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Protein

Aconitate hydratase, mitochondrial

Gene

ACO2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.By similarity

Catalytic activityi

Citrate = isocitrate.

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster per subunit. Binding of a [3Fe-4S] cluster leads to an inactive enzyme.By similarity

Pathwayi: tricarboxylic acid cycle

This protein is involved in step 2 of the subpathway that synthesizes isocitrate from oxaloacetate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Citrate synthase, mitochondrial (CS)
  2. Aconitate hydratase, mitochondrial (ACO2)
This subpathway is part of the pathway tricarboxylic acid cycle, which is itself part of Carbohydrate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes isocitrate from oxaloacetate, the pathway tricarboxylic acid cycle and in Carbohydrate metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei99SubstrateBy similarity1
Metal bindingi385Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi448Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi451Iron-sulfur (4Fe-4S)By similarity1
Binding sitei474SubstrateBy similarity1
Binding sitei479SubstrateBy similarity1
Binding sitei607SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • citrate metabolic process Source: MGI
  • generation of precursor metabolites and energy Source: ProtInc
  • isocitrate metabolic process Source: Ensembl
  • tricarboxylic acid cycle Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Tricarboxylic acid cycle

Keywords - Ligandi

4Fe-4S, Iron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02077-MONOMER.
ZFISH:HS02077-MONOMER.
BRENDAi4.2.1.3. 2681.
ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-71403. Citric acid cycle (TCA cycle).
UniPathwayiUPA00223; UER00718.

Names & Taxonomyi

Protein namesi
Recommended name:
Aconitate hydratase, mitochondrial (EC:4.2.1.3)
Short name:
Aconitase
Alternative name(s):
Citrate hydro-lyase
Gene namesi
Name:ACO2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:118. ACO2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
  • myelin sheath Source: Ensembl
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Infantile cerebellar-retinal degeneration (ICRD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration.
See also OMIM:614559
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067543112S → R in ICRD; functional expression studies in yeast show that the mutant has decreased function under growth conditions requiring the TCA cycle and the glyoxylate shunt. 1 PublicationCorresponds to variant rs786200924dbSNPEnsembl.1
Natural variantiVAR_073436259G → D in ICRD. 1 PublicationCorresponds to variant rs786204828dbSNPEnsembl.1
Natural variantiVAR_073438736K → N in ICRD. 1 PublicationCorresponds to variant rs786204829dbSNPEnsembl.1
Optic atrophy 9 (OPA9)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.
See also OMIM:616289
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07343574L → V in OPA9. 1 PublicationCorresponds to variant rs141772938dbSNPEnsembl.1
Natural variantiVAR_073437661G → R in OPA9. 1 PublicationCorresponds to variant rs752034900dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi50.
MalaCardsiACO2.
MIMi614559. phenotype.
616289. phenotype.
OpenTargetsiENSG00000100412.
Orphaneti313850. Infantile cerebellar-retinal degeneration.
PharmGKBiPA24443.

Polymorphism and mutation databases

BioMutaiACO2.
DMDMi6686275.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 27MitochondrionBy similarityAdd BLAST27
ChainiPRO_000000054128 – 780Aconitate hydratase, mitochondrialAdd BLAST753

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28Pyrrolidone carboxylic acidBy similarity1
Modified residuei31N6-succinyllysineBy similarity1
Modified residuei50N6-acetyllysine; alternateBy similarity1
Modified residuei50N6-succinyllysine; alternateBy similarity1
Modified residuei138N6-acetyllysine; alternateBy similarity1
Modified residuei138N6-succinyllysine; alternateBy similarity1
Modified residuei144N6-acetyllysine; alternateBy similarity1
Modified residuei144N6-succinyllysine; alternateBy similarity1
Modified residuei233N6-acetyllysine; alternateBy similarity1
Modified residuei233N6-succinyllysine; alternateBy similarity1
Modified residuei411N6-succinyllysineBy similarity1
Modified residuei549N6-succinyllysineBy similarity1
Modified residuei559PhosphoserineCombined sources1
Modified residuei573N6-acetyllysine; alternateCombined sources1
Modified residuei573N6-succinyllysine; alternateBy similarity1
Modified residuei577N6-succinyllysineBy similarity1
Modified residuei591N6-succinyllysineBy similarity1
Modified residuei605N6-acetyllysine; alternateCombined sources1
Modified residuei605N6-succinyllysine; alternateBy similarity1
Modified residuei628N6-succinyllysineBy similarity1
Modified residuei670PhosphoserineBy similarity1
Modified residuei689N6-succinyllysineBy similarity1
Modified residuei723N6-acetyllysine; alternateBy similarity1
Modified residuei723N6-succinyllysine; alternateBy similarity1
Modified residuei730N6-acetyllysine; alternateBy similarity1
Modified residuei730N6-succinyllysine; alternateBy similarity1
Modified residuei736N6-acetyllysineBy similarity1
Modified residuei739N6-acetyllysineBy similarity1
Modified residuei743N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein, Pyrrolidone carboxylic acid

