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Information on EC 4.2.1.3 - aconitate hydratase and Organism(s) Mus musculus and UniProt Accession Q99KI0
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4.2.1.3 aconitate hydrataseIUBMB Comments
Besides interconverting citrate and cis-aconitate, it also interconverts cis-aconitate with isocitrate and, hence, interconverts citrate and isocitrate. The equilibrium mixture is 91% citrate, 6% isocitrate and 3% aconitate. cis-Aconitate is used to designate the isomer (Z)-prop-1-ene-1,2,3-tricarboxylate. An iron-sulfur protein, containing a [4Fe-4S] cluster to which the substrate binds.
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Word Map
- 4.2.1.3
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iron-sulfur
- transferrin
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tricarboxylic
- dismutase
- fe-s
- succinate
- tca
- malate
-
citric
- cardiac
-
rna-binding
- neurodegenerative
- frataxin
-
krebs
- fumarase
- friedreich
- heme
- ataxia
- parkinson
- overload
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iron-dependent
- alpha-ketoglutarate
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stem-loops
- fluorocitrate
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bioenergetics
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ferroportin
-
county
- hepcidin
- peroxynitrite
- mnsod
- fluoroacetate
-
georgia
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cluster-containing
-
iron-deficient
- iscu
-
iron-replete
-
iron-induced
-
iron-mediated
- alabama
-
kennedy
-
itaconic
-
ferrochelatase
- cubane
-
desulfurase
-
nadp-isocitrate
-
rna-protein
-
iron-related
-
soxrs
- l-ferritin
- isopropylmalate
- medicine
- environmental protection
- synthesis
- biotechnology
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
aconitase, iron regulatory protein, irp-1, ire-bp, macon, iron regulatory protein 1, aconitate hydratase, cytoplasmic aconitase, aconitase a, c-aconitase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aconitase
Aconitate hydratase
cis-aconitase
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-
-
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citrate hydro-lyase
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-
-
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Ferritin repressor protein
-
-
-
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hydratase, aconitate
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-
-
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IP210
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-
-
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IRE-BP
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-
-
-
Iron regulatory protein
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-
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-
iron-responsive element binding protein
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-
-
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IRP
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-
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IRP1
Major iron-containing protein
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-
-
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MICP
-
-
-
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aconitase
-
-
-
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Aconitate hydratase
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-
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IRP1
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
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-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
citrate(isocitrate) hydro-lyase (cis-aconitate-forming)
Besides interconverting citrate and cis-aconitate, it also interconverts cis-aconitate with isocitrate and, hence, interconverts citrate and isocitrate. The equilibrium mixture is 91% citrate, 6% isocitrate and 3% aconitate. cis-Aconitate is used to designate the isomer (Z)-prop-1-ene-1,2,3-tricarboxylate. An iron-sulfur protein, containing a [4Fe-4S] cluster to which the substrate binds.
CAS REGISTRY NUMBER
COMMENTARY
9024-25-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
iron regulatory protein-1 controls the expression of several mRNAs by binding to iron-responsive elements in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. Iron regulatory protein activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2
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?
additional information
?
-
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview
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-
?
additional information
?
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
iron regulatory protein-1 controls the expression of several mRNAs by binding to iron-responsive elements in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. Iron regulatory protein activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2
-
?
additional information
?
-
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview
-
-
?
additional information
?
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
required, binding structure in the [Fe-S] cluster, mechanism of activation of the enzyme by Fe2+, overview
Iron
-
iron regulatory protein-1 controls the expression of several mRNAs by binding to iron-responsive elements in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. Iron regulatory protein activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
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
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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
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
menadione sodium bisulfite
-
causes a modest activation of IRP-1 to bind to iron resonsive elements within 15-30 min. Menadione-induced oxidative stress leads to post-translational inactivation of both genetic and enzymatic functions of IRP-1 by a mechanism that lies beyond the classical Fe-S cluster switch and exerts multiple effects on cellular iron metabolism
additional information
acetyl-CoA-driven acetylation leads to about 45% activation. The increase in activity is a result of increased maximal velocity
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additional information
-
acetyl-CoA-driven acetylation leads to about 45% activation. The increase in activity is a result of increased maximal velocity
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additional information
-
the maximal activity requires the presence of sulfhydryl compounds in the medium
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additional information
the maximal activity requires the presence of sulfhydryl compounds in the medium
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
repeated contractions increase aconitase activity by 50%. Increase is not accompanied by increase in aconitase protein, but is markedly inhibited by cyclosporin A
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
significant decrease in activity with age, accompanied by relatively subtle alterations in activities of other citric acid cycle enzymes. Changes contribute to a decline in overall efficiency of mitochondrial bioenegetics with age
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an age-related decrease in aconitase activity along with relatively subtle alterations in activities of other citric acid cycle enzymes may contribute to a decline in the overall efficiency of mitochondrial bioenergetics. The maximal activity of aconitase in mitochondria of 16-month-old (118 nmol aconitate/min/mg protein) and 24-month-old (108 nmol/min/mg protein) mice is consistently less than that from 6-month-old (147 aconitate/min/mg protein) mice
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ACON_MOUSE
780
0
85464
Swiss-Prot
Mitochondrion (Reliability: 2)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acetylation
in vitro chemical acetylation with either acetic anhydride or acetyl-CoA results in increased aconitase activity that is reversed with SIRT3 treatment. Lysine residues K31, K138, K144, K401, K549, K689, K700, K701, and K723 represent the most responsive sites. A high fat diet (60% kcal from fat) also shows significantly increased mitochondrial aconitase activity without changes in protein level and produces increased aconitase acetylation at multiple sites
phosphoprotein
-
aconitase is phosphorylated on serine residues. Increase in extensor digitorum longus muscle enzyme activity upon repeated contraction is inhibited by cyclosporin A, an inhibitor of the protein phosphates calcineurin
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular modeling suggests acetylation at K144 may perturb the tertiary structure of the enzyme
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
a high fat diet (60% kcal from fat) shows significantly increased mitochondrial aconitase activity without changes in protein level and produces increased aconitase acetylation at multiple sites
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gehring, N.H.; Hentze, M.W.; Pantopoulos, K.
Inactivation of both RNA binding and aconitase activities of iron regulatory protein-1 by quinone-induced oxidative stress
J. Biol. Chem.
274
6219-6225
1999
Mus musculus
Zhang, S.; Sandstroem, M.E.; Lanner, J.T.; Thorell, A.; Westerblad, H.; Katz, A.
Activation of aconitase in mouse fast-twitch skeletal muscle during contraction-mediated oxidative stress
Am. J. Physiol.
293
C1154-C1159
2007
Homo sapiens, Mus musculus
Yarian, C.S.; Toroser, D.; Sohal, R.S.
Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice
Mech. Ageing Dev.
127
79-84
2006
Mus musculus
Matasova, L.V.; Popova, T.N.
Aconitate hydratase of mammals under oxidative stress
Biochemistry (Moscow)
73
957-964
2008
Homo sapiens, Homo sapiens (P21399), Mus musculus, Mus musculus (P28271), Rattus norvegicus, Rattus norvegicus (Q63270)
Fernandes, J.; Weddle, A.; Kinter, C.S.; Humphries, K.M.; Mather, T.; Szweda, L.I.; Kinter, M.
Lysine acetylation activates mitochondrial aconitase in the heart
Biochemistry
54
4008-4018
2015
Mus musculus (Q99KI0), Mus musculus
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