Full text data of ACO1
ACO1
(IREB1)
[Confidence: low (only semi-automatic identification from reviews)]
Cytoplasmic aconitate hydratase; Aconitase; 4.2.1.3 (Citrate hydro-lyase; Ferritin repressor protein; Iron regulatory protein 1; IRP1; Iron-responsive element-binding protein 1; IRE-BP 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cytoplasmic aconitate hydratase; Aconitase; 4.2.1.3 (Citrate hydro-lyase; Ferritin repressor protein; Iron regulatory protein 1; IRP1; Iron-responsive element-binding protein 1; IRE-BP 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P21399
ID ACOC_HUMAN Reviewed; 889 AA.
AC P21399; D3DRK7; Q14652; Q5VZA7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 3.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Cytoplasmic aconitate hydratase;
DE Short=Aconitase;
DE EC=4.2.1.3;
DE AltName: Full=Citrate hydro-lyase;
DE AltName: Full=Ferritin repressor protein;
DE AltName: Full=Iron regulatory protein 1;
DE Short=IRP1;
DE AltName: Full=Iron-responsive element-binding protein 1;
DE Short=IRE-BP 1;
GN Name=ACO1; Synonyms=IREB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1738601; DOI=10.1093/nar/20.1.33;
RA Hirling H., Emery-Goodman A., Thompson N., Neupert B., Seiser C.,
RA Kuehn L.;
RT "Expression of active iron regulatory factor from a full-length human
RT cDNA by in vitro transcription/translation.";
RL Nucleic Acids Res. 20:33-39(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 74-889, RNA-BINDING, AND PARTIAL PROTEIN
RP SEQUENCE.
RX PubMed=2172968; DOI=10.1073/pnas.87.20.7958;
RA Rouault T.A., Tang C.K., Kaptain S., Burgess W.H., Haile D.J.,
RA Samaniego F., McBride O.W., Harford J.B., Klausner R.D.;
RT "Cloning of the cDNA encoding an RNA regulatory protein -- the human
RT iron-responsive element-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:7958-7962(1990).
RN [7]
RP SIMILARITY TO ACONITASES AND IPM ISOMERASES.
RX PubMed=1903202; DOI=10.1093/nar/19.8.1739;
RA Hentze M.W., Argos P.;
RT "Homology between IRE-BP, a regulatory RNA-binding protein, aconitase,
RT and isopropylmalate isomerase.";
RL Nucleic Acids Res. 19:1739-1740(1991).
RN [8]
RP FUNCTION AS AN ACONITASE.
RX PubMed=1946430; DOI=10.1073/pnas.88.22.10109;
RA Kaptain S., Downey W.E., Tang C.K., Philpott C., Haile D.J.,
RA Orloff D.G., Harford J.B., Rouault T.A., Klausner R.D.;
RT "A regulated RNA binding protein also possesses aconitase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10109-10113(1991).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF CYS-300; CYS-437; CYS-503; CYS-506;
RP ARG-536; ARG-541; ARG-699; SER-778 AND ARG-780.
RX PubMed=8041788; DOI=10.1073/pnas.91.15.7321;
RA Philpott C.C., Klausner R.D., Rouault T.A.;
RT "The bifunctional iron-responsive element binding protein/cytosolic
RT aconitase: the role of active-site residues in ligand binding and
RT regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7321-7325(1994).
RN [10]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=19762596; DOI=10.1126/science.1176333;
RA Vashisht A.A., Zumbrennen K.B., Huang X., Powers D.N., Durazo A.,
RA Sun D., Bhaskaran N., Persson A., Uhlen M., Sangfelt O., Spruck C.,
RA Leibold E.A., Wohlschlegel J.A.;
RT "Control of iron homeostasis by an iron-regulated ubiquitin ligase.";
RL Science 326:718-721(2009).
RN [11]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=19762597; DOI=10.1126/science.1176326;
RA Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.-W., Kinch L.N.,
RA Li Q., Grishin N.V., Bruick R.K.;
RT "An E3 ligase possessing an iron responsive hemerythrin domain is a
RT regulator of iron homeostasis.";
RL Science 326:722-726(2009).
RN [12]
RP INTERACTION WITH FRATAXIN(81-210).
RX PubMed=20053667; DOI=10.1093/hmg/ddp592;
RA Condo I., Malisan F., Guccini I., Serio D., Rufini A., Testi R.;
RT "Molecular control of the cytosolic aconitase/IRP1 switch by
RT extramitochondrial frataxin.";
RL Hum. Mol. Genet. 19:1221-1229(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP CLUSTER, AND COFACTOR.
