Protein Domain : IPR015934

Type:  Family Name:  Aconitase/2-methylisocitrate dehydratase
Description:  Aconitase (aconitate hydratase; ) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [, ]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is small than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) []. Below is a description of some of the multi-functional activities associated with different aconitases.Eukaryotic mAcn catalyses the second step of the mitochondrial TCA cycle, which is important for energy production, providing high energy electrons in the form of NADH and FADH2 to the mitochondrial oxidative phosphorylation pathway []. The TCA cycle also provides precursors for haem and amino acid production. This enzyme has a second, non-catalytic but essential role in mitochondrial DNA (mtDNA) maintenance: mAcn acts to stabilise mtDNA, forming part of mtDNA protein-DNA complexes known as nucleoids. mAcn is thought to reversibly model nucleoids to directly influence mitochondrial gene expression in response to changes in the cellular environment. Therefore, mAcn can influence the expression of components of the oxidative phosphorylation pathway encoded in mtDNA. Eukaryotic cAcn enzyme balances the amount of citrate and isocitrate in the cytoplasm, which in turn creates a balance between the amount of NADPH generated from isocitrate by isocitrate dehydrogenase with the amount of acetyl-CoA generated from citrate by citrate lyase. Fatty acid synthesis requires both NADPH and acetyl-CoA, as do other metabolic processes, including the need for NADPH to combat oxidative stress. The enzymatic form of cAcn predominates when iron levels are normal, but if they drop sufficiently to cause the disassembly of the [4Fe-4S]-cluster, then cAcn undergoes a conformational change from a compact enzyme to a more open L-shaped protein known as iron regulatory protein 1 (IRP1; or IRE-binding protein 1, IREBP1) [, ]. As IRP1, the catalytic site and the [4Fe-4S]-cluster are lost, and two new RNA-binding sites appear. IRP1 functions in the post-transcriptional regulation of genes involved in iron metabolism - it binds to mRNA iron-responsive elements (IRE), 30-nucleotide stem-loop structures at the 3' or 5' end of specific transcripts. Transcripts containing an IRE include ferritin L and H subunits (iron storage), transferrin (iron plasma chaperone), transferrin receptor (iron uptake into cells), ferroportin (iron exporter), mAcn, succinate dehydrogenase, erythroid aminolevulinic acid synthetase (tetrapyrrole biosynthesis), among others. If the IRE is in the 5'-UTR of the transcript (e.g. in ferritin mRNA), then IRP1-binding prevents its translation by blocking the transcript from binding to the ribosome. If the IRE is in the 3'-UTR of the transcript (e.g. transferrin receptor), then IRP1-binding protects it from endonuclease degradation, thereby prolonging the half-life of the transcript and enabling it to be translated [].IRP2 is another IRE-binding protein that binds to the same transcripts as IRP1. However, since IRP1 is predominantly in the enzymatic cAcn form, it is IRP2 that acts as the major metabolic regulator that maintains iron homeostasis []. Although IRP2 is homologous to IRP1, IRP2 lacks aconitase activity, and is known only to have a single function in the post-transcriptional regulation of iron metabolism genes []. In iron-replete cells, IRP2 activity is regulated primarily by iron-dependent degradation through the ubiquitin-proteasomal system.Bacterial AcnB is also known to be multi-functional. In addition to its role in the TCA cycle, AcnB was shown to be a post-transcriptional regulator of gene expression in Escherichia coliand Salmonella enterica[, ]. In S. enterica, AcnB initiates a regulatory cascade controlling flagella biosynthesis through an interaction with the ftsH transcript, an alternative RNA polymerase sigma factor. This binding lowers the intracellular concentration of FtsH protease, which in turn enhances the amount of RNA polymerase sigma32 factor (normally degraded by FtsH protease), and sigma32 then increases the synthesis of chaperone DnaK, which in turn promotes the synthesis of the flagellar protein FliC. AcnB regulates the synthesis of other proteins as well, such as superoxide dismutase (SodA) and other enzymes involved in oxidative stress.This entry represents several aconitase proteins, including bacterial aconitase A (AcnA), eukaryotic cytosolic aconitase (cAcn) and a few mitochondrial aconitases (mAcn) (but not the majority of mAcn enzymes). This entry also includes a related protein: Fe/S-dependent 2-methylisocitrate dehydratase (AcnD; ). Short Name:  Aconitase/AcnD
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1 Child Features

