ACO1 aconitase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACO1provided by HGNC
Official Full Name: aconitase 1provided by HGNC
Primary source: HGNC:HGNC:117
See related: Ensembl:ENSG00000122729 MIM:100880; AllianceGenome:HGNC:117
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IRP1; ACONS; HEL60; IREB1; IREBP; IREBP1
Summary: The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5' UTR of ferritin mRNA, and in the 3' UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jan 2014]
Expression: Broad expression in fat (RPKM 69.1), kidney (RPKM 53.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p21.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (32384643..32454769)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (32400543..32470694)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (32384641..32454767)

Chromosome 9 - NC_000009.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Iron regulatory protein 1 is required for the propagation of inflammation in inflammatory bowel disease.
Title: Iron regulatory protein 1 is required for the propagation of inflammation in inflammatory bowel disease.
Human IRP1 Translocates to the Nucleus in a Cell-Specific and Iron-Dependent Manner.
Title: Human IRP1 Translocates to the Nucleus in a Cell-Specific and Iron-Dependent Manner.
ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1.
Title: ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1.
The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis.
Title: The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis.
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.
Title: Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.
Cellular iron sensing and regulation: Nuclear IRP1 extends a classic paradigm.
Title: Cellular iron sensing and regulation: Nuclear IRP1 extends a classic paradigm.
HIF-1alpha overexpression enhanced the mRNA levels of TfR1 and DMT1(+IRE), which reversed the inhibition of IRP1 on both.
Title: The roles of hypoxia-inducible Factor-1 and iron regulatory protein 1 in iron uptake induced by acute hypoxia.
These results support the concept that IRP1 is an oxidative stress biosensor that mediates iron accumulation and cell death when deregulated by mitochondrial dysfunction.
Title: Cell death induced by mitochondrial complex I inhibition is mediated by Iron Regulatory Protein 1.
Results indicate that there is a dysregulation of DMT1 + IRE in IA testes, which might due to the up-regulation of IRP1 and HIF-1A.
Title: Pathological changes in Sertoli cells and dysregulation of divalent metal transporter 1 with iron responsive element in the testes of idiopathic azoospermia patients.
Evaluation of the iron regulatory protein-1 interactome has been presented.
Title: Evaluation of the iron regulatory protein-1 interactome.

Submit: New GeneRIF Correction See all GeneRIFs (56)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study to identify genetic determinants of severe asthma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-146792 (e-PCR)
- UniSTS:175433

RH119496 (e-PCR)
- UniSTS:133538

RH70753 (e-PCR)
- UniSTS:6365

D9S1955 (e-PCR)
- UniSTS:12766

Gene Ontology Provided by GOA

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	IMP Inferred from Mutant Phenotype more info	PubMed
enables 4 iron, 4 sulfur cluster binding	IBA Inferred from Biological aspect of Ancestor more info
enables 4 iron, 4 sulfur cluster binding	IDA Inferred from Direct Assay more info	PubMed
enables 4 iron, 4 sulfur cluster binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA binding	NAS Non-traceable Author Statement more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
enables iron-sulfur cluster binding	EXP Inferred from Experiment more info	PubMed
enables mRNA regulatory element binding translation repressor activity	EXP Inferred from Experiment more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in citrate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in citrate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in citrate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intestinal absorption	IEA Inferred from Electronic Annotation more info
involved_in intracellular iron ion homeostasis	TAS Traceable Author Statement more info
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
involved_in response to iron(II) ion	IDA Inferred from Direct Assay more info	PubMed
involved_in tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
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	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: cytoplasmic aconitate hydratase

Names: aconitase 1, soluble; aconitate hydratase, cytoplasmic; citrate hydro-lyase; cytoplasmic aconitase; cytosplasmic aconitase; epididymis luminal protein 60; epididymis secretory sperm binding protein; ferritin repressor protein; iron regulatory protein 1; iron-responsive element-binding protein 1; soluble aconitase

NP_001265281.1

EC 4.2.1.3

NP_001349769.1

EC 4.2.1.3

NP_002188.1

EC 4.2.1.3

XP_047279386.1

EC 4.2.1.3

XP_054218981.1

EC 4.2.1.3

XP_054218982.1

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_001278352.2 → NP_001265281.1 cytoplasmic aconitate hydratase

See identical proteins and their annotated locations for NP_001265281.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

AF261088, AL161783, BC018103, BP287929, DA103947, DA780353

Consensus CDS

CCDS6525.1

UniProtKB/Swiss-Prot

D3DRK7, P21399, Q14652, Q5VZA7

UniProtKB/TrEMBL

Q9HBB2, V9HWB7

Related

ENSP00000438733.2, ENST00000541043.5

Conserved Domains (1) summary

PTZ00092
Location:2 → 889

PTZ00092; aconitate hydratase-like protein; Provisional
NM_001362840.2 → NP_001349769.1 cytoplasmic aconitate hydratase

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

AF261088, AL161783, BC018103, BP287929, DA780353

Consensus CDS

CCDS6525.1

UniProtKB/Swiss-Prot

D3DRK7, P21399, Q14652, Q5VZA7

UniProtKB/TrEMBL

Q9HBB2, V9HWB7

Related

ENSP00000369255.1, ENST00000379923.5

Conserved Domains (1) summary

PTZ00092
Location:2 → 889

PTZ00092; aconitate hydratase-like protein; Provisional
NM_002197.3 → NP_002188.1 cytoplasmic aconitate hydratase

See identical proteins and their annotated locations for NP_002188.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

AL161783, BC018103, DA409113

Consensus CDS

CCDS6525.1

UniProtKB/Swiss-Prot

D3DRK7, P21399, Q14652, Q5VZA7

UniProtKB/TrEMBL

Q9HBB2, V9HWB7

Related

ENSP00000309477.5, ENST00000309951.8

Conserved Domains (1) summary

PTZ00092
Location:2 → 889

PTZ00092; aconitate hydratase-like protein; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

32384643..32454769

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047423430.1 → XP_047279386.1 cytoplasmic aconitate hydratase isoform X1

UniProtKB/TrEMBL

Q9HBB2

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

32400543..32470694

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054363006.1 → XP_054218981.1 cytoplasmic aconitate hydratase isoform X1

UniProtKB/TrEMBL

Q9HBB2
XM_054363007.1 → XP_054218982.1 cytoplasmic aconitate hydratase isoform X2

UniProtKB/Swiss-Prot

D3DRK7, P21399, Q14652, Q5VZA7

UniProtKB/TrEMBL

Q9HBB2, V9HWB7