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Protein

Cytoplasmic aconitate hydratase

Gene

ACO1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.2 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

  • 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

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Tricarboxylic acid cycle

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciMetaCyc:HS04597-MONOMER.
ZFISH:HS04597-MONOMER.
BRENDAi4.2.1.3. 2681.
SIGNORiP21399.

Protein family/group databases

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

HGNCiHGNC:117. ACO1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HGNC
  • endoplasmic reticulum Source: MGI
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: MGI
  • mitochondrion Source: HPA
Complete GO annotation...

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.

2D gel databases

REPRODUCTION-2DPAGEIPI00008485.
UCD-2DPAGEP21399.

PTM databases

iPTMnetiP21399.
PhosphoSitePlusiP21399.
SwissPalmiP21399.

Expressioni

Gene expression databases

BgeeiENSG00000122729.
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

WithEntry#Exp.IntActNotes
NEBP209292EBI-2847111,EBI-1049657
SGCGQ133262EBI-2847111,EBI-5357343

Protein-protein interaction databases

BioGridi106564. 17 interactors.
IntActiP21399. 9 interactors.
STRINGi9606.ENSP00000309477.

Structurei

Secondary structure

1889
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 8Combined sources3
Beta strandi9 – 12Combined sources4
Beta strandi20 – 22Combined sources3
Helixi24 – 27Combined sources4
Helixi32 – 34Combined sources3
Helixi37 – 48Combined sources12
Beta strandi52 – 55Combined sources4
Helixi57 – 64Combined sources8
Helixi66 – 69Combined sources4
Turni70 – 73Combined sources4
Beta strandi75 – 78Combined sources4
Beta strandi81 – 86Combined sources6
Helixi87 – 106Combined sources20
Helixi111 – 113Combined sources3
Beta strandi120 – 123Combined sources4
Helixi138 – 163Combined sources26
Beta strandi167 – 170Combined sources4
Helixi177 – 183Combined sources7
Beta strandi188 – 192Combined sources5
Beta strandi195 – 198Combined sources4
Beta strandi200 – 205Combined sources6
Helixi206 – 214Combined sources9
Beta strandi217 – 220Combined sources4
Helixi223 – 230Combined sources8
Beta strandi235 – 238Combined sources4
Beta strandi242 – 249Combined sources8
Helixi257 – 271Combined sources15
Beta strandi277 – 282Combined sources6
Helixi283 – 285Combined sources3
Helixi290 – 298Combined sources9
Helixi300 – 303Combined sources4
Beta strandi306 – 309Combined sources4
Helixi314 – 322Combined sources9
Helixi327 – 340Combined sources14
Helixi349 – 351Combined sources3
Beta strandi356 – 362Combined sources7
Helixi363 – 365Combined sources3
Beta strandi368 – 371Combined sources4
Beta strandi379 – 381Combined sources3
Helixi382 – 384Combined sources3
Helixi385 – 394Combined sources10
Helixi406 – 408Combined sources3
Beta strandi412 – 417Combined sources6
Beta strandi420 – 425Combined sources6
Beta strandi428 – 434Combined sources7
Helixi437 – 440Combined sources4
Helixi443 – 458Combined sources16
Beta strandi467 – 471Combined sources5
Helixi476 – 484Combined sources9
Helixi488 – 493Combined sources6
Beta strandi501 – 503Combined sources3
Helixi504 – 507Combined sources4
Helixi515 – 524Combined sources10
Beta strandi529 – 535Combined sources7
Turni539 – 541Combined sources3
Beta strandi547 – 551Combined sources5
Helixi554 – 563Combined sources10
Beta strandi564 – 566Combined sources3
Turni570 – 572Combined sources3
Beta strandi575 – 578Combined sources4
Turni579 – 581Combined sources3
Beta strandi582 – 584Combined sources3
Helixi586 – 589Combined sources4
Helixi593 – 603Combined sources11
Helixi606 – 613Combined sources8
Turni614 – 618Combined sources5
Helixi621 – 625Combined sources5
Helixi647 – 649Combined sources3
Beta strandi662 – 671Combined sources10
Helixi677 – 680Combined sources4
Beta strandi688 – 690Combined sources3
Helixi691 – 698Combined sources8
Helixi703 – 705Combined sources3
Helixi710 – 712Combined sources3
Helixi716 – 721Combined sources6
Turni722 – 724Combined sources3
Turni732 – 734Combined sources3
Beta strandi735 – 737Combined sources3
Beta strandi739 – 742Combined sources4
Turni744 – 746Combined sources3
Beta strandi749 – 751Combined sources3
Helixi752 – 761Combined sources10
Beta strandi766 – 769Combined sources4
Beta strandi772 – 774Combined sources3
Helixi782 – 789Combined sources8
Beta strandi792 – 798Combined sources7
Helixi802 – 810Combined sources9
Beta strandi814 – 818Combined sources5
Helixi824 – 827Combined sources4
Beta strandi835 – 837Combined sources3
Beta strandi848 – 853Combined sources6
Beta strandi858 – 863Combined sources6
Helixi868 – 876Combined sources9
Helixi879 – 888Combined sources10

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...

