ACO1 (aconitase 1)

Gene

• Entrez ID: 48
• Gene name: Aconitase 1
• Gene symbol: ACO1
• Synonyms: ACONS, HEL60, IREB1, IREBP, IREBP1, IRP1
• Chromosome: 9
• Chromosome location: 9p21.1
• Summary: The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5` UTR of ferritin mRNA, and in the 3` UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jan 2014]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT615854	hsa-miR-208b-5p	HITS-CLIP	23824327
MIRT615855	hsa-miR-208a-5p	HITS-CLIP	23824327
MIRT615856	hsa-miR-6858-3p	HITS-CLIP	23824327
MIRT624818	hsa-miR-4503	HITS-CLIP	23824327
MIRT624819	hsa-miR-4279	HITS-CLIP	23824327
MIRT624820	hsa-miR-6792-5p	HITS-CLIP	23824327
MIRT624821	hsa-miR-6829-3p	HITS-CLIP	23824327
MIRT624822	hsa-miR-6791-3p	HITS-CLIP	23824327
MIRT624823	hsa-miR-1976	HITS-CLIP	23824327
MIRT624824	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT624825	hsa-miR-1914-5p	HITS-CLIP	23824327
MIRT624826	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT624827	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT624828	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT624829	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT624830	hsa-miR-5571-5p	HITS-CLIP	23824327
MIRT636743	hsa-miR-6807-5p	HITS-CLIP	23824327
MIRT639005	hsa-miR-8055	HITS-CLIP	23824327
MIRT639006	hsa-miR-4735-5p	HITS-CLIP	23824327
MIRT639007	hsa-miR-556-5p	HITS-CLIP	23824327

Transcription factors

Transcription factor	Regulation	Reference
MTF1	Unknown	16886906
SP1	Unknown	16886906

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003723	Function	RNA binding	IDA	1946430
GO:0003723	Function	RNA binding	NAS	1903202
GO:0003994	Function	Aconitate hydratase activity	IBA	21873635
GO:0003994	Function	Aconitate hydratase activity	IDA	1946430, 8041788
GO:0003994	Function	Aconitate hydratase activity	IMP	1281544
GO:0005515	Function	Protein binding	IPI	19762596, 19762597, 23414517
GO:0005737	Component	Cytoplasm	IMP	1281544
GO:0005737	Component	Cytoplasm	NAS	1738601
GO:0005739	Component	Mitochondrion	IBA	21873635
GO:0005739	Component	Mitochondrion	IDA
GO:0005783	Component	Endoplasmic reticulum	IDA	16144863
GO:0005794	Component	Golgi apparatus	IDA	16144863
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	IDA	16527810
GO:0005829	Component	Cytosol	TAS
GO:0006099	Process	Tricarboxylic acid cycle	IBA	21873635
GO:0006101	Process	Citrate metabolic process	IBA	21873635
GO:0006101	Process	Citrate metabolic process	IDA	8041788, 16527810
GO:0006101	Process	Citrate metabolic process	IMP	1281544
GO:0006417	Process	Regulation of translation	IEA
GO:0006879	Process	Cellular iron ion homeostasis	TAS
GO:0009791	Process	Post-embryonic development	IEA
GO:0010040	Process	Response to iron(II) ion	IDA	8041788
GO:0030350	Function	Iron-responsive element binding	IBA	21873635
GO:0030350	Function	Iron-responsive element binding	IDA	8041788
GO:0030350	Function	Iron-responsive element binding	IMP	1281544, 23891004
GO:0046872	Function	Metal ion binding	IEA
GO:0047780	Function	Citrate dehydratase activity	IEA
GO:0050892	Process	Intestinal absorption	IEA
GO:0051538	Function	3 iron, 4 sulfur cluster binding	IBA	21873635
GO:0051538	Function	3 iron, 4 sulfur cluster binding	IMP	1281544
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IBA	21873635
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IDA	16407072
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IMP	1281544
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145

Other IDs

• MIM: 100880
• HGNC: 117
• e!Ensembl: ENSG00000122729

Protein

• UniProt ID: P21399
• Protein name: Cytoplasmic aconitate hydratase (Aconitase) (EC 4.2.1.3) (Citrate hydro-lyase) (Ferritin repressor protein) (Iron regulatory protein 1) (IRP1) (Iron-responsive element-binding protein 1) (IRE-BP 1)
• Protein 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.
• PDB: 2B3X, 2B3Y
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00330	Aconitase	59 → 564	Aconitase family (aconitate hydratase)	Family
  PF00694	Aconitase_C	692 → 821	Aconitase C-terminal domain	Domain

• Sequence:

  MSNPFAHLAEPLDPVQPGKKFFNLNKLEDSRYGRLPFSIRVLLEAAIRNCDEFLVKKQDI
  ENILHWNVTQHKNIEVPFKPARVILQDFTGVPAVVDFAAMRDAVKKLGGDPEKINPVCPA
  DLVIDHSIQVDFNRRADSLQKNQDLEFERNRERFEFLKWGSQAFHNMRIIPPGSGIIHQV
  NLEYLARVVFDQDGYYYPDSLVGTDSHTTMIDGLGILGWGVGGIEAEAVMLGQPISMVLP
  QVIGYRLMGKPHPLVTSTDIVLTITKHLRQVGVVGKFVEFFGPGVAQLSIADRATIANMC
  PEYGATAAFFPVDEVSITYLVQTGRDEEKLKYIKKYLQAVGMFRDFNDPSQDPDFTQVVE
  LDLKTVVPCCSGPKRPQDKVAVSDMKKDFESCLGAKQGFKGFQVAPEHHNDHKTFIYDNT
  EFTLAHGSVVIAAITSCTNTSNPSVMLGAGLLAKKAVDAGLNVMPYIKTSLSPGSGVVTY
  YLQESGVMPYLSQLGFDVVGYGCMTCIGNSGPLPEPVVEAITQGDLVAVGVLSGNRNFEG
  RVHPNTRANYLASPPLVIAYAIAGTIRIDFEKEPLGVNAKGQQVFLKDIWPTRDEIQAVE
  RQYVIPGMFKEVYQKIETVNESWNALATPSDKLFFWNSKSTYIKSPPFFENLTLDLQPPK
  SIVDAYVLLNLGDSVTTDHISPAGNIARNSPAARYLTNRGLTPREFNSYGSRRGNDAVMA
  RGTFANIRLLNRFLNKQAPQTIHLPSGEILDVFDAAERYQQAGLPLIVLAGKEYGAGSSR
  DWAAKGPFLLGIKAVLAESYERIHRSNLVGMGVIPLEYLPGENADALGLTGQERYTIIIP
  ENLKPQMKVQVKLDTGKTFQAVMRFDTDVELTYFLNGGILNYMIRKMAK

• Sequence length: 889