Aco1 aconitase 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Aco1provided by RGD
Official Full Name: aconitase 1provided by RGD
Primary source: RGD:2019
See related: EnsemblRapid:ENSRNOG00000005849 AllianceGenome:RGD:2019
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: AH; IRP1; Acon1
Summary: This gene encodes a member of the aconitase/IPM isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Depending on iron levels in the cytosol, the encoded protein can function as either an aconitase enzyme or as an mRNA binding protein. When cellular iron levels are high, the encoded protein functions as an aconitase, an essential enzyme in the TCA cycle that catalyzes the conversion of citrate to isocitrate. When cellular iron levels are low, the encoded protein regulates iron uptake and utilization by binding to iron-responsive elements in the untranslated regions of mRNAs for genes involved in iron metabolism [provided by RefSeq, Jan 2014]
Expression: Biased expression in Kidney (RPKM 982.0), Liver (RPKM 384.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 5; 5q22

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	5	NC_086023.1 (60055895..60111920)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	5	NC_051340.1 (55259841..55315872)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	5	NC_005104.4 (56425076..56481218)

Chromosome 5 - NC_086023.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Proteomic analysis revealed that the expression levels of two mitochondrial proteins, cytochrome bc1 complex2 (UQCRC2, the major component of electron transport chain complex III) and aconitase (an enzyme involved in the tricarboxylic acid cycle), were decreased by homocysteine in neural stem cells
Title: Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III.
Iron increases turnover of IRP-1 in kidney cells, while increasing aconitase activity, suggesting that the apoprotein (aconitase-inactive) form is not exclusively responsible for turnover.
Title: Iron-dependent turnover of IRP-1/c-aconitase in kidney cells.
These results indicate that aconitase can exert control over respiration (with tissue specificity) and support the hypothesis that inactivation of aconitase may provide a control mechanism to prevent O2(-) and H2O2 formation by the respiratory chain.
Title: Metabolic control analysis of mitochondrial aconitase: influence over respiration and mitochondrial superoxide and hydrogen peroxide production.
Polymer-dependent translocation of IRP-1 in Cd(2+)-exposed cells may underlie effects of Cd(2+) on iron homeostasis.
Title: Cadmium-induced aggregation of iron regulatory protein-1.
Human ACO1 is a moonlighting protein that has both aconitase enzyme activity as well as an mRNA binding function.
Title: The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation.
Results suggest that IL-1beta and TNF-alpha released by microglia might contribute to iron accumulation in ventral mesencephalic neurons by upregulating IRP1 and hepcidin levels through reactive oxygen/nitrogen species production.
Title: Pro-inflammatory cytokines modulate iron regulatory protein 1 expression and iron transportation through reactive oxygen/nitrogen species production in ventral mesencephalic neurons.
Angiotensin receptor blockade recovers hepatic UCP2 expression and aconitase and SDH activities and ameliorates hepatic oxidative damage in insulin resistant rats
Title: Angiotensin receptor blockade recovers hepatic UCP2 expression and aconitase and SDH activities and ameliorates hepatic oxidative damage in insulin resistant rats.
The RNA-binding and aconitase forms of IRP-1 can undergo interconversion dependent on the density of cells growing in culture.
Title: Cell density-dependent shift in activity of iron regulatory protein 1 (IRP-1)/cytosolic (c-)aconitase.
c-aconitase is a critical target involved in the assimilation of Fe and excess dietary Zn can result in negative interactions
Title: Iron dependence and zinc inhibition of duodenal cytosolic aconitase of rat.
The expression of HO1, FTH, and IRP1 mRNAs is higher in the female hippocampus than that observed in male rats.
Title: Regulation of iron-related molecules in the rat hippocampus: sex- and age-associated differences.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH129206 (e-PCR)
- UniSTS:212514

RH129487 (e-PCR)
- UniSTS:212514

RH127730 (e-PCR)
- UniSTS:211040

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables 3 iron, 4 sulfur cluster binding	IBA Inferred from Biological aspect of Ancestor more info
enables 3 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables 3 iron, 4 sulfur cluster binding	ISO Inferred from Sequence Orthology more info
enables 4 iron, 4 sulfur cluster binding	IBA Inferred from Biological aspect of Ancestor more info
enables 4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables 4 iron, 4 sulfur cluster binding	ISO Inferred from Sequence Orthology more info
enables 4 iron, 4 sulfur cluster binding	ISS Inferred from Sequence or Structural Similarity more info
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA binding	ISO Inferred from Sequence Orthology more info
enables aconitate hydratase activity	IBA Inferred from Biological aspect of Ancestor more info
enables aconitate hydratase activity	IDA Inferred from Direct Assay more info	PubMed
enables aconitate hydratase activity	IEA Inferred from Electronic Annotation more info
enables aconitate hydratase activity	ISO Inferred from Sequence Orthology more info
enables aconitate hydratase activity	ISS Inferred from Sequence or Structural Similarity more info
enables iron-responsive element binding	IBA Inferred from Biological aspect of Ancestor more info
enables iron-responsive element binding	IDA Inferred from Direct Assay more info	PubMed
enables iron-responsive element binding	IEA Inferred from Electronic Annotation more info
enables iron-responsive element binding	ISO Inferred from Sequence Orthology more info
enables iron-responsive element binding	ISS Inferred from Sequence or Structural Similarity more info
enables iron-sulfur cluster binding	IDA Inferred from Direct Assay more info	PubMed
enables iron-sulfur cluster binding	ISO Inferred from Sequence Orthology more info
enables mRNA 5'-UTR binding	IDA Inferred from Direct Assay more info	PubMed
enables mRNA regulatory element binding translation repressor activity	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in citrate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in citrate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in citrate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in citrate metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in intestinal absorption	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within intestinal absorption	ISO Inferred from Sequence Orthology more info
involved_in intracellular iron ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular iron ion homeostasis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within intracellular iron ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in liver development	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in post-embryonic development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within post-embryonic development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in regulation of translation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in response to iron(II) ion	IEA Inferred from Electronic Annotation more info
involved_in response to iron(II) ion	ISO Inferred from Sequence Orthology more info
involved_in response to iron(II) ion	ISS Inferred from Sequence or Structural Similarity more info
involved_in tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: cytoplasmic aconitate hydratase

Names: IRE-BP 1; aconitase 1, soluble; citrate hydro-lyase; iron regulatory protein 1; iron-responsive element-binding protein 1

NP_059017.2

EC 4.2.1.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_017321.2 → NP_059017.2 cytoplasmic aconitate hydratase

Status: VALIDATED

Source sequence(s)

JAXUCZ010000005

UniProtKB/Swiss-Prot

Q63270

UniProtKB/TrEMBL

A6IIQ7

Related

ENSRNOP00000078636.2, ENSRNOT00000100040.2

Conserved Domains (1) summary

PTZ00092
Location:3 → 889

PTZ00092; aconitate hydratase-like protein; Provisional