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.
GeneTreeiENSGT00860000133751.
HOGENOMiHOG000025704.
HOVERGENiHBG052147.
InParanoidiP21399.
KOiK01681.
OMAiENLAKWG.
OrthoDBiEOG091G01IX.
PhylomeDBiP21399.
TreeFamiTF313476.

Family and domain databases

Gene3Di3.20.19.10. 1 hit.
3.30.499.10. 3 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.
IPR006249. Aconitase/IRP2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
IPR029784. IRE-BP1.
[Graphical view]
PANTHERiPTHR11670. PTHR11670. 4 hits.
PTHR11670:SF32. PTHR11670:SF32. 4 hits.
PfamiPF00330. Aconitase. 1 hit.
PF00694. Aconitase_C. 1 hit.
[Graphical view]
PRINTSiPR00415. ACONITASE.
SUPFAMiSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 1 hit.
TIGRFAMsiTIGR01341. aconitase_1. 1 hit.
PROSITEiPS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.
[Graphical view]

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 → M.1 PublicationCorresponds to variant rs150373174dbSNPEnsembl.1
Natural variantiVAR_048180395A → D.Corresponds to variant rs3814519dbSNPEnsembl.1
Natural variantiVAR_048181486G → R.Corresponds to variant rs34630459dbSNPEnsembl.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. Translation: CAH72598.1.
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

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. Translation: CAH72598.1.
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. 17 interactors.
IntActiP21399. 9 interactors.
STRINGi9606.ENSP00000309477.

Chemistry databases

DrugBankiDB06757. Manganese.

Protein family/group databases

MoonProtiP21399.

PTM databases

iPTMnetiP21399.
PhosphoSitePlusiP21399.
SwissPalmiP21399.

Polymorphism and mutation databases

BioMutaiACO1.
DMDMi3123225.

2D gel databases

REPRODUCTION-2DPAGEIPI00008485.
UCD-2DPAGEP21399.

Proteomic databases

EPDiP21399.
PaxDbiP21399.
PeptideAtlasiP21399.
PRIDEiP21399.

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.
GeneCardsiACO1.
HGNCiHGNC:117. ACO1.
HPAiHPA019371.
HPA024157.
MIMi100880. gene.
neXtProtiNX_P21399.
OpenTargetsiENSG00000122729.
PharmGKBiPA24442.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0452. Eukaryota.
COG1048. LUCA.
GeneTreeiENSGT00860000133751.
HOGENOMiHOG000025704.
HOVERGENiHBG052147.
InParanoidiP21399.
KOiK01681.
OMAiENLAKWG.
OrthoDBiEOG091G01IX.
PhylomeDBiP21399.
TreeFamiTF313476.

Enzyme and pathway databases

BioCyciMetaCyc:HS04597-MONOMER.
ZFISH:HS04597-MONOMER.
BRENDAi4.2.1.3. 2681.
SIGNORiP21399.

Miscellaneous databases

ChiTaRSiACO1. human.
EvolutionaryTraceiP21399.
GenomeRNAii48.
PROiP21399.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122729.
CleanExiHS_ACO1.
ExpressionAtlasiP21399. baseline and differential.
GenevisibleiP21399. HS.

Family and domain databases

Gene3Di3.20.19.10. 1 hit.
3.30.499.10. 3 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.
IPR006249. Aconitase/IRP2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
IPR029784. IRE-BP1.
[Graphical view]
PANTHERiPTHR11670. PTHR11670. 4 hits.
PTHR11670:SF32. PTHR11670:SF32. 4 hits.
PfamiPF00330. Aconitase. 1 hit.
PF00694. Aconitase_C. 1 hit.
[Graphical view]
PRINTSiPR00415. ACONITASE.
SUPFAMiSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 1 hit.
TIGRFAMsiTIGR01341. aconitase_1. 1 hit.
PROSITEiPS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACOC_HUMAN
AccessioniPrimary (citable) accession number: P21399
Secondary accession number(s): D3DRK7, Q14652, Q5VZA7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: July 15, 1998
Last modified: November 30, 2016
This is version 177 of the entry and version 3 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

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

Documents

  1. Human chromosome 9
    Human chromosome 9: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.