Cytoplasmic aconitate hydratase

NameCytoplasmic aconitate hydratase
Synonyms
  • 4.2.1.3
  • Aconitase
  • Citrate hydro-lyase
  • Ferritin repressor protein
  • IRE-BP 1
  • IREB1
  • Iron regulatory protein 1
  • Iron-responsive element-binding protein 1
  • IRP1
Gene NameACO1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019695|Cytoplasmic aconitate hydratase
MSNPFAHLAEPLDPVQPGKKFFNLNKLEDSRYGRLPFSIRVLLEAAIRNCDEFLVKKQDI
ENILHWNVTQHKNIEVPFKPARVILQDFTGVPAVVDFAAMRDAVKKLGGDPEKINPVCPA
DLVIDHSIQVDFNRRADSLQKNQDLEFERNRERFEFLKWGSQAFHNMRIIPPGSGIIHQV
NLEYLARVVFDQDGYYYPDSLVGTDSHTTMIDGLGILGWGVGGIEAEAVMLGQPISMVLP
QVIGYRLMGKPHPLVTSTDIVLTITKHLRQVGVVGKFVEFFGPGVAQLSIADRATIANMC
PEYGATAAFFPVDEVSITYLVQTGRDEEKLKYIKKYLQAVGMFRDFNDPSQDPDFTQVVE
LDLKTVVPCCSGPKRPQDKVAVSDMKKDFESCLGAKQGFKGFQVAPEHHNDHKTFIYDNT
EFTLAHGSVVIAAITSCTNTSNPSVMLGAGLLAKKAVDAGLNVMPYIKTSLSPGSGVVTY
YLQESGVMPYLSQLGFDVVGYGCMTCIGNSGPLPEPVVEAITQGDLVAVGVLSGNRNFEG
RVHPNTRANYLASPPLVIAYAIAGTIRIDFEKEPLGVNAKGQQVFLKDIWPTRDEIQAVE
RQYVIPGMFKEVYQKIETVNESWNALATPSDKLFFWNSKSTYIKSPPFFENLTLDLQPPK
SIVDAYVLLNLGDSVTTDHISPAGNIARNSPAARYLTNRGLTPREFNSYGSRRGNDAVMA
RGTFANIRLLNRFLNKQAPQTIHLPSGEILDVFDAAERYQQAGLPLIVLAGKEYGAGSSR
DWAAKGPFLLGIKAVLAESYERIHRSNLVGMGVIPLEYLPGENADALGLTGQERYTIIIP
ENLKPQMKVQVKLDTGKTFQAVMRFDTDVELTYFLNGGILNYMIRKMAK
Number of residues889
Molecular Weight98398.14
Theoretical pINot Available
GO Classification
Functions
  • 4 iron, 4 sulfur cluster binding
  • iron-responsive element binding
  • RNA binding
  • metal ion binding
  • aconitate hydratase activity
Processes
  • post-embryonic development
  • citrate metabolic process
  • cellular iron ion homeostasis
  • regulation of translation
  • intestinal absorption
  • tricarboxylic acid cycle
  • response to iron(II) ion
Components
  • cytosol
  • extracellular exosome
  • cytoplasm
  • mitochondrion
  • endoplasmic reticulum
  • Golgi apparatus
General FunctionRna binding
Specific FunctionIron 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP21399
UniProtKB Entry NameACOC_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019696|Cytoplasmic aconitate hydratase (ACO1)
ATGAGCAACCCATTCGCACACCTTGCTGAGCCATTGGATCCTGTACAACCAGGAAAGAAA
TTCTTCAATTTGAATAAATTGGAGGATTCAAGATATGGGCGCTTACCATTTTCGATCAGA
GTTCTTCTGGAAGCAGCCATTCGGAATTGTGATGAGTTTTTGGTGAAGAAACAGGATATT
GAAAATATTCTACATTGGAATGTCACGCAGCACAAGAACATAGAAGTGCCATTTAAGCCT
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
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:117
Chromosome Location9
LocusNot Available
References
  1. Hirling H, Emery-Goodman A, Thompson N, Neupert B, Seiser C, Kuhn LC: Expression of active iron regulatory factor from a full-length human cDNA by in vitro transcription/translation. Nucleic Acids Res. 1992 Jan 11;20(1):33-9. 1738601
  2. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. 15164053
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 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. 1903202
  6. Kaptain S, Downey WE, Tang C, Philpott C, Haile D, Orloff DG, Harford JB, Rouault TA, Klausner RD: A regulated RNA binding protein also possesses aconitase activity. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13. 1946430
  7. Philpott CC, Klausner RD, Rouault TA: The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5. 8041788
  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. 19762596
  9. Salahudeen AA, Thompson JW, Ruiz JC, Ma HW, Kinch LN, Li Q, Grishin NV, Bruick RK: An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science. 2009 Oct 30;326(5953):722-6. doi: 10.1126/science.1176326. Epub 2009 Sep 17. 19762597
  10. Condo I, Malisan F, Guccini I, Serio D, Rufini A, Testi R: Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin. Hum Mol Genet. 2010 Apr 1;19(7):1221-9. doi: 10.1093/hmg/ddp592. Epub 2010 Jan 6. 20053667
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  13. Dupuy J, Volbeda A, Carpentier P, Darnault C, Moulis JM, Fontecilla-Camps JC: Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Structure. 2006 Jan;14(1):129-39. 16407072
  14. de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, Vulto-van Silfhout AT, Koolen DA, de Vries P, Gilissen C, del Rosario M, Hoischen A, Scheffer H, de Vries BB, Brunner HG, Veltman JA, Vissers LE: Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012 Nov 15;367(20):1921-9. doi: 10.1056/NEJMoa1206524. Epub 2012 Oct 3. 23033978