RX PubMed=16407072; DOI=10.1016/j.str.2005.09.009;
RA Dupuy J., Volbeda A., Carpentier P., Darnault C., Moulis J.-M.,
RA Fontecilla-Camps J.C.;
RT "Crystal structure of human iron regulatory protein 1 as cytosolic
RT aconitase.";
RL Structure 14:129-139(2006).
RN [15]
RP VARIANT MET-318.
RX PubMed=23033978; DOI=10.1056/NEJMoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P.,
RA Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA Brunner H.G., Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Iron sensor. Binds a 4Fe-4S cluster and functions as
CC aconitase when cellular iron levels are high. Functions as mRNA
CC binding protein that regulates uptake, sequestration and
CC utilization of iron when cellular iron levels are low. Binds to
CC iron-responsive elements (IRES) in target mRNA species when iron
CC levels are low. Binding of a 4Fe-4S cluster precludes RNA binding.
CC -!- FUNCTION: Catalyzes the isomerization of citrate to isocitrate via
CC cis-aconitate (By similarity).
CC -!- CATALYTIC ACTIVITY: Citrate = isocitrate.
CC -!- COFACTOR: Binds 1 4Fe-4S cluster per subunit.
CC -!- SUBUNIT: Interacts (when associated with the 4Fe-4S) with FBXL5.
CC Interacts with frataxin(81-210).
CC -!- INTERACTION:
CC P20929:NEB; NbExp=2; IntAct=EBI-2847111, EBI-1049657;
CC Q13326:SGCG; NbExp=2; IntAct=EBI-2847111, EBI-5357343;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Aconitase entry;
CC URL="http://en.wikipedia.org/wiki/Aconitase";
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DR EMBL; Z11559; CAA77651.1; -; mRNA.
DR EMBL; DQ496106; ABF47095.1; -; Genomic_DNA.
DR EMBL; AL161783; CAH72598.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58549.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58550.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58552.1; -; Genomic_DNA.
DR EMBL; BC018103; AAH18103.1; -; mRNA.
DR EMBL; M58510; AAA69900.1; -; mRNA.
DR PIR; S26403; S26403.
DR RefSeq; NP_001265281.1; NM_001278352.1.
DR RefSeq; NP_002188.1; NM_002197.2.
DR RefSeq; XP_005251533.1; XM_005251476.1.
DR RefSeq; XP_005251534.1; XM_005251477.1.
DR UniGene; Hs.567229; -.
DR PDB; 2B3X; X-ray; 2.54 A; A=2-889.
DR PDB; 2B3Y; X-ray; 1.85 A; A/B=2-889.
DR PDBsum; 2B3X; -.
DR PDBsum; 2B3Y; -.
DR ProteinModelPortal; P21399; -.
DR SMR; P21399; 2-889.
DR IntAct; P21399; 8.
DR STRING; 9606.ENSP00000309477; -.
DR PhosphoSite; P21399; -.
DR DMDM; 3123225; -.
DR REPRODUCTION-2DPAGE; IPI00008485; -.
DR UCD-2DPAGE; P21399; -.
DR PaxDb; P21399; -.
DR PeptideAtlas; P21399; -.
DR PRIDE; P21399; -.
DR Ensembl; ENST00000309951; ENSP00000309477; ENSG00000122729.
DR Ensembl; ENST00000379923; ENSP00000369255; ENSG00000122729.
DR GeneID; 48; -.
DR KEGG; hsa:48; -.
DR UCSC; uc003zqw.4; human.
DR CTD; 48; -.
DR GeneCards; GC09P032374; -.
DR HGNC; HGNC:117; ACO1.
DR HPA; HPA019371; -.
DR HPA; HPA024157; -.
DR MIM; 100880; gene.
DR neXtProt; NX_P21399; -.
DR PharmGKB; PA24442; -.
DR eggNOG; COG1048; -.
DR HOGENOM; HOG000025704; -.
DR HOVERGEN; HBG052147; -.
DR InParanoid; P21399; -.
DR KO; K01681; -.
DR OMA; SVMMAAG; -.
DR OrthoDB; EOG7CG6Z7; -.
DR PhylomeDB; P21399; -.
DR BioCyc; MetaCyc:HS04597-MONOMER; -.
DR EvolutionaryTrace; P21399; -.
DR GenomeRNAi; 48; -.
DR NextBio; 187; -.
DR PRO; PR:P21399; -.
DR ArrayExpress; P21399; -.
DR Bgee; P21399; -.
DR CleanEx; HS_ACO1; -.
DR Genevestigator; P21399; -.
DR GO; GO:0005829; C:cytosol; IDA:HGNC.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:UniProtKB.
