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Identification
HMDB Protein ID HMDBP00726
Secondary Accession Numbers
  • 6001
Name Cytoplasmic aconitate hydratase
Synonyms
  1. Aconitase
  2. Citrate hydro-lyase
  3. Ferritin repressor protein
  4. IRE-BP 1
  5. IRP1
  6. Iron regulatory protein 1
  7. Iron-responsive element-binding protein 1
Gene Name ACO1
Protein Type Unknown
Biological Properties
General Function Involved in metabolic process
Specific 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. Catalyzes the isomerization of citrate to isocitrate via cis-aconitate (By similarity).
Pathways
  • 2-Oxocarboxylic acid metabolism
  • Citrate cycle (TCA cycle)
  • Glyoxylate and dicarboxylate metabolism
  • Lysine biosynthesis
  • The oncogenic action of 2-hydroxyglutarate
  • The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria
  • The Oncogenic Action of Fumarate
  • The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria
  • The Oncogenic Action of Succinate
  • Warburg Effect
Reactions
Citric acid → Isocitric acid details
Citric acid → cis-Aconitic acid + Water details
Isocitric acid → cis-Aconitic acid + Water details
Homocitric acid → (Z)-But-1-ene-1,2,4-tricarboxylate + Water details
GO Classification
Biological Process
citrate metabolic process
cellular iron ion homeostasis
intestinal absorption
regulation of translation
response to iron(II) ion
tricarboxylic acid cycle
post-embryonic development
Cellular Component
cytosol
endoplasmic reticulum
mitochondrion
Golgi apparatus
Function
binding
metal cluster binding
iron-sulfur cluster binding
4 iron, 4 sulfur cluster binding
Molecular Function
metal ion binding
4 iron, 4 sulfur cluster binding
aconitate hydratase activity
citrate hydro-lyase (cis-aconitate-forming) activity
iron-responsive element binding
isocitrate hydro-lyase (cis-aconitate-forming) activity
mRNA 5'-UTR binding
Process
metabolic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 9
Locus 9p21.1
SNPs ACO1
Gene Sequence
>2670 bp
ATGAGCAACCCATTCGCACACCTTGCTGAGCCATTGGATCCTGTACAACCAGGAAAGAAA
TTCTTCAATTTGAATAAATTGGAGGATTCAAGATATGGGCGCTTACCATTTTCGATCAGA
GTTCTTCTGGAAGCAGCCATTCGGAATTGTGATGAGTTTTTGGTGAAGAAACAGGATATT
GAAAATATTCTACATTGGAATGTCACTCAGCACAAGAACATAGAAGTGCCATTTAAGCCT
GCTCGTGTCATCCTGCAGGACTTTACGGGTGTGCCCGCTGTGGTTGACTTTGCTGCAATG
