Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | the maximal activity requires the presence of sulfhydryl compounds in the medium | Mus musculus | |
additional information | the maximal activity requires the presence of sulfhydryl compounds in the medium | Rattus norvegicus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center | Rattus norvegicus |
additional information | naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center | Mus musculus |
additional information | naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
citrate | citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation | Homo sapiens | |
citrate | citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation | Mus musculus | |
citrate | citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation | Rattus norvegicus | |
fructose-6-phosphate | - |
Homo sapiens | |
fructose-6-phosphate | - |
Mus musculus | |
fructose-6-phosphate | - |
Rattus norvegicus | |
additional information | superoxide inactivates the mRNA-binding activity through direct chemical attack, enzyme competitive inhibition by di- and tricarboxylic acids and inactivation due to modification of cysteine and tyrosine residues, e.g. S-glutathionylation | Homo sapiens | |
additional information | superexpression of mitochondrial ferritin in mouse cells leads to iron deficiency in the cytosol, decrease in the level of cytosolic ferritin, and inhibition of cAH and mAH isozyme activities. Enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues | Mus musculus | |
additional information | enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues; enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues | Rattus norvegicus | |
Oxalomalate | inhibition of the enzyme by oxalomalate reduces glutamate secretion and eliminates the effect of iron ions on the latter | Homo sapiens | |
oxalosuccinate | - |
Homo sapiens | |
oxalosuccinate | - |
Mus musculus | |
oxalosuccinate | - |
Rattus norvegicus | |
peroxynitrite | inactivation due to the release of iron from the Fe-S cluster, other nitric oxide sources decrease the activity of the mitochondrial isozyme | Homo sapiens | |
superoxide anion radical | - |
Mus musculus | |
superoxide anion radical | - |
Rattus norvegicus | |
trans-aconitate | a competitive inhibitor of the enzyme with respect to cis-aconitate and a non-competitive inhibitor with respect to citrate and isocitrate | Homo sapiens | |
Zn2+ | a specific inhibitor of mitochondrial isozyme | Mus musculus | |
Zn2+ | a specific inhibitor of mitochondrial isozyme | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | cytosolic isozyme cAH | Mus musculus | 5829 | - |
cytosol | cytosolic isozyme cAH | Rattus norvegicus | 5829 | - |
cytosol | cytosolic isozyme cAH, IRP1 is a cytosolic isozyme devoid of labile Fe2+ | Homo sapiens | 5829 | - |
cytosol | IRP1 is a cytosolic isozyme devoid of labile Fe2+ | Rattus norvegicus | 5829 | - |
cytosol | IRP1 is a cytosolic isozyme devoid of labile Fe2+ | Mus musculus | 5829 | - |
mitochondrion | mitochondrial isozyme mAH | Mus musculus | 5739 | - |
mitochondrion | mitochondrial isozyme mAH | Rattus norvegicus | 5739 | - |
mitochondrion | mitochondrial isozyme mAH | Homo sapiens | 5739 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | required | Homo sapiens | |
Fe2+ | required, binding structure in the [4Fe-4S] cluster, mechanism of activation of the enzyme by Fe2+, overview | Rattus norvegicus | |
Fe2+ | required, binding structure in the [Fe-S] cluster, mechanism of activation of the enzyme by Fe2+, overview | Mus musculus | |
Fe2+ | required, both isoenzymes have an [4Fe-4S] iron-sulfur cluster bound with cysteine residues Cys437, Cys503, and Cys506, under the action of reductants, the active enzyme form is produced with a complex cation of the [3Fe3S]2+ type, structure, and mechanism of activation of the enzyme by Fe2+, overview | Homo sapiens | |
additional information | IRP1 is a cytosolic isozyme devoid of labile Fe2+ | Rattus norvegicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Rattus norvegicus | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview | ? | - |
? | |
additional information | Rattus norvegicus | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview | ? | - |
? | |
additional information | Mus musculus | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview | ? | - |
? | |
