPro IPR001804
PROSITE PDOC00389
SCOP 1hex
SUPERFAMILY 1hex

In molecular biology, the isocitrate/isopropylmalate dehydrogenase family is a protein family consisting of the evolutionary related enzymes isocitrate dehydrogenase, 3-isopropylmalate dehydrogenase and tartrate dehydrogenase.[1][2][3][4]

Isocitrate dehydrogenase (IDH), is an important enzyme of carbohydrate metabolism which catalyses the oxidative decarboxylation of isocitrate into alpha-ketoglutarate.[1][5] IDH is either dependent on NAD+ EC 1.1.1.41 or on NADP+ EC 1.1.1.42. In eukaryotes there are at least three isozymes of IDH: two are located in the mitochondrial matrix (one NAD+-dependent, the other NADP+-dependent), while the third one (also NADP+-dependent) is cytoplasmic. In Escherichia coli the activity of a NADP+-dependent form of the enzyme is controlled by the phosphorylation of a serine residue; the phosphorylated form of IDH is completely inactivated.

3-isopropylmalate dehydrogenase EC 1.1.1.85 (IMDH) catalyses the third step in the biosynthesis of leucine in bacteria and fungi, the oxidative decarboxylation of 3-isopropylmalate into 2-oxo-4-methylvalerate.[2][3]

Tartrate dehydrogenase EC 1.1.1.93 catalyses the reduction of tartrate to oxaloglycolate.[4]

References

  1. ^ a b Hurley JH, Thorsness PE, Ramalingam V, Helmers NH, Koshland DE, Stroud RM (November 1989). "Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8635–9. doi:10.1073/pnas.86.22.8635. PMC 298342Freely accessible. PMID 2682654. 
  2. ^ a b Imada K, Sato M, Tanaka N, Katsube Y, Matsuura Y, Oshima T (December 1991). "Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution". J. Mol. Biol. 222 (3): 725–38. doi:10.1016/0022-2836(91)90508-4. PMID 1748999. 
  3. ^ a b Zhang T, Koshland DE (January 1995). "Modeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase". Protein Sci. 4 (1): 84–92. doi:10.1002/pro.5560040111. PMC 2142962Freely accessible. PMID 7773180. 
  4. ^ a b Tipton PA, Beecher BS (August 1994). "Tartrate dehydrogenase, a new member of the family of metal-dependent decarboxylating R-hydroxyacid dehydrogenases". Arch. Biochem. Biophys. 313 (1): 15–21. doi:10.1006/abbi.1994.1352. PMID 8053675. 
  5. ^ Cupp JR, McAlister-Henn L (November 1991). "NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae". J. Biol. Chem. 266 (33): 22199–205. PMID 1939242. 

This article incorporates text from the public domain Pfam and InterPro IPR001804

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

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR024084

This entry represents a structural domain found in all types of isocitrate dehydrogenase, and in isopropylmalate dehydrogenase and tartrate dehydrogenase. The crystal structure of Escherichia coli isopropylmalate dehydrogenase has been described [ PUBMED:9086278 ].

The isocitrate and isopropylmalate dehydrogenases family includes isocitrate dehydrogenase (IDH), 3-isopropylmalate dehydrogenase (IMDH) and tartrate dehydrogenase.

IDH is an important enzyme of carbohydrate metabolism which catalyses the oxidative decarboxylation of isocitrate into alpha-ketoglutarate [ PUBMED:2682654 , PUBMED:1939242 ]. IDH is either dependent on NAD + ( EC ) or on NADP + ( EC ). In eukaryotes there are at least three isozymes of IDH: two are located in the mitochondrial matrix (one NAD + -dependent, the other NADP + -dependent), while the third one (also NADP + -dependent) is cytoplasmic. In Escherichia coli, the activity of a NADP + -dependent form of the enzyme is controlled by the phosphorylation of a serine residue; the phosphorylated form of IDH is completely inactivated.

IMDH ( EC ) catalyses the third step in the biosynthesis of leucine in bacteria and fungi, the oxidative decarboxylation of 3-isopropylmalate into 2-oxo-4-methylvalerate [ PUBMED:1748999 , PUBMED:7773180 ].

Tartrate dehydrogenase ( EC ) shows strong homology to prokaryotic isopropylmalate dehydrogenases and, to a lesser extent, isocitrate dehydrogenase [ PUBMED:8053675 ]. It catalyses the reduction of tartrate to oxaloglycolate [ PUBMED:8053675 ].

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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Pfam Clan

This family is a member of clan Iso_DH (CL0270), which has the following description:

This superfamily of enzymes form dimers and have an active site between the two halves.

The clan contains the following 5 members:

FA_synthesis IDH Iso_dh PdxA PTA_PTB

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
(19)
Full
(27423)
Representative proteomes UniProt
(107423)
RP15
(3980)
RP35
(12836)
RP55
(25185)
RP75
(40969)
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PP/heatmap 1            

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

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

Format an alignment

  Seed
(19)
Full
(27423)
Representative proteomes UniProt
(107423)
RP15
(3980)
RP35
(12836)
RP55
(25185)
RP75
(40969)
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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
(19)
Full
(27423)
Representative proteomes UniProt
(107423)
RP15
(3980)
RP35
(12836)
RP55
(25185)
RP75
(40969)
Raw Stockholm Download   Download   Download   Download   Download   Download    
Gzipped 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: isodh;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 19
Number in full: 27423
Average length of the domain: 337.30 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 90.41 %