DR GO; GO:0030350; F:iron-responsive element binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0006101; P:citrate metabolic process; IDA:UniProtKB.
DR GO; GO:0050892; P:intestinal absorption; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006417; P:regulation of translation; IEA:Ensembl.
DR GO; GO:0010040; P:response to iron(II) ion; IDA:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 3.
DR Gene3D; 3.40.1060.10; -; 1.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR015937; Acoase/IPM_deHydtase.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR006249; Aconitase/Fe_reg_prot_2.
DR InterPro; IPR015934; Aconitase/Fe_reg_prot_2/AcnD.
DR InterPro; IPR015932; Aconitase/IPMdHydase_lsu_aba_2.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR PANTHER; PTHR11670; PTHR11670; 1.
DR PANTHER; PTHR11670:SF1; PTHR11670:SF1; 1.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF52016; SSF52016; 1.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01341; aconitase_1; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Iron; Iron-sulfur; Lyase; Metal-binding;
KW Polymorphism; Reference proteome; RNA-binding;
KW Tricarboxylic acid cycle.
FT CHAIN 1 889 Cytoplasmic aconitate hydratase.
FT /FTId=PRO_0000076680.
FT REGION 205 207 Substrate binding (By similarity).
FT REGION 779 780 Substrate binding (By similarity).
FT METAL 437 437 Iron-sulfur (4Fe-4S) (By similarity).
FT METAL 503 503 Iron-sulfur (4Fe-4S) (By similarity).
FT METAL 506 506 Iron-sulfur (4Fe-4S) (By similarity).
FT BINDING 86 86 Substrate (By similarity).
FT BINDING 536 536 Substrate (By similarity).
FT BINDING 541 541 Substrate (By similarity).
FT BINDING 699 699 Substrate (By similarity).
FT VARIANT 318 318 T -> M.
FT /FTId=VAR_069413.
FT VARIANT 395 395 A -> D (in dbSNP:rs3814519).
FT /FTId=VAR_048180.
FT VARIANT 486 486 G -> R (in dbSNP:rs34630459).
FT /FTId=VAR_048181.
FT MUTAGEN 300 300 C->S: No effect on aconitase activity or
FT on RNA binding.
FT MUTAGEN 437 437 C->S: Loss of aconitase activity. Leads
FT to constitutive RNA binding, irrespective
FT of iron levels.
FT MUTAGEN 503 503 C->S: Loss of aconitase activity. Leads
FT to constitutive RNA binding, irrespective
FT of iron levels.
FT MUTAGEN 506 506 C->S: Loss of aconitase activity. Leads
FT of iron levels.
FT MUTAGEN 536 536 R->Q: Strongly reduced RNA binding.
FT MUTAGEN 541 541 R->Q: Strongly reduced RNA binding.
FT MUTAGEN 699 699 R->K: No effect on RNA binding.
FT MUTAGEN 778 778 S->A: No effect on iron-regulated RNA
FT binding. Loss of aconitase activity.
FT MUTAGEN 780 780 R->Q: Nearly abolishes RNA binding.
FT HELIX 6 8
FT STRAND 9 12
FT STRAND 20 22
FT HELIX 24 27
FT HELIX 32 34
FT HELIX 37 48
FT STRAND 52 55
FT HELIX 57 64
FT HELIX 66 69
FT TURN 70 73
FT STRAND 75 78
FT STRAND 81 86
FT HELIX 87 106
FT HELIX 111 113
FT STRAND 120 123
FT HELIX 138 163
FT STRAND 167 170
FT HELIX 177 183
FT STRAND 188 192
FT STRAND 195 198
FT STRAND 200 205
FT HELIX 206 214
FT STRAND 217 220
FT HELIX 223 230
FT STRAND 235 238
FT STRAND 242 249
FT HELIX 257 271
FT STRAND 277 282
FT HELIX 283 285
FT HELIX 290 298
FT HELIX 300 303
FT STRAND 306 309
FT HELIX 314 322
FT HELIX 327 340
FT HELIX 349 351
FT STRAND 356 362
FT HELIX 363 365
FT STRAND 368 371
FT STRAND 379 381
FT HELIX 382 384
FT HELIX 385 394
FT HELIX 406 408
FT STRAND 412 417
FT STRAND 420 425
FT STRAND 428 434
FT HELIX 437 440
FT HELIX 443 458
FT STRAND 467 471
FT HELIX 476 484
FT HELIX 488 493
FT STRAND 501 503
FT HELIX 504 507
FT HELIX 515 524
FT STRAND 529 535
FT TURN 539 541
FT STRAND 547 551
FT HELIