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P21399 (ACOC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytoplasmic aconitate hydratase

Short name=Aconitase
EC=4.2.1.3
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 names
Name:ACO1
Synonyms:IREB1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length889 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Catalyzes the isomerization of citrate to isocitrate via cis-aconitate By similarity. Ref.8 Ref.9

Catalytic activity

Citrate = isocitrate.

Cofactor

Binds 1 4Fe-4S cluster per subunit. Ref.14

Subunit structure

Interacts (when associated with the 4Fe-4S) with FBXL5. Interacts with frataxin(81-210). Ref.10 Ref.11 Ref.12

Subcellular location

Cytoplasm.

Sequence similarities

Belongs to the aconitase/IPM isomerase family.

Ontologies

Keywords
   Biological processTricarboxylic acid cycle
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   Ligand4Fe-4S
Iron
Iron-sulfur
Metal-binding
RNA-binding
   Molecular functionLyase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular iron ion homeostasis

Inferred from electronic annotation. Source: Ensembl

citrate metabolic process

Inferred from direct assay Ref.9. Source: UniProtKB

intestinal absorption

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

regulation of translation

Inferred from electronic annotation. Source: Ensembl

response to iron(II) ion

Inferred from direct assay Ref.9. Source: UniProtKB

tricarboxylic acid cycle

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 16144863. Source: MGI

cytoplasm

Non-traceable author statement Ref.1. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 16527810. Source: HGNC

endoplasmic reticulum

Inferred from direct assay PubMed 16144863. Source: MGI

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

mitochondrion

Inferred from direct assay. Source: HPA

   Molecular_function4 iron, 4 sulfur cluster binding

Inferred from direct assay Ref.14. Source: UniProtKB

RNA binding

Inferred from direct assay Ref.8. Source: UniProtKB

aconitate hydratase activity

Inferred from direct assay Ref.8Ref.9. Source: UniProtKB

iron-responsive element binding

Inferred from direct assay Ref.9. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 889889Cytoplasmic aconitate hydratase
PRO_0000076680

Regions

Region205 – 2073Substrate binding By similarity
Region779 – 7802Substrate binding By similarity

Sites

Metal binding4371Iron-sulfur (4Fe-4S) By similarity
Metal binding5031Iron-sulfur (4Fe-4S) By similarity
Metal binding5061Iron-sulfur (4Fe-4S) By similarity
Binding site861Substrate By similarity
Binding site5361Substrate By similarity
Binding site5411Substrate By similarity
Binding site6991Substrate By similarity

Natural variations

Natural variant3181T → M. Ref.15
VAR_069413
Natural variant3951A → D.
Corresponds to variant rs3814519 [ dbSNP | Ensembl ].
VAR_048180
Natural variant4861G → R.
Corresponds to variant rs34630459 [ dbSNP | Ensembl ].
VAR_048181

Experimental info

Mutagenesis3001C → S: No effect on aconitase activity or on RNA binding. Ref.9
Mutagenesis4371C → S: Loss of aconitase activity. Leads to constitutive RNA binding, irrespective of iron levels. Ref.9
Mutagenesis5031C → S: Loss of aconitase activity. Leads to constitutive RNA binding, irrespective of iron levels. Ref.9
Mutagenesis5061C → S: Loss of aconitase activity. Leads of iron levels. Ref.9
Mutagenesis5361R → Q: Strongly reduced RNA binding. Ref.9
Mutagenesis5411R → Q: Strongly reduced RNA binding. Ref.9
Mutagenesis6991R → K: No effect on RNA binding. Ref.9
Mutagenesis7781S → A: No effect on iron-regulated RNA binding. Loss of aconitase activity. Ref.9
Mutagenesis7801R → Q: Nearly abolishes RNA binding. Ref.9

Secondary structure

............................................................................................................................................................................ 889
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P21399 [UniParc].