additional information | Homo sapiens | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Blocking of isozyme mAH expression and activity by 40-60% causes a decrease in ATP biosynthesis, increase in citrate secretion, and reduction of the rate of proliferation of human prostate carcinoma cells. extracellular H2O2 strongly induces IRP1 through a signal cascade, introduction of a source of iron ions enhances glutamate secretion in cultivated lens cells and neurons through an increase in cAH activity and intensification of isocitrate formation. The maximal activity requires the presence of sulfhydryl compounds in the medium | ? | - |
? | |
additional information | Homo sapiens | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. A decrease in enzyme activity is observed in some neurodegenerative diseases associated with the development of oxidative stress, in particular, Parkinsons and Alzheimers diseases. Regulation, overview. Extracellular H2O2 strongly induces IRP1 through a signal cascade | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Homo sapiens | P21399 | IRP1 | - |
Mus musculus | - |
- |
- |
Mus musculus | P28271 | - |
- |
Rattus norvegicus | - |
- |
- |
Rattus norvegicus | Q63270 | IRP1 | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | mechanism controlling IRP1 activity at the level of its stability can be phosphorylation of Ser138, Ser138, Ser711, and flanking sequences are highly conserved | Homo sapiens |
Purification (Comment) | Organism |
---|---|
native IRP1 from liver | Rattus norvegicus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
A-549 cell | - |
Homo sapiens | - |
brain | inactive isozyme mAH multimers occur in rat brain in a model of Huntingtons disease | Rattus norvegicus | - |
heart | - |
Homo sapiens | - |
HEK-293 cell | - |
Homo sapiens | - |
hepatoma cell | - |
Mus musculus | - |
kidney | - |
Homo sapiens | - |
liver | - |
Mus musculus | - |
liver | - |
Homo sapiens | - |
liver | - |
Rattus norvegicus | - |
additional information | isozymes cAH and mAH are present in all tissues, and are most active in the heart, kidney, and liver | Homo sapiens | - |
PC-12 cell | - |
Rattus norvegicus | - |
prostate gland | mitochondrial isozyme plays the key role in the bioenergetic theory of malignant transformation of the prostate | Homo sapiens | - |
prostate gland cancer cell line | - |
Homo sapiens | - |
umbilical vein endothelial cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview | Rattus norvegicus | ? | - |
? | |
additional information | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview | Rattus norvegicus | ? | - |
? | |
additional information | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview | Mus musculus | ? | - |
? | |
additional information | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Blocking of isozyme mAH expression and activity by 40-60% causes a decrease in ATP biosynthesis, increase in citrate secretion, and reduction of the rate of proliferation of human prostate carcinoma cells. extracellular H2O2 strongly induces IRP1 through a signal cascade, introduction of a source of iron ions enhances glutamate secretion in cultivated lens cells and neurons through an increase in cAH activity and intensification of isocitrate formation. The maximal activity requires the presence of sulfhydryl compounds in the medium | Homo sapiens | ? | - |
? | |
additional information | role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. A decrease in enzyme activity is observed in some neurodegenerative diseases associated with the development of oxidative stress, in particular, Parkinsons and Alzheimers diseases. Regulation, overview. Extracellular H2O2 strongly induces IRP1 through a signal cascade | Homo sapiens | ? | - |
? | |
additional information | IRP shows RNA-binding activity, which is affected by some hormones and growth factors, e.g. thyroid, erythropoietin, and epidermal growth factor | Rattus norvegicus | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 95000-100000, IRP1, SDS-PAGE | Rattus norvegicus |
More | depending on the conditions, the enzyme can associate to dimer, trimer, and tetramer forms, followed by the loss of enzyme activity | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
aconitase | - |
Mus musculus |
aconitase | - |
Homo sapiens |
aconitase | - |
Rattus norvegicus |
Aconitate hydratase | - |
Mus musculus |
Aconitate hydratase | - |
Homo sapiens |
Aconitate hydratase | - |
Rattus norvegicus |
IRP1 | - |
Rattus norvegicus |
IRP1 | - |
Mus musculus |
IRP1 | - |
Homo sapiens |