ACO2 aconitase 2, mitochondrial [Homo sapiens (human)] - Gene

Summary

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Official Symbol: ACO2provided by HGNC
Official Full Name: aconitase 2, mitochondrialprovided by HGNC
Primary source: HGNC:118
Locus tag: RP3-347H13.8
See related: Ensembl:ENSG00000100412; HPRD:00012; MIM:100850; Vega:OTTHUMG00000030544
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: ICRD; ACONM
Summary: The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 22q13.2

Sequence :: Chromosome: 22; NC_000022.10 (41865129..41924993)

See ACO2 in Epigenomics, MapViewer

Chromosome 22 - NC_000022.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Homozygosity mapping followed by whole-exome sequencing disclosed a Ser112Arg mutation in ACO2.
Title: Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2.
these results suggest that p53 downregulation of mACON gene expression in human prostate carcinoma cells may not occur through the putative consensus p53 response elements found within the mACON promoter.
Title: p53 downregulates the gene expression of mitochondrial aconitase in human prostate carcinoma cells.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
abolishes oxidant-induced apoptosis
Title: Role of mitochondrial hOGG1 and aconitase in oxidant-induced lung epithelial cell apoptosis.
This protein has been found differentially expressed in the Wernicke's Area from patients with schizophrenia.
Title: Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation.
This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia.
Title: Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia.
ACO2 is often deleted in colorectal cancer but is unlikely to be the true target of the deletions
Title: Mutation and LOH analysis of ACO2 in colorectal cancer: no evidence of biallelic genetic inactivation.
Manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.
Title: Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells.
Lon protease selectively recognizes and degrades the oxidized, hydrophobic form of aconitase after mild oxidative modification, but that severe oxidation results in aconitase aggregation, which makes it a poor substrate for Lon.
Title: Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism.
The m-aconitase promoter is contained in a 153-bp 5' fragment lacking a TATA or CAAT sequence. Sp1 binding to specific Sp1 site is needed for promoter activity. Other transcription factors are recruited through protein-protein interactions.
Title: Characterization of the mitochondrial aconitase promoter and the identification of transcription factor binding.