Proteomic databases

EPDiQ99798.
MaxQBiQ99798.
PaxDbiQ99798.
PeptideAtlasiQ99798.
PRIDEiQ99798.

2D gel databases

DOSAC-COBS-2DPAGEQ99798.
REPRODUCTION-2DPAGEIPI00017855.
Q99798.
SWISS-2DPAGEQ99798.
UCD-2DPAGEQ99798.

PTM databases

iPTMnetiQ99798.
PhosphoSitePlusiQ99798.
SwissPalmiQ99798.

Expressioni

Gene expression databases

BgeeiENSG00000100412.
CleanExiHS_ACO2.
ExpressionAtlasiQ99798. baseline and differential.
GenevisibleiQ99798. HS.

Organism-specific databases

HPAiHPA001097.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

BioGridi106566. 29 interactors.
IntActiQ99798. 3 interactors.
MINTiMINT-2856402.
STRINGi9606.ENSP00000216254.

Structurei

3D structure databases

ProteinModelPortaliQ99798.
SMRiQ99798.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni192 – 194Substrate bindingBy similarity3
Regioni670 – 671Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the aconitase/IPM isomerase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0453. Eukaryota.
COG1048. LUCA.
GeneTreeiENSGT00860000133751.
HOGENOMiHOG000224293.
HOVERGENiHBG000248.
InParanoidiQ99798.
KOiK01681.
PhylomeDBiQ99798.
TreeFamiTF300627.