CGTGATGCTGTGAAAAAGTTAGGAGGAGATCCAGAGAAAATAAACCCTGTCTGCCCTGCT
GATCTTGTAATAGATCATTCCATCCAGGTTGATTTCAACAGAAGGGCAGACAGTTTACAG
AAGAATCAAGACCTGGAATTTGAAAGAAATAGAGAGCGATTTGAATTTTTAAAGTGGGGT
TCCCAGGCTTTTCACAACATGCGGATTATTCCCCCTGGCTCAGGAATCATCCACCAGGTG
AATTTGGAATATTTGGCAAGAGTGGTATTTGATCAGGATGGATATTATTACCCAGACAGC
CTCGTGGGCACAGACTCGCACACTACCATGATTGATGGCTTGGGCATTCTTGGTTGGGGT
GTCGGTGGTATTGAAGCAGAAGCTGTCATGCTGGGTCAGCCAATCAGTATGGTGCTTCCT
CAGGTGATTGGCTACAGGCTGATGGGGAAGCCCCACCCTCTGGTAACATCCACTGACATC
GTGCTCACCATTACCAAGCACCTCCGCCAGGTTGGGGTAGTGGGCAAATTTGTCGAGTTC
TTCGGGCCTGGAGTAGCCCAGTTGTCCATTGCTGACCGAGCTACGATTGCTAACATGTGT
CCAGAGTACGGAGCAACTGCTGCCTTTTTCCCAGTTGATGAAGTTAGTATCACGTACCTG
GTGCAAACAGGTCGTGATGAAGAAAAATTAAAGTATATTAAAAAATATCTTCAGGCTGTA
GGAATGTTTCGAGATTTCAATGACCCTTCTCAAGACCCAGACTTCACCCAGGTTGTGGAA
TTAGATTTGAAAACAGTAGTGCCTTGCTGTAGTGGACCCAAAAGGCCTCAGGACAAAGTT
GCTGTGTCCGACATGAAAAAGGACTTTGAGAGCTGCCTTGGAGCCAAGCAAGGATTTAAA
GGATTCCAAGTTGCTCCTGAACATCATAATGACCATAAGACCTTTATCTATGATAACACT
GAATTCACCCTTGCTCATGGTTCTGTGGTCATTGCTGCCATTACTAGCTGCACAAACACC
AGTAATCCGTCTGTGATGTTAGGGGCAGGATTGTTAGCAAAGAAAGCTGTGGATGCTGGC
CTGAACGTGATGCCTTACATCAAAACTAGCCTGTCTCCTGGGAGTGGCGTGGTCACCTAC
TACCTACAAGAAAGCGGAGTCATGCCTTATCTGTCTCAGCTTGGGTTTGACGTGGTGGGC
TATGGCTGCATGACCTGCATTGGCAACAGTGGGCCTTTACCTGAACCTGTGGTAGAAGCC
ATCACACAGGGAGACCTTGTAGCTGTTGGAGTACTATCTGGAAACAGGAATTTTGAAGGT
CGAGTTCACCCCAACACCCGGGCCAACTATTTAGCCTCTCCCCCCTTAGTAATAGCATAT
GCAATTGCTGGAACCATCAGAATCGACTTTGAGAAAGAGCCATTGGGAGTAAATGCAAAG
GGACAGCAGGTATTTCTGAAAGATATCTGGCCGACTAGAGACGAGATCCAGGCAGTGGAG
CGTCAGTATGTCATCCCGGGGATGTTTAAGGAAGTCTATCAGAAAATAGAGACTGTGAAT
GAAAGCTGGAATGCCTTAGCAACCCCATCAGATAAGCTGTTTTTCTGGAATTCCAAATCT
ACGTATATCAAATCACCACCATTCTTTGAAAACCTGACTTTGGATCTTCAGCCCCCTAAA
TCTATAGTGGATGCCTATGTGCTGCTAAATTTGGGAGATTCGGTAACAACTGACCACATC
TCCCCAGCTGGAAATATTGCAAGAAACAGTCCTGCTGCTCGCTACTTAACTAACAGAGGC
CTAACTCCACGAGAATTCAACTCCTATGGCTCCCGCCGAGGTAATGACGCCGTCATGGCA
CGGGGAACATTTGCCAACATTCGCTTGTTAAACAGATTTTTGAACAAGCAGGCACCACAG
ACTATCCATCTGCCTTCTGGGGAAATCCTTGATGTGTTTGATGCTGCTGAGCGGTACCAG
CAGGCAGGCCTTCCCCTGATCGTTCTGGCTGGCAAAGAGTACGGTGCAGGCAGCTCCCGA
GACTGGGCAGCTAAGGGCCCTTTCCTGCTGGGAATCAAAGCCGTCCTGGCCGAGAGCTAC
GAGCGCATTCACCGCAGTAACCTGGTTGGGATGGGTGTGATCCCACTTGAATATCTCCCT
GGTGAGAATGCAGATGCCCTGGGGCTCACAGGGCAAGAACGATACACTATCATTATTCCA
GAAAACCTCAAACCACAAATGAAAGTCCAGGTCAAGCTGGATACTGGCAAGACCTTCCAG
GCTGTCATGAGGTTTGACACTGATGTGGAGCTCACTTATTTCCTCAACGGGGGCATCCTC
AACTACATGATCCGCAAGATGGCCAAGTAG
Protein Properties
Number of Residues 889
Molecular Weight 98398.14
Theoretical pI 6.685
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Cytoplasmic aconitate hydratase
MSNPFAHLAEPLDPVQPGKKFFNLNKLEDSRYGRLPFSIRVLLEAAIRNCDEFLVKKQDI
ENILHWNVTQHKNIEVPFKPARVILQDFTGVPAVVDFAAMRDAVKKLGGDPEKINPVCPA
DLVIDHSIQVDFNRRADSLQKNQDLEFERNRERFEFLKWGSQAFHNMRIIPPGSGIIHQV
NLEYLARVVFDQDGYYYPDSLVGTDSHTTMIDGLGILGWGVGGIEAEAVMLGQPISMVLP
QVIGYRLMGKPHPLVTSTDIVLTITKHLRQVGVVGKFVEFFGPGVAQLSIADRATIANMC
PEYGATAAFFPVDEVSITYLVQTGRDEEKLKYIKKYLQAVGMFRDFNDPSQDPDFTQVVE
LDLKTVVPCCSGPKRPQDKVAVSDMKKDFESCLGAKQGFKGFQVAPEHHNDHKTFIYDNT
EFTLAHGSVVIAAITSCTNTSNPSVMLGAGLLAKKAVDAGLNVMPYIKTSLSPGSGVVTY
YLQESGVMPYLSQLGFDVVGYGCMTCIGNSGPLPEPVVEAITQGDLVAVGVLSGNRNFEG
RVHPNTRANYLASPPLVIAYAIAGTIRIDFEKEPLGVNAKGQQVFLKDIWPTRDEIQAVE
RQYVIPGMFKEVYQKIETVNESWNALATPSDKLFFWNSKSTYIKSPPFFENLTLDLQPPK
SIVDAYVLLNLGDSVTTDHISPAGNIARNSPAARYLTNRGLTPREFNSYGSRRGNDAVMA
RGTFANIRLLNRFLNKQAPQTIHLPSGEILDVFDAAERYQQAGLPLIVLAGKEYGAGSSR
DWAAKGPFLLGIKAVLAESYERIHRSNLVGMGVIPLEYLPGENADALGLTGQERYTIIIP
ENLKPQMKVQVKLDTGKTFQAVMRFDTDVELTYFLNGGILNYMIRKMAK
GenBank ID Protein 33963
UniProtKB/Swiss-Prot ID P21399
UniProtKB/Swiss-Prot Entry Name ACOC_HUMAN
PDB IDs
GenBank Gene ID Z11559
GeneCard ID ACO1
GenAtlas ID ACO1
HGNC ID HGNC:117
References
General References
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  4. Rouault TA, Tang CK, Kaptain S, Burgess WH, Haile DJ, Samaniego F, McBride OW, Harford JB, Klausner RD: Cloning of the cDNA encoding an RNA regulatory protein--the human iron-responsive element-binding protein. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7958-62. [PubMed:2172968 ]
  5. Hentze MW, Argos P: Homology between IRE-BP, a regulatory RNA-binding protein, aconitase, and isopropylmalate isomerase. Nucleic Acids Res. 1991 Apr 25;19(8):1739-40. [PubMed:1903202 ]
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  8. Vashisht AA, Zumbrennen KB, Huang X, Powers DN, Durazo A, Sun D, Bhaskaran N, Persson A, Uhlen M, Sangfelt O, Spruck C, Leibold EA, Wohlschlegel JA: Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science. 2009 Oct 30;326(5953):718-21. doi: 10.1126/science.1176333. Epub 2009 Sep 17. [PubMed:19762596 ]
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