Submit: New GeneRIF Correction

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

Infantile cerebellar-retinal degeneration

MIM: 614559

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q99798	Q6EEV6	SUMO4	HPRD	PubMed
BioGRID:106566	BioGRID:115713	ACAA2	BioGRID	PubMed	Co-fractionation
BioGRID:106566	BioGRID:106556	ACAT1	BioGRID	PubMed	Co-fractionation
BioGRID:106566	BioGRID:119127	AK3	BioGRID	PubMed	Co-fractionation
BioGRID:106566	BioGRID:106848	APP	BioGRID	PubMed	Reconstituted Complex
BioGRID:106566	BioGRID:131172	ATXN1L	BioGRID	PubMed	Two-hybrid
BioGRID:106566	BioGRID:108403	ESR1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106566	BioGRID:109883	ITGA4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106566	BioGRID:111683	PSMD4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106566	BioGRID:117439	SIN3A	BioGRID	PubMed	Co-fractionation
BioGRID:106566	BioGRID:117071	SRRM2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106566	BioGRID:132223	SUMO4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106566	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106566	BioGRID:113255	VCAM1	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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2-Oxocarboxylic acid metabolism, organism-specific biosystem (from KEGG)
2-Oxocarboxylic acid metabolism, organism-specific biosystem2-Oxocarboxylic acids are the most elementary set of metabolites that includes pyruvate (2-oxopropanoate), 2-oxobutanoate, oxaloacetate (2-oxobutanedioate) and 2-oxoglutarate. This diagram illustrate...
2-Oxocarboxylic acid metabolism, conserved biosystem (from KEGG)
2-Oxocarboxylic acid metabolism, conserved biosystem2-Oxocarboxylic acids are the most elementary set of metabolites that includes pyruvate (2-oxopropanoate), 2-oxobutanoate, oxaloacetate (2-oxobutanedioate) and 2-oxoglutarate. This diagram illustrate...
Biosynthesis of amino acids, organism-specific biosystem (from KEGG)
Biosynthesis of amino acids, organism-specific biosystem
Biosynthesis of amino acids
Biosynthesis of amino acids, conserved biosystem (from KEGG)
Biosynthesis of amino acids, conserved biosystem
Biosynthesis of amino acids
Citrate cycle (TCA cycle), organism-specific biosystem (from KEGG)
Citrate cycle (TCA cycle), organism-specific biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Citrate cycle (TCA cycle), conserved biosystem (from KEGG)
Citrate cycle (TCA cycle), conserved biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate, organism-specific biosystem (from KEGG)
Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate, conserved biosystem (from KEGG)
Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Citric acid cycle (TCA cycle), organism-specific biosystem (from REACTOME)
Citric acid cycle (TCA cycle), organism-specific biosystemIn the citric acid or tricarboxylic acid (TCA) cycle, the acetyl group of acetyl CoA (derived primarily from oxidative decarboxylation of pyruvate, beta-oxidation of long-chain fatty acids, and catab...
Glyoxylate and dicarboxylate metabolism, organism-specific biosystem (from KEGG)
Glyoxylate and dicarboxylate metabolism, organism-specific biosystem
Glyoxylate and dicarboxylate metabolism
Glyoxylate and dicarboxylate metabolism, conserved biosystem (from KEGG)
Glyoxylate and dicarboxylate metabolism, conserved biosystem
Glyoxylate and dicarboxylate metabolism
Lysine biosynthesis, organism-specific biosystem (from KEGG)
Lysine biosynthesis, organism-specific biosystem
Lysine biosynthesis
Lysine biosynthesis, conserved biosystem (from KEGG)
Lysine biosynthesis, conserved biosystem
Lysine biosynthesis
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Mitochondrial Protein Import, organism-specific biosystem (from REACTOME)
Mitochondrial Protein Import, organism-specific biosystemA human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four lo...
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystem (from REACTOME)
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystemPyruvate metabolism and the citric acid (TCA) cycle together link the processes of energy metabolism in a human cell with one another and with key biosynthetic reactions. Pyruvate, derived from the r...
TCA Cycle, organism-specific biosystem (from WikiPathways)
TCA Cycle, organism-specific biosystemThe [[wikipedia:citric_acid_cycle|citric acid cycle]], also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle, (or rarely, the Szent-Gyorgyi-Krebs cycle) is a series of enzyme-cata...
TCA cycle, organism-specific biosystem (from BIOCYC)
TCA cycle, organism-specific biosystem
TCA cycle
TCA cycle II (eukaryotic), conserved biosystem (from BIOCYC)
TCA cycle II (eukaryotic), conserved biosystemGeneral Background The TCA pathway is a catabolic pathway of aerobic respiration that generates both energy and reducing power. In addition, it is also the first step in generating precursors for bi...
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystem (from REACTOME)
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystemThe metabolism of pyruvate provides one source of acetyl-CoA which enters the citric acid (TCA, tricarboxylic acid) cycle to generate energy and the reducing equivalent NADH. These reducing equivalen...