Family and domain databases

Gene3Di3.20.19.10. 1 hit.
3.30.499.10. 2 hits.
3.40.1060.10. 1 hit.
InterProiIPR015931. Acnase/IPM_dHydase_lsu_aba_1/3.
IPR015937. Acoase/IPM_deHydtase.
IPR001030. Acoase/IPM_deHydtase_lsu_aba.
IPR015928. Aconitase/3IPM_dehydase_swvl.
IPR015932. Aconitase/IPMdHydase_lsu_aba_2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR006248. Aconitase_mito-like.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
[Graphical view]
PANTHERiPTHR11670. PTHR11670. 1 hit.
PfamiPF00330. Aconitase. 1 hit.
PF00694. Aconitase_C. 1 hit.
[Graphical view]
PRINTSiPR00415. ACONITASE.
SUPFAMiSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 1 hit.
TIGRFAMsiTIGR01340. aconitase_mito. 1 hit.
PROSITEiPS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99798-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPYSLLVTR LQKALGVRQY HVASVLCQRA KVAMSHFEPN EYIHYDLLEK
60 70 80 90 100
NINIVRKRLN RPLTLSEKIV YGHLDDPASQ EIERGKSYLR LRPDRVAMQD
110 120 130 140 150
ATAQMAMLQF ISSGLSKVAV PSTIHCDHLI EAQVGGEKDL RRAKDINQEV
160 170 180 190 200
YNFLATAGAK YGVGFWKPGS GIIHQIILEN YAYPGVLLIG TDSHTPNGGG
210 220 230 240 250
LGGICIGVGG ADAVDVMAGI PWELKCPKVI GVKLTGSLSG WSSPKDVILK
260 270 280 290 300
VAGILTVKGG TGAIVEYHGP GVDSISCTGM ATICNMGAEI GATTSVFPYN
310 320 330 340 350
HRMKKYLSKT GREDIANLAD EFKDHLVPDP GCHYDQLIEI NLSELKPHIN
360 370 380 390 400
GPFTPDLAHP VAEVGKVAEK EGWPLDIRVG LIGSCTNSSY EDMGRSAAVA
410 420 430 440 450
KQALAHGLKC KSQFTITPGS EQIRATIERD GYAQILRDLG GIVLANACGP
460 470 480 490 500
CIGQWDRKDI KKGEKNTIVT SYNRNFTGRN DANPETHAFV TSPEIVTALA
510 520 530 540 550
IAGTLKFNPE TDYLTGTDGK KFRLEAPDAD ELPKGEFDPG QDTYQHPPKD
560 570 580 590 600
SSGQHVDVSP TSQRLQLLEP FDKWDGKDLE DLQILIKVKG KCTTDHISAA
610 620 630 640 650
GPWLKFRGHL DNISNNLLIG AINIENGKAN SVRNAVTQEF GPVPDTARYY
660 670 680 690 700
KKHGIRWVVI GDENYGEGSS REHAALEPRH LGGRAIITKS FARIHETNLK
710 720 730 740 750
KQGLLPLTFA DPADYNKIHP VDKLTIQGLK DFTPGKPLKC IIKHPNGTQE
760 770 780
TILLNHTFNE TQIEWFRAGS ALNRMKELQQ
Length:780
Mass (Da):85,425
Last modified:May 30, 2000 - v2
Checksum:i58C9FFBDBDC63D5E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti35S → T in AAB38416 (Ref. 1) Curated1
Sequence conflicti136G → D in AAB38416 (Ref. 1) Curated1
Sequence conflicti159A → D in AAB38416 (Ref. 1) Curated1
Sequence conflicti167K → S in AAB38416 (Ref. 1) Curated1
Sequence conflicti199G → D in CAG38805 (Ref. 4) Curated1
Sequence conflicti207G → R in AAH26196 (PubMed:15489334).Curated1
Sequence conflicti242S → T in AAB38416 (Ref. 1) Curated1
Sequence conflicti270P → H in AAH26196 (PubMed:15489334).Curated1
Sequence conflicti275I → M in AAB38416 (Ref. 1) Curated1
Sequence conflicti444L → P in CAG38805 (Ref. 4) Curated1
Sequence conflicti517T → K in AAB38416 (Ref. 1) Curated1
Sequence conflicti553G → R in AAB38416 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07343574L → V in OPA9. 1 PublicationCorresponds to variant rs141772938dbSNPEnsembl.1
Natural variantiVAR_067543112S → R in ICRD; functional expression studies in yeast show that the mutant has decreased function under growth conditions requiring the TCA cycle and the glyoxylate shunt. 1 PublicationCorresponds to variant rs786200924dbSNPEnsembl.1
Natural variantiVAR_073436259G → D in ICRD. 1 PublicationCorresponds to variant rs786204828dbSNPEnsembl.1
Natural variantiVAR_073437661G → R in OPA9. 1 PublicationCorresponds to variant rs752034900dbSNPEnsembl.1
Natural variantiVAR_036572697T → N in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_073438736K → N in ICRD. 1 PublicationCorresponds to variant rs786204829dbSNPEnsembl.1
Natural variantiVAR_033297768A → S.Corresponds to variant rs1804785dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U80040 mRNA. Translation: AAB38416.1.
U87939
, U87926, U87927, U87928, U87929, U87930, U87931, U87932, U87933, U87934, U87935, U87936, U87937, U87938 Genomic DNA. Translation: AAC39921.1.
CR456365 mRNA. Translation: CAG30251.1.
CR536568 mRNA. Translation: CAG38805.1.
AL023553, AL008582 Genomic DNA. Translation: CAI20278.1.
AL008582, AL023553 Genomic DNA. Translation: CAI17931.1.
BC014092 mRNA. Translation: AAH14092.1.
BC026196 mRNA. Translation: AAH26196.1.
CCDSiCCDS14017.1.
PIRiS17526.
T52543.
RefSeqiNP_001089.1. NM_001098.2.
UniGeneiHs.643610.

