ACO2

Protein identityUniProt · HPA

UniProt accession

Q99798

Gene

ACO2

Ensembl

ENSG00000100412

Chromosome

22

Canonical length

780 aa

Protein class

Citric acid cycle related proteins, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

780 residues, UniProt reviewed canonical sequence.

>Q99798|ACO2
     1  MAPYSLLVTR LQKALGVRQY HVASVLCQRA KVAMSHFEPN EYIHYDLLEK NINIVRKRLN
    61  RPLTLSEKIV YGHLDDPASQ EIERGKSYLR LRPDRVAMQD ATAQMAMLQF ISSGLSKVAV
   121  PSTIHCDHLI EAQVGGEKDL RRAKDINQEV YNFLATAGAK YGVGFWKPGS GIIHQIILEN
   181  YAYPGVLLIG TDSHTPNGGG LGGICIGVGG ADAVDVMAGI PWELKCPKVI GVKLTGSLSG
   241  WSSPKDVILK VAGILTVKGG TGAIVEYHGP GVDSISCTGM ATICNMGAEI GATTSVFPYN
   301  HRMKKYLSKT GREDIANLAD EFKDHLVPDP GCHYDQLIEI NLSELKPHIN GPFTPDLAHP
   361  VAEVGKVAEK EGWPLDIRVG LIGSCTNSSY EDMGRSAAVA KQALAHGLKC KSQFTITPGS
   421  EQIRATIERD GYAQILRDLG GIVLANACGP CIGQWDRKDI KKGEKNTIVT SYNRNFTGRN
   481  DANPETHAFV TSPEIVTALA IAGTLKFNPE TDYLTGTDGK KFRLEAPDAD ELPKGEFDPG
   541  QDTYQHPPKD SSGQHVDVSP TSQRLQLLEP FDKWDGKDLE DLQILIKVKG KCTTDHISAA
   601  GPWLKFRGHL DNISNNLLIG AINIENGKAN SVRNAVTQEF GPVPDTARYY KKHGIRWVVI
   661  GDENYGEGSS REHAALEPRH LGGRAIITKS FARIHETNLK KQGLLPLTFA DPADYNKIHP
   721  VDKLTIQGLK DFTPGKPLKC IIKHPNGTQE TILLNHTFNE TQIEWFRAGS ALNRMKELQQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACO2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.2

Highest tissue expression

650 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACO2.

Disease | AllUniProt

Conditions ACO2 is implicated in, by any mechanism.

• Infantile cerebellar-retinal degeneration (ICRD) MIM:614559
• Optic atrophy 9 (OPA9) MIM:616289

Disease | GeneticClinVar

83 pathogenic / likely-pathogenic of 907 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Infantile cerebellar-retinal degeneration
• Optic atrophy 9
• Optic atrophy
• ACO2-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.42

gnomAD pLI

0.21

gnomAD missense Z

2.92

DepMap mean gene effect

-0.76

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• citrate metabolic process
• generation of precursor metabolites and energy
• tricarboxylic acid cycle

Molecular functions

• 4 iron, 4 sulfur cluster binding
• aconitate hydratase activity
• iron ion binding

Cellular components

• cytosol
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
• Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
• Aconitase/3-isopropylmalate dehydratase, swivel
• Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
• Aconitase family, 4Fe-4S cluster binding site
• Aconitase, iron-sulfur domain
• Aconitase family (aconitate hydratase)
• Aconitase C-terminal domain
• Aconitase, mitochondrial-like
• Aconitase, domain 2
• Aconitase/IPM Isomerase

KeywordsUniProt

• 4Fe-4S
• Acetylation
• Iron
• Iron-sulfur
• Lyase
• Metal-binding
• Mitochondrion
• Neurodegeneration
• Phosphoprotein
• Transit peptide
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of ACO2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FXN