Last modified July 15, 1998. Version 3.
Checksum: E1A05AF701D46DCB

FASTA88998,399
        10         20         30         40         50         60 
MSNPFAHLAE PLDPVQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAIRNC DEFLVKKQDI 

        70         80         90        100        110        120 
ENILHWNVTQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGD PEKINPVCPA 

       130        140        150        160        170        180 
DLVIDHSIQV DFNRRADSLQ KNQDLEFERN RERFEFLKWG SQAFHNMRII PPGSGIIHQV 

       190        200        210        220        230        240 
NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGILGWG VGGIEAEAVM LGQPISMVLP 

       250        260        270        280        290        300 
QVIGYRLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC 

       310        320        330        340        350        360 
PEYGATAAFF PVDEVSITYL VQTGRDEEKL KYIKKYLQAV GMFRDFNDPS QDPDFTQVVE 

       370        380        390        400        410        420 
LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPEHHN DHKTFIYDNT 

       430        440        450        460        470        480 
EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LNVMPYIKTS LSPGSGVVTY 

       490        500        510        520        530        540 
YLQESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG 

       550        560        570        580        590        600 
RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE 

       610        620        630        640        650        660 
RQYVIPGMFK EVYQKIETVN ESWNALATPS DKLFFWNSKS TYIKSPPFFE NLTLDLQPPK 

       670        680        690        700        710        720 
SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAVMA 

       730        740        750        760        770        780 
RGTFANIRLL NRFLNKQAPQ TIHLPSGEIL DVFDAAERYQ QAGLPLIVLA GKEYGAGSSR 

       790        800        810        820        830        840 
DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GENADALGLT GQERYTIIIP 

       850        860        870        880 
ENLKPQMKVQ VKLDTGKTFQ AVMRFDTDVE LTYFLNGGIL NYMIRKMAK 

« Hide

References

« Hide 'large scale' references
[1]"Expression of active iron regulatory factor from a full-length human cDNA by in vitro transcription/translation."
Hirling H., Emery-Goodman A., Thompson N., Neupert B., Seiser C., Kuehn L.
Nucleic Acids Res. 20:33-39(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]NHLBI resequencing and genotyping service (RS&G)
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[6]"Cloning of the cDNA encoding an RNA regulatory protein -- the human iron-responsive element-binding protein."
Rouault T.A., Tang C.K., Kaptain S., Burgess W.H., Haile D.J., Samaniego F., McBride O.W., Harford J.B., Klausner R.D.
Proc. Natl. Acad. Sci. U.S.A. 87:7958-7962(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 74-889, RNA-BINDING, PARTIAL PROTEIN SEQUENCE.
[7]"Homology between IRE-BP, a regulatory RNA-binding protein, aconitase, and isopropylmalate isomerase."
Hentze M.W., Argos P.
Nucleic Acids Res. 19:1739-1740(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SIMILARITY TO ACONITASES AND IPM ISOMERASES.
[8]"A regulated RNA binding protein also possesses aconitase activity."
Kaptain S., Downey W.E., Tang C.K., Philpott C., Haile D.J., Orloff D.G., Harford J.B., Rouault T.A., Klausner R.D.
Proc. Natl. Acad. Sci. U.S.A. 88:10109-10113(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN ACONITASE.
[9]"The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation."
Philpott C.C., Klausner R.D., Rouault T.A.
Proc. Natl. Acad. Sci. U.S.A. 91:7321-7325(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-300; CYS-437; CYS-503; CYS-506; ARG-536; ARG-541; ARG-699; SER-778 AND ARG-780.
[10]"Control of iron homeostasis by an iron-regulated ubiquitin ligase."
Vashisht A.A., Zumbrennen K.B., Huang X., Powers D.N., Durazo A., Sun D., Bhaskaran N., Persson A., Uhlen M., Sangfelt O., Spruck C., Leibold E.A., Wohlschlegel J.A.
Science 326:718-721(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH FBXL5.
[11]"An E3 ligase possessing an iron responsive hemerythrin domain is a regulator of iron homeostasis."
Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.-W., Kinch L.N., Li Q., Grishin N.V., Bruick R.K.
Science 326:722-726(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH FBXL5.
[12]"Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin."
Condo I., Malisan F., Guccini I., Serio D., Rufini A., Testi R.
Hum. Mol. Genet. 19:1221-1229(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FRATAXIN(81-210).
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Crystal structure of human iron regulatory protein 1 as cytosolic aconitase."
Dupuy J., Volbeda A., Carpentier P., Darnault C., Moulis J.-M., Fontecilla-Camps J.C.
Structure 14:129-139(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR CLUSTER, COFACTOR.
[15]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-318.
+Additional computationally mapped references.