Genome annotation databases

EnsembliENST00000216254; ENSP00000216254; ENSG00000100412.
GeneIDi50.
KEGGihsa:50.
UCSCiuc003bac.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Aconitase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U80040 mRNA. Translation: AAB38416.1.
U87939
, U87926, U87927, U87928, U87929, U87930, U87931, U87932, U87933, U87934, U87935, U87936, U87937, U87938 Genomic DNA. Translation: AAC39921.1.
CR456365 mRNA. Translation: CAG30251.1.
CR536568 mRNA. Translation: CAG38805.1.
AL023553, AL008582 Genomic DNA. Translation: CAI20278.1.
AL008582, AL023553 Genomic DNA. Translation: CAI17931.1.
BC014092 mRNA. Translation: AAH14092.1.
BC026196 mRNA. Translation: AAH26196.1.
CCDSiCCDS14017.1.
PIRiS17526.
T52543.
RefSeqiNP_001089.1. NM_001098.2.
UniGeneiHs.643610.

3D structure databases

ProteinModelPortaliQ99798.
SMRiQ99798.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106566. 29 interactors.
IntActiQ99798. 3 interactors.
MINTiMINT-2856402.
STRINGi9606.ENSP00000216254.

PTM databases

iPTMnetiQ99798.
PhosphoSitePlusiQ99798.
SwissPalmiQ99798.

Polymorphism and mutation databases

BioMutaiACO2.
DMDMi6686275.

2D gel databases

DOSAC-COBS-2DPAGEQ99798.
REPRODUCTION-2DPAGEIPI00017855.
Q99798.
SWISS-2DPAGEQ99798.
UCD-2DPAGEQ99798.

Proteomic databases

EPDiQ99798.
MaxQBiQ99798.
PaxDbiQ99798.
PeptideAtlasiQ99798.
PRIDEiQ99798.

Protocols and materials databases

DNASUi50.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216254; ENSP00000216254; ENSG00000100412.
GeneIDi50.
KEGGihsa:50.
UCSCiuc003bac.3. human.

Organism-specific databases

CTDi50.
DisGeNETi50.
GeneCardsiACO2.
HGNCiHGNC:118. ACO2.
HPAiHPA001097.
MalaCardsiACO2.
MIMi100850. gene.
614559. phenotype.
616289. phenotype.
neXtProtiNX_Q99798.
OpenTargetsiENSG00000100412.
Orphaneti313850. Infantile cerebellar-retinal degeneration.
PharmGKBiPA24443.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0453. Eukaryota.
COG1048. LUCA.
GeneTreeiENSGT00860000133751.
HOGENOMiHOG000224293.
HOVERGENiHBG000248.
InParanoidiQ99798.
KOiK01681.
PhylomeDBiQ99798.
TreeFamiTF300627.

Enzyme and pathway databases

UniPathwayiUPA00223; UER00718.
BioCyciMetaCyc:HS02077-MONOMER.
ZFISH:HS02077-MONOMER.
BRENDAi4.2.1.3. 2681.
ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-71403. Citric acid cycle (TCA cycle).

Miscellaneous databases

ChiTaRSiACO2. human.
GenomeRNAii50.
PROiQ99798.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100412.
CleanExiHS_ACO2.
ExpressionAtlasiQ99798. baseline and differential.
GenevisibleiQ99798. HS.

Family and domain databases

Gene3Di3.20.19.10. 1 hit.
3.30.499.10. 2 hits.
3.40.1060.10. 1 hit.
InterProiIPR015931. Acnase/IPM_dHydase_lsu_aba_1/3.
IPR015937. Acoase/IPM_deHydtase.
IPR001030. Acoase/IPM_deHydtase_lsu_aba.
IPR015928. Aconitase/3IPM_dehydase_swvl.
IPR015932. Aconitase/IPMdHydase_lsu_aba_2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR006248. Aconitase_mito-like.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
[Graphical view]
PANTHERiPTHR11670. PTHR11670. 1 hit.
PfamiPF00330. Aconitase. 1 hit.
PF00694. Aconitase_C. 1 hit.
[Graphical view]
PRINTSiPR00415. ACONITASE.
SUPFAMiSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 1 hit.
TIGRFAMsiTIGR01340. aconitase_mito. 1 hit.
PROSITEiPS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACON_HUMAN
AccessioniPrimary (citable) accession number: Q99798
Secondary accession number(s): O75809
, Q5JZ41, Q6FHX0, Q8TAQ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: November 30, 2016
This is version 174 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.