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 20.1 20.1
Trusted cut-off 20.1 20.1
Noise cut-off 20.0 20.0
Model length: 347
Family (HMM) version: 22
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 Iso_dh domain has been found. There are 525 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
A0A0P0W1E6 View 3D Structure Click here
A0A0R0EGP0 View 3D Structure Click here
A0A0R0IMT3 View 3D Structure Click here
A0A0R0IMT3 View 3D Structure Click here
A0A1D6E501 View 3D Structure Click here
A0A1D6E6B4 View 3D Structure Click here
A0A1D6HC33 View 3D Structure Click here
A0A1D6IF72 View 3D Structure Click here
A0A1D6JZ46 View 3D Structure Click here
A0A1D6JZ46 View 3D Structure Click here
A0A1D6JZ46 View 3D Structure Click here
A0A1D6P1U9 View 3D Structure Click here
A0A1D6Q461 View 3D Structure Click here
A0A1D6Q462 View 3D Structure Click here
A0A1D8PEM5 View 3D Structure Click here
A0A1D8PGS5 View 3D Structure Click here
A0A1D8PHH7 View 3D Structure Click here
A0A1D8PQK5 View 3D Structure Click here
A0A1D8PS79 View 3D Structure Click here
A0A1P8AT86 View 3D Structure Click here
A0A2R8QPC9 View 3D Structure Click here
A0A2R8S0K0 View 3D Structure Click here
A1ZAD2 View 3D Structure Click here
A4HUD9 View 3D Structure Click here
A4I994 View 3D Structure Click here
B0UXL2 View 3D Structure Click here
B4FAD4 View 3D Structure Click here
B4FID6 View 3D Structure Click here
B4FLJ3 View 3D Structure Click here
B6THR9 View 3D Structure Click here
B6TJM1 View 3D Structure Click here
B7Z0E0 View 3D Structure Click here
C0PD27 View 3D Structure Click here
C6T857 View 3D Structure Click here
E7F4R9 View 3D Structure Click here
F1QZA4 View 3D Structure Click here
H9G2T4 View 3D Structure Click here
I1JCB1 View 3D Structure Click here
I1K1I6 View 3D Structure Click here
I1L903 View 3D Structure Click here
I1LI32 View 3D Structure Click here
I1LI93 View 3D Structure Click here
I1LZ93 View 3D Structure Click here
I1M5X1 View 3D Structure Click here
I1M643 View 3D Structure Click here
I1MCD0 View 3D Structure Click here
I1MJH1 View 3D Structure Click here
I1MMY0 View 3D Structure Click here
K7V067 View 3D Structure Click here
O13696 View 3D Structure Click here
O14104 View 3D Structure Click here
O14254 View 3D Structure Click here
O17643 View 3D Structure Click here
O43837 View 3D Structure Click here
O75874 View 3D Structure Click here
O81796 View 3D Structure Click here
O88844 View 3D Structure Click here
P04173 View 3D Structure Click here
P08200 View 3D Structure Click here
P18869 View 3D Structure Click here
P21954 View 3D Structure Click here
P28241 View 3D Structure Click here
P28834 View 3D Structure Click here
P30125 View 3D Structure Click here
P40495 View 3D Structure Click here
P41562 View 3D Structure Click here
P41565 View 3D Structure Click here
P41939 View 3D Structure Click here
P48735 View 3D Structure Click here
P50213 View 3D Structure Click here
P51553 View 3D Structure Click here
P53982 View 3D Structure Click here
P54071 View 3D Structure Click here
P56574 View 3D Structure Click here
P70404 View 3D Structure Click here
P76251 View 3D Structure Click here
P93032 View 3D Structure Click here
P93832 View 3D Structure Click here
P9WKK9 View 3D Structure Click here
P9WKL1 View 3D Structure Click here
Q06197 View 3D Structure Click here
Q0JBV4 View 3D Structure Click here
Q20049 View 3D Structure Click here
Q2FWK2 View 3D Structure Click here
Q2FXN4 View 3D Structure Click here
Q33E21 View 3D Structure Click here
Q4DG65 View 3D Structure Click here
Q4E4L7 View 3D Structure Click here
Q4QQT5 View 3D Structure Click here
Q54B68 View 3D Structure Click here
Q55BI2 View 3D Structure Click here
Q58130 View 3D Structure Click here
Q58991 View 3D Structure Click here
Q5A9D9 View 3D Structure Click here
Q65XK3 View 3D Structure Click here
Q68FX0 View 3D Structure Click here
Q6NV33 View 3D Structure Click here
Q6ZI55 View 3D Structure Click here
Q75JR2 View 3D Structure Click here
Q75JR3 View 3D Structure Click here
Q7F280 View 3D Structure Click here
Q8BPC6 View 3D Structure Click here
Q8I6T2 View 3D Structure Click here
Q8LFC0 View 3D Structure Click here
Q8LG77 View 3D Structure Click here
Q8LPJ5 View 3D Structure Click here
Q8MT18 View 3D Structure Click here
Q8T0R3 View 3D Structure Click here
Q91VA7 View 3D Structure Click here
Q93353 View 3D Structure Click here
Q93714 View 3D Structure Click here
Q945K7 View 3D Structure Click here
Q95YD8 View 3D Structure Click here
Q99NA5 View 3D Structure Click here
Q9D6R2 View 3D Structure Click here
Q9FMT1 View 3D Structure Click here
Q9LQK9 View 3D Structure Click here
Q9LQK9 View 3D Structure Click here
Q9SA14 View 3D Structure Click here
Q9SDG5 View 3D Structure Click here
Q9SLK0 View 3D Structure Click here
Q9SRZ6 View 3D Structure Click here
Q9USP8 View 3D Structure Click here
Q9VD58 View 3D Structure Click here
Q9VWH4 View 3D Structure Click here
Q9W172 View 3D Structure Click here
Q9XHX4 View 3D Structure Click here