DB identifier Type Name
IPR012708 Family 2-methylisocitrate dehydratase AcnD, Fe/S-dependent

5 Contains

DB identifier Type Name
IPR015931 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
IPR000573 Domain Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
IPR001030 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
IPR015932 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 2
IPR018136 Binding_site Aconitase family, 4Fe-4S cluster binding site

1 Cross References

Identifier
PTHR11670:SF1

0 Found In

1 GO Annotation

GO Term Gene Name
GO:0008152 IPR015934

1 Ontology Annotations

GO Term Gene Name
GO:0008152 IPR015934

1 Parent Features

DB identifier Type Name
IPR015937 Family Aconitase/isopropylmalate dehydratase

49 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
Traes_3AS_42F2D9445.3 PAC:31811215 Triticum aestivum 253  
Traes_3B_B6A0537FA.10 PAC:32020352 Triticum aestivum 456  
Traes_3B_B6A0537FA.9 PAC:32020350 Triticum aestivum 474  
Traes_3B_B6A0537FA.11 PAC:32020351 Triticum aestivum 456  
Traes_3DS_0A1F1EDD5.9 PAC:31958029 Triticum aestivum 274  
Traes_3DS_0A1F1EDD5.8 PAC:31958028 Triticum aestivum 287  
Traes_3DS_EB1A1B32C.1 PAC:31775831 Triticum aestivum 92  
Traes_7AS_60F755E22.7 PAC:31786298 Triticum aestivum 130  
Pp3c1_670V3.2.p PAC:32967052 Physcomitrium patens 994  
Pp3c1_670V3.3.p PAC:32967053 Physcomitrium patens 994  
Pp3c1_670V3.1.p A0A2K1L6F7 PAC:32967054 Physcomitrium patens 839  
LOC_Os06g19960.1 PAC:33149193 Oryza sativa 696  
Brdisv1pangenome1006526m.p PAC:33623345 Brachypodium distachyon Pangenome 742  
Brdisv1pangenome1008311m.p PAC:33623470 Brachypodium distachyon Pangenome 620  
Brdisv1BdTR11A1048617m.p PAC:35695561 Brachypodium distachyon BdTR11a 800  
Brdisv1BdTR11A1043880m.p PAC:35695354 Brachypodium distachyon BdTR11a 892  
Brdisv1BdTR11A1041355m.p PAC:35696529 Brachypodium distachyon BdTR11a 902  
Brdisv1BdTR11A1041026m.p PAC:35694147 Brachypodium distachyon BdTR11a 874  
Brdisv1BdTR11A1041159m.p PAC:35694805 Brachypodium distachyon BdTR11a 874  
HORVU7Hr1G045470.23 PAC:38548223 Hordeum vulgare 211  
HORVU7Hr1G045470.28 PAC:38548227 Hordeum vulgare 138  
Lsat_1_v5_gn_8_54540.2 PAC:38956539 Lactuca sativa 168  
Zm00001d024952_P015 A0A1D6J331 PAC:40181147 Zea mays 452  
Zm00001d024952_P006 A0A1D6J323 PAC:40181141 Zea mays 789  
Zm00001d024952_P007 A0A1D6J323 PAC:40181142 Zea mays 789  
Zm00001d024952_P011 A0A1D6J327 PAC:40181139 Zea mays 812  
Zm00001d024952_P009 A0A1D6J325 PAC:40181140 Zea mays 798  
Zm00001d004564_P021 A0A1D6EGC3 PAC:40191187 Zea mays 788  
Zm00001d004564_P012 A0A1D6EGB5 PAC:40191185 Zea mays 797  
Zm00001d004564_P020 A0A1D6EGC3 PAC:40191186 Zea mays 788  

11 Publications

First Author Title Year Journal Volume Pages PubMed ID
            9020582
            10087914
            15877277
            16850017
            17513696
            15882410
            15009904
            15543948
            15604397
            16407072
            17185597