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Protein

Cytoplasmic aconitate hydratase

Gene

ACO1

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

Functioni

Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding.3 Publications
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.By similarity

Catalytic activityi

Citrate = isocitrate.

Cofactori

[4Fe-4S] cluster1 PublicationNote: Binds 1 [4Fe-4S] cluster per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei86SubstrateBy similarity1
Metal bindingi437Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi503Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi506Iron-sulfur (4Fe-4S)By similarity1
Binding sitei536SubstrateBy similarity1
Binding sitei541SubstrateBy similarity1
Binding sitei699SubstrateBy similarity1

GO - Molecular functioni

  • 3 iron, 4 sulfur cluster binding Source: CAFA
  • 4 iron, 4 sulfur cluster binding Source: UniProtKB
  • aconitate hydratase activity Source: UniProtKB
  • iron-responsive element binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionLyase, RNA-binding
Biological processTricarboxylic acid cycle
Ligand4Fe-4S, Iron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS04597-MONOMER
BRENDAi4.2.1.3 2681
ReactomeiR-HSA-917937 Iron uptake and transport
SIGNORiP21399

Protein family/group databases

MoonDBiP21399 Curated
MoonProtiP21399

Names & Taxonomyi

Protein namesi
Recommended name:
Cytoplasmic aconitate hydratase (EC:4.2.1.3)
Short name:
Aconitase
Alternative name(s):
Citrate hydro-lyase
Ferritin repressor protein
Iron regulatory protein 1
Short name:
IRP1
Iron-responsive element-binding protein 1
Short name:
IRE-BP 1
Gene namesi
Name:ACO1
Synonyms:IREB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000122729.18
HGNCiHGNC:117 ACO1
MIMi100880 gene
neXtProtiNX_P21399

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi300C → S: No effect on aconitase activity or on RNA binding. 1 Publication1
Mutagenesisi437C → S: Loss of aconitase activity. Leads to constitutive RNA binding, irrespective of iron levels. 1 Publication1
Mutagenesisi503C → S: Loss of aconitase activity. Leads to constitutive RNA binding, irrespective of iron levels. 1 Publication1
Mutagenesisi506C → S: Loss of aconitase activity. Leads of iron levels. 1 Publication1
Mutagenesisi536R → Q: Strongly reduced RNA binding. 1 Publication1
Mutagenesisi541R → Q: Strongly reduced RNA binding. 1 Publication1
Mutagenesisi699R → K: No effect on RNA binding. 1 Publication1
Mutagenesisi778S → A: No effect on iron-regulated RNA binding. Loss of aconitase activity. 1 Publication1
Mutagenesisi780R → Q: Nearly abolishes RNA binding. 1 Publication1

Organism-specific databases

DisGeNETi48
OpenTargetsiENSG00000122729
PharmGKBiPA24442

Chemistry databases

DrugBankiDB06757 Manganese

Polymorphism and mutation databases

BioMutaiACO1
DMDMi3123225

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766801 – 889Cytoplasmic aconitate hydrataseAdd BLAST889

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei628PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP21399
PaxDbiP21399
PeptideAtlasiP21399
PRIDEiP21399
ProteomicsDBi53867

2D gel databases

REPRODUCTION-2DPAGEiIPI00008485
UCD-2DPAGEiP21399

PTM databases

iPTMnetiP21399
PhosphoSitePlusiP21399
SwissPalmiP21399

Expressioni

Gene expression databases

BgeeiENSG00000122729 Expressed in 220 organ(s), highest expression level in adipose tissue
CleanExiHS_ACO1
ExpressionAtlasiP21399 baseline and differential
GenevisibleiP21399 HS

Organism-specific databases

HPAiHPA019371
HPA024157

Interactioni

Subunit structurei

Interacts (when associated with the 4Fe-4S) with FBXL5. Interacts with frataxin(81-210).4 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi106564, 19 interactors
IntActiP21399, 9 interactors
STRINGi9606.ENSP00000309477

Structurei

Secondary structure

1889
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP21399
SMRiP21399
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21399

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni205 – 207Substrate bindingBy similarity3
Regioni779 – 780Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the aconitase/IPM isomerase family.Curated

Phylogenomic databases

eggNOGiKOG0452 Eukaryota
COG1048 LUCA
GeneTreeiENSGT00920000149090
HOGENOMiHOG000025704
HOVERGENiHBG052147
InParanoidiP21399
KOiK01681
OMAiMRIIPPG
OrthoDBiEOG091G01IX
PhylomeDBiP21399
TreeFamiTF313476

