ACO1
ACO1 (aconitase 1, also known as IRP1, IREBP and IREB1) is a bifunctional cytosolic protein. It acts as an iron-sulfur aconitase when cellular iron is high and as an mRNA-binding regulator of iron metabolism when iron is low. Browse Assay Genie's current range of ACO1 research reagents below, or read on for the biology behind the target.
ACO1 is a cytosolic protein that switches between two mechanistically distinct functions according to cellular iron status. When iron levels are high, the protein binds a 4Fe-4S cluster, which precludes RNA binding and promotes aconitase activity: the isomerisation of citrate to isocitrate via cis-aconitate. In this form it functions as an essential enzyme in the TCA cycle.
When cellular iron levels are low, the protein instead binds iron-responsive elements (IREs), stem-loop structures found in the 5' UTR of ferritin mRNA and in the 3' UTR of transferrin receptor mRNA. Binding to the IRE represses translation of ferritin mRNA and inhibits degradation of the otherwise rapidly degraded transferrin receptor mRNA. In this way the protein helps to control intracellular iron levels. Because it performs these separate functions, it has been identified as a moonlighting protein.
The ACO1 gene encodes a member of the aconitase gene group, and the protein belongs to the aconitase/IPM isomerase family. Alternative splicing results in multiple transcript variants. The protein is also known as IRP1 (iron regulatory protein 1), IREBP and IREB1, and the previous gene name was aconitase 1, soluble. Mouse and rat both carry an orthologous Aco1 gene. Researchers studying the ACO1 protein often work alongside the mitochondrial aconitase, ACO2, to distinguish cytosolic from mitochondrial activity.
ACO1 controls intracellular iron levels by binding iron-responsive elements in ferritin and transferrin receptor mRNAs when iron is low.
IRE binding represses ferritin mRNA translation and protects transferrin receptor mRNA from degradation, making ACO1 a model for RNA-protein regulation.
With a 4Fe-4S cluster, ACO1 catalyses citrate to isocitrate conversion via cis-aconitate, supporting studies of iron-sulfur enzyme function.
ACO1 performs mechanistically distinct functions in one polypeptide, offering a clear example for studying how cofactor state switches protein activity.
ACO1 is a bifunctional cytosolic protein. With a 4Fe-4S cluster, present when iron is high, it works as an aconitase converting citrate to isocitrate. When iron is low it binds iron-responsive elements in ferritin and transferrin receptor mRNAs, regulating their translation and stability.
ACO1 is also called IRP1, IREBP and IREB1, and its UniProt name is cytoplasmic aconitate hydratase. A previous HGNC name was aconitase 1, soluble. Alternative splicing produces multiple transcript variants, so check which isoform is relevant to your work.
Yes. Both mouse and rat have an orthologous gene named Aco1. ACO1 belongs to the aconitase/IPM isomerase family and the HGNC aconitase gene group; check the datasheet of any product for its validated reactivity.
Aconitase paralogues and other enzymes of cellular metabolism with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P21399; product specifications from Assay Genie datasheets.