General gene information

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Markers

RH11380 (e-PCR)
- UniSTS:83991

D22S1253 (e-PCR)
- UniSTS:2853

RH48483 (e-PCR)
- UniSTS:73004

RH47879 (e-PCR)
- UniSTS:82996

D22S678 (e-PCR)
- UniSTS:54164

GDB:451682 (e-PCR)
- UniSTS:157344

A007B26 (e-PCR)
- UniSTS:9892

RH11189 (e-PCR)
- UniSTS:92335

MARC_5597-5598:1044046898:1 (e-PCR)
- UniSTS:269542

D22S998E (e-PCR)
- UniSTS:28909

Homology

Homologs of the ACO2 gene: The ACO2 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, and N.crassa.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
3 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
citrate hydro-lyase (cis-aconitate-forming) activity	IEA Inferred from Electronic Annotation more info
iron ion binding	IDA Inferred from Direct Assay more info	PubMed
isocitrate hydro-lyase (cis-aconitate-forming) activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell death	IEA Inferred from Electronic Annotation more info
citrate metabolic process	IDA Inferred from Direct Assay more info	PubMed
generation of precursor metabolites and energy	TAS Traceable Author Statement more info	PubMed
isocitrate metabolic process	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
tricarboxylic acid cycle	IDA Inferred from Direct Assay more info	PubMed
tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info
tricarboxylic acid cycle	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: aconitate hydratase, mitochondrial

Names: aconitate hydratase, mitochondrial; citrate hydro-lyase

NP_001089.1

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.

Genomic

NG_032143.1 RefSeqGene

Range

5001..64865

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001098.2 → NP_001089.1 aconitate hydratase, mitochondrial precursor

Status: REVIEWED

Source sequence(s)

AA724140, BC014092, BC026196

Consensus CDS

CCDS14017.1

UniProtKB/Swiss-Prot

Q99798

Related

ENSP00000216254, OTTHUMP00000165920, ENST00000216254, OTTHUMT00000259151

Conserved Domains (3) summary

cd01578
Location:587 – 735
Blast Score: 772

AcnA_Mitochon_Swivel; Mitochondrial aconitase A swivel domain. Aconitase (also known as aconitate hydratase and citrate hydro-lyase) catalyzes the reversible isomerization of citrate and isocitrate as part of the TCA cycle. This is the aconitase swivel domain, which undergoes ...

cd01584
Location:95 – 505
Blast Score: 2252

AcnA_Mitochondrial; Aconitase catalyzes the reversible isomerization of citrate and isocitrate as part of the TCA cycle

TIGR01340
Location:45 – 775
Blast Score: 3068

aconitase_mito; aconitate hydratase, mitochondrial

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000022.10 Reference GRCh37.p10 Primary Assembly

Range

41865129..41924993

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000154.1 Alternate HuRef

Range

24830931..24890807

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018933.1 Alternate CHM1_1.0

Range

25781003..25840864

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01055639.1	None
genomic	ABBA01055640.1	None
genomic	ABBA01055641.1	None
genomic	ABBA01055642.1	None
genomic	AF093096.1	AAD19351.2
genomic	AL008582.11 (70652..98758)	None
genomic	AL023553.5 (101..31858)	None
genomic	AMYH01012803.1 (17381..77242)	None
genomic	CH471095.1	EAW60435.1
		EAW60436.1
genomic	U87926.1	AAC39921.1
genomic	U87927.1	AAC39921.1
genomic	U87928.1	AAC39921.1
genomic	U87929.1	AAC39921.1
genomic	U87930.1	AAC39921.1
genomic	U87931.1	AAC39921.1
genomic	U87932.1	AAC39921.1
genomic	U87933.1	AAC39921.1
genomic	U87934.1	AAC39921.1
genomic	U87935.1	AAC39921.1
genomic	U87936.1	AAC39921.1
genomic	U87937.1	AAC39921.1
genomic	U87938.1	AAC39921.1
genomic	U87939.1	AAC39921.1
mRNA	AA724140.1	None
mRNA	AK293562.1	BAG57034.1
mRNA	AK296260.1	BAG58973.1
mRNA	AK297213.1	BAG59696.1
mRNA	AK301321.1	BAG62870.1
mRNA	AK302691.1	BAG63920.1
mRNA	AK314845.1	BAG37362.1
mRNA	BC014092.2	AAH14092.1
mRNA	BC026196.2	AAH26196.1
mRNA	CR456365.1	CAG30251.1
mRNA	CR536568.1	CAG38805.1
mRNA	U80040.1	AAB38416.1
other-genetic	CU012932.1	CAK54363.1
other-genetic	CU013220.1	CAK54662.1
other-genetic	DQ893674.2	ABM84600.1
other-genetic	DQ895836.2	ABM86762.1