Family and domain databases

Gene3Di3.20.19.10, 1 hit
3.30.499.10, 1 hit
InterProiView protein in InterPro
IPR015931 Acnase/IPM_dHydase_lsu_aba_1/3
IPR001030 Acoase/IPM_deHydtase_lsu_aba
IPR015928 Aconitase/3IPM_dehydase_swvl
IPR006249 Aconitase/IRP2
IPR018136 Aconitase_4Fe-4S_BS
IPR036008 Aconitase_4Fe-4S_dom
IPR000573 AconitaseA/IPMdHydase_ssu_swvl
IPR029784 IRE-BP1
PANTHERiPTHR11670 PTHR11670, 1 hit
PTHR11670:SF32 PTHR11670:SF32, 1 hit
PfamiView protein in Pfam
PF00330 Aconitase, 1 hit
PF00694 Aconitase_C, 1 hit
PRINTSiPR00415 ACONITASE
SUPFAMiSSF53732 SSF53732, 1 hit
TIGRFAMsiTIGR01341 aconitase_1, 1 hit
PROSITEiView protein in PROSITE
PS00450 ACONITASE_1, 1 hit
PS01244 ACONITASE_2, 1 hit

Sequencei

Sequence statusi: Complete.

P21399-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSNPFAHLAE PLDPVQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAIRNC
60 70 80 90 100
DEFLVKKQDI ENILHWNVTQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM
110 120 130 140 150
RDAVKKLGGD PEKINPVCPA DLVIDHSIQV DFNRRADSLQ KNQDLEFERN
160 170 180 190 200
RERFEFLKWG SQAFHNMRII PPGSGIIHQV NLEYLARVVF DQDGYYYPDS
210 220 230 240 250
LVGTDSHTTM IDGLGILGWG VGGIEAEAVM LGQPISMVLP QVIGYRLMGK
260 270 280 290 300
PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC
310 320 330 340 350
PEYGATAAFF PVDEVSITYL VQTGRDEEKL KYIKKYLQAV GMFRDFNDPS
360 370 380 390 400
QDPDFTQVVE LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK
410 420 430 440 450
GFQVAPEHHN DHKTFIYDNT EFTLAHGSVV IAAITSCTNT SNPSVMLGAG
460 470 480 490 500
LLAKKAVDAG LNVMPYIKTS LSPGSGVVTY YLQESGVMPY LSQLGFDVVG
510 520 530 540 550
YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG RVHPNTRANY
560 570 580 590 600
LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE
610 620 630 640 650
RQYVIPGMFK EVYQKIETVN ESWNALATPS DKLFFWNSKS TYIKSPPFFE
660 670 680 690 700
NLTLDLQPPK SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG
710 720 730 740 750
LTPREFNSYG SRRGNDAVMA RGTFANIRLL NRFLNKQAPQ TIHLPSGEIL
760 770 780 790 800
DVFDAAERYQ QAGLPLIVLA GKEYGAGSSR DWAAKGPFLL GIKAVLAESY
810 820 830 840 850
ERIHRSNLVG MGVIPLEYLP GENADALGLT GQERYTIIIP ENLKPQMKVQ
860 870 880
VKLDTGKTFQ AVMRFDTDVE LTYFLNGGIL NYMIRKMAK
Length:889
Mass (Da):98,399
Last modified:July 15, 1998 - v3
Checksum:iE1A05AF701D46DCB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069413318T → M1 PublicationCorresponds to variant dbSNP:rs150373174Ensembl.1
Natural variantiVAR_048180395A → D. Corresponds to variant dbSNP:rs3814519Ensembl.1
Natural variantiVAR_048181486G → R. Corresponds to variant dbSNP:rs34630459Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11559 mRNA Translation: CAA77651.1
DQ496106 Genomic DNA Translation: ABF47095.1
AL161783 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58549.1
CH471071 Genomic DNA Translation: EAW58550.1
CH471071 Genomic DNA Translation: EAW58552.1
BC018103 mRNA Translation: AAH18103.1
M58510 mRNA Translation: AAA69900.1
CCDSiCCDS6525.1
PIRiS26403
RefSeqiNP_001265281.1, NM_001278352.1
NP_002188.1, NM_002197.2
XP_005251533.1, XM_005251476.1
XP_011516190.1, XM_011517888.1
UniGeneiHs.567229

Genome annotation databases

EnsembliENST00000309951; ENSP00000309477; ENSG00000122729
ENST00000379923; ENSP00000369255; ENSG00000122729
ENST00000541043; ENSP00000438733; ENSG00000122729
GeneIDi48
KEGGihsa:48

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Aconitase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11559 mRNA Translation: CAA77651.1
DQ496106 Genomic DNA Translation: ABF47095.1
AL161783 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58549.1
CH471071 Genomic DNA Translation: EAW58550.1
CH471071 Genomic DNA Translation: EAW58552.1
BC018103 mRNA Translation: AAH18103.1
M58510 mRNA Translation: AAA69900.1
CCDSiCCDS6525.1
PIRiS26403
RefSeqiNP_001265281.1, NM_001278352.1
NP_002188.1, NM_002197.2
XP_005251533.1, XM_005251476.1
XP_011516190.1, XM_011517888.1
UniGeneiHs.567229

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2B3XX-ray2.54A2-889[»]
2B3YX-ray1.85A/B2-889[»]
ProteinModelPortaliP21399
SMRiP21399
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106564, 19 interactors
IntActiP21399, 9 interactors
STRINGi9606.ENSP00000309477

Chemistry databases

DrugBankiDB06757 Manganese

Protein family/group databases

MoonDBiP21399 Curated
MoonProtiP21399

PTM databases

iPTMnetiP21399
PhosphoSitePlusiP21399
SwissPalmiP21399

Polymorphism and mutation databases

BioMutaiACO1
DMDMi3123225

2D gel databases

REPRODUCTION-2DPAGEiIPI00008485
UCD-2DPAGEiP21399

Proteomic databases

EPDiP21399
PaxDbiP21399
PeptideAtlasiP21399
PRIDEiP21399
ProteomicsDBi53867

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309951; ENSP00000309477; ENSG00000122729
ENST00000379923; ENSP00000369255; ENSG00000122729
ENST00000541043; ENSP00000438733; ENSG00000122729
GeneIDi48
KEGGihsa:48

Organism-specific databases

CTDi48
DisGeNETi48
EuPathDBiHostDB:ENSG00000122729.18
GeneCardsiACO1
HGNCiHGNC:117 ACO1
HPAiHPA019371
HPA024157
MIMi100880 gene
neXtProtiNX_P21399
OpenTargetsiENSG00000122729
PharmGKBiPA24442
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0452 Eukaryota
COG1048 LUCA
GeneTreeiENSGT00920000149090
HOGENOMiHOG000025704
HOVERGENiHBG052147
InParanoidiP21399
KOiK01681
OMAiMRIIPPG
OrthoDBiEOG091G01IX
PhylomeDBiP21399
TreeFamiTF313476

Enzyme and pathway databases

BioCyciMetaCyc:HS04597-MONOMER
BRENDAi4.2.1.3 2681
ReactomeiR-HSA-917937 Iron uptake and transport
SIGNORiP21399

Miscellaneous databases

ChiTaRSiACO1 human
EvolutionaryTraceiP21399
GenomeRNAii48
PROiPR:P21399
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122729 Expressed in 220 organ(s), highest expression level in adipose tissue
CleanExiHS_ACO1
ExpressionAtlasiP21399 baseline and differential
GenevisibleiP21399 HS

Family and domain databases

Gene3Di3.20.19.10, 1 hit
3.30.499.10, 1 hit
InterProiView protein in InterPro
IPR015931 Acnase/IPM_dHydase_lsu_aba_1/3
IPR001030 Acoase/IPM_deHydtase_lsu_aba
IPR015928 Aconitase/3IPM_dehydase_swvl
IPR006249 Aconitase/IRP2
IPR018136 Aconitase_4Fe-4S_BS
IPR036008 Aconitase_4Fe-4S_dom
IPR000573 AconitaseA/IPMdHydase_ssu_swvl
IPR029784 IRE-BP1
PANTHERiPTHR11670 PTHR11670, 1 hit
PTHR11670:SF32 PTHR11670:SF32, 1 hit
PfamiView protein in Pfam
PF00330 Aconitase, 1 hit
PF00694 Aconitase_C, 1 hit
PRINTSiPR00415 ACONITASE
SUPFAMiSSF53732 SSF53732, 1 hit
TIGRFAMsiTIGR01341 aconitase_1, 1 hit
PROSITEiView protein in PROSITE
PS00450 ACONITASE_1, 1 hit
PS01244 ACONITASE_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACOC_HUMAN
AccessioniPrimary (citable) accession number: P21399
Secondary accession number(s): D3DRK7, Q14652, Q5VZA7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: July 15, 1998
Last modified: September 12, 2018
This is version 191 of the entry and version 3 of the sequence. See 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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