Aco1 aconitase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Aco1provided by MGI
Official Full Name: aconitase 1provided by MGI
Primary source: MGI:MGI:87879
See related: Ensembl:ENSMUSG00000028405 AllianceGenome:MGI:87879
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Irp1; Aco-1; Irebp
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. Disruption of this gene is associated with pulmonary hypertension and polycythemia. [provided by RefSeq, Jan 2014]
Expression: Ubiquitous expression in kidney adult (RPKM 60.7), genital fat pad adult (RPKM 48.3) and 27 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 A5; 4 20.24 cM

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (40143429..40199011)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (40143265..40199009)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

H2S regulation of iron homeostasis by IRP1 improves vascular smooth muscle cell functions.
Title: H(2)S regulation of iron homeostasis by IRP1 improves vascular smooth muscle cell functions.
IL-6 likely up-regulates IRP1 and DMT1 expression and down-regulates FPN1 expression in BV2 microglial cells through JNK signaling pathways
Title: Interleukin-6 regulates iron-related proteins through c-Jun N-terminal kinase activation in BV2 microglial cell lines.
Using whole RNA sequencing of bone marrow cells in iron-overloaded mice, it was observed that Idh1 and Aco1, enzymes involved in the TCA cycle, were elevated.
Title: Iron-induced epigenetic abnormalities of mouse bone marrow through aberrant activation of aconitase and isocitrate dehydrogenase.
The Irp1-/- mice develop polycythemia and pulmonary hypertension, and suggesting that Irp1 plays an essential role in erythropoiesis and in the pulmonary and cardiovascular systems.
Title: Iron misregulation and neurodegenerative disease in mouse models that lack iron regulatory proteins.
IRP1 and IRP2 mutant mice rapidly succumb to systemic infection with Salmonella Typhimurium, a pathogenic bacterium that multiplies within macrophages, with increased bacterial burdens in liver and spleen.
Title: Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection.
results uncover an unexpected protective role of IRP1 in pathological conditions associated with altered Fe-S metabolism
Title: Iron regulatory protein 1 sustains mitochondrial iron loading and function in frataxin deficiency.
Aco1 KD in fully differentiated 3T3-L1 adipocytes decreased lipogenic, Idh1, Adipoq, and Glut4 gene expression.
Title: Cytosolic aconitase activity sustains adipogenic capacity of adipose tissue connecting iron metabolism and adipogenesis.
impaired mitochondrial [Fe-S] cluster biogenesis in Mfrn1(gt/gt) cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation and protoporphyrin accumulation
Title: Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria.
Data indicate that JTR-009, a benzimidazole, operated by preventing iron-regulatory protein-1 (IRP1) from binding to the iron-responsive element (IRE) in APP mRNA.
Title: Novel 5' untranslated region directed blockers of iron-regulatory protein-1 dependent amyloid precursor protein translation: implications for down syndrome and Alzheimer's disease.
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.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (4) 1 citation
Endonuclease-mediated (6)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI256519 (e-PCR)
- UniSTS:178981

Aco1 (e-PCR), detects polymorphism
- UniSTS:506702

X61147 (e-PCR)
- UniSTS:125821

Gene Ontology Provided by MGI

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	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	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info
enables iron-sulfur cluster binding	ISO Inferred from Sequence Orthology more info
enables lyase activity	IEA Inferred from Electronic Annotation more info
enables mRNA 5'-UTR binding	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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within intestinal absorption	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within intracellular iron ion homeostasis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within intracellular iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular iron ion homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within post-embryonic development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to iron(II) ion	ISO Inferred from Sequence Orthology more info
involved_in tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor 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; citrate hydro-lyase; cytoplasmic aconitase; iron regulatory protein 1; iron-responsive element-binding protein 1

NP_001406881.1

EC 4.2.1.3

NP_031412.2

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_001419952.1 → NP_001406881.1 cytoplasmic aconitate hydratase

Status: VALIDATED

Source sequence(s)

AL831793

UniProtKB/Swiss-Prot

P28271, Q3TQ15, Q99K54
NM_007386.3 → NP_031412.2 cytoplasmic aconitate hydratase

See identical proteins and their annotated locations for NP_031412.2

Status: VALIDATED

Source sequence(s)

AL831793

Consensus CDS

CCDS18042.1

UniProtKB/Swiss-Prot

P28271, Q3TQ15, Q99K54

UniProtKB/TrEMBL

Q8VDC3

Related

ENSMUSP00000100038.4, ENSMUST00000102973.4

Conserved Domains (1) summary

PTZ00092
Location:3 → 889

PTZ00092; aconitate hydratase-like protein; Provisional