Web resources

Wikipedia

Aconitase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS26403.
RefSeqNP_001265281.1. NM_001278352.1.
NP_002188.1. NM_002197.2.
XP_005251533.1. XM_005251476.1.
UniGeneHs.567229.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2B3XX-ray2.54A2-889[»]
2B3YX-ray1.85A/B2-889[»]
ProteinModelPortalP21399.
SMRP21399. Positions 2-889.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106564. 13 interactions.
IntActP21399. 8 interactions.
STRING9606.ENSP00000309477.

PTM databases

PhosphoSiteP21399.

Polymorphism databases

DMDM3123225.

2D gel databases

REPRODUCTION-2DPAGEIPI00008485.
UCD-2DPAGEP21399.

Proteomic databases

PaxDbP21399.
PeptideAtlasP21399.
PRIDEP21399.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309951; ENSP00000309477; ENSG00000122729.
ENST00000379923; ENSP00000369255; ENSG00000122729.
GeneID48.
KEGGhsa:48.
UCSCuc003zqw.4. human.

Organism-specific databases

CTD48.
GeneCardsGC09P032374.
HGNCHGNC:117. ACO1.
HPAHPA019371.
HPA024157.
MIM100880. gene.
neXtProtNX_P21399.
PharmGKBPA24442.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1048.
HOGENOMHOG000025704.
HOVERGENHBG052147.
InParanoidP21399.
KOK01681.
OMASVMMAAG.
OrthoDBEOG7CG6Z7.
PhylomeDBP21399.
TreeFamTF313476.

Enzyme and pathway databases

BioCycMetaCyc:HS04597-MONOMER.

Gene expression databases

ArrayExpressP21399.
BgeeP21399.
CleanExHS_ACO1.
GenevestigatorP21399.

Family and domain databases

Gene3D3.20.19.10. 1 hit.
3.30.499.10. 3 hits.
3.40.1060.10. 1 hit.
InterProIPR015931. Acnase/IPM_dHydase_lsu_aba_1/3.
IPR015937. Acoase/IPM_deHydtase.
IPR001030. Acoase/IPM_deHydtase_lsu_aba.
IPR015928. Aconitase/3IPM_dehydase_swvl.
IPR006249. Aconitase/Fe_reg_prot_2.
IPR015934. Aconitase/Fe_reg_prot_2/AcnD.
IPR015932. Aconitase/IPMdHydase_lsu_aba_2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
[Graphical view]
PANTHERPTHR11670. PTHR11670. 1 hit.
PTHR11670:SF1. PTHR11670:SF1. 1 hit.
PfamPF00330. Aconitase. 1 hit.
PF00694. Aconitase_C. 1 hit.
[Graphical view]
PRINTSPR00415. ACONITASE.
SUPFAMSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 1 hit.
TIGRFAMsTIGR01341. aconitase_1. 1 hit.
PROSITEPS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP21399.
GenomeRNAi48.
NextBio187.
PROP21399.
SOURCESearch...

Entry information

Entry nameACOC_HUMAN
AccessionPrimary (citable) accession number: P21399
Secondary accession number(s): D3DRK7, Q14652, Q5VZA7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 150 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM