ACO1

Protein identityUniProt · HPA

UniProt accession

P21399

Gene

ACO1

Ensembl

ENSG00000122729

Chromosome

9

Canonical length

889 aa

Protein class

Cancer-related genes, Citric acid cycle related proteins, Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Mitochondria,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

889 residues, UniProt reviewed canonical sequence.

>P21399|ACO1
     1  MSNPFAHLAE PLDPVQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAIRNC DEFLVKKQDI
    61  ENILHWNVTQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGD PEKINPVCPA
   121  DLVIDHSIQV DFNRRADSLQ KNQDLEFERN RERFEFLKWG SQAFHNMRII PPGSGIIHQV
   181  NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGILGWG VGGIEAEAVM LGQPISMVLP
   241  QVIGYRLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC
   301  PEYGATAAFF PVDEVSITYL VQTGRDEEKL KYIKKYLQAV GMFRDFNDPS QDPDFTQVVE
   361  LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPEHHN DHKTFIYDNT
   421  EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LNVMPYIKTS LSPGSGVVTY
   481  YLQESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG
   541  RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE
   601  RQYVIPGMFK EVYQKIETVN ESWNALATPS DKLFFWNSKS TYIKSPPFFE NLTLDLQPPK
   661  SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAVMA
   721  RGTFANIRLL NRFLNKQAPQ TIHLPSGEIL DVFDAAERYQ QAGLPLIVLA GKEYGAGSSR
   781  DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GENADALGLT GQERYTIIIP
   841  ENLKPQMKVQ VKLDTGKTFQ AVMRFDTDVE LTYFLNGGIL NYMIRKMAK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACO1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.19

Highest tissue expression

126 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.93

gnomAD pLI

0

gnomAD missense Z

0.92

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• citrate metabolic process
• intestinal absorption
• intracellular iron ion homeostasis
• NADPH regeneration
• post-embryonic development
• response to iron(II) ion
• tricarboxylic acid cycle

Molecular functions

• 3 iron, 4 sulfur cluster binding
• 4 iron, 4 sulfur cluster binding
• aconitate hydratase activity
• iron-responsive element binding
• iron-sulfur cluster binding
• metal ion binding
• mRNA regulatory element binding translation repressor activity
• RNA binding

Cellular components

• cytoplasm
• cytosol
• endoplasmic reticulum
• extracellular exosome
• Golgi apparatus
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
• Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
• Aconitase/Iron-responsive element-binding protein 2
• Aconitase/3-isopropylmalate dehydratase, swivel
• Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
• Aconitase family, 4Fe-4S cluster binding site
• Aconitase, iron-sulfur domain
• Aconitase A, swivel domain
• Aconitase family (aconitate hydratase)
• Aconitase C-terminal domain

KeywordsUniProt

• 4Fe-4S
• Cytoplasm
• Iron
• Iron-sulfur
• Lyase
• Metal-binding
• Phosphoprotein
• RNA-binding
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of ACO1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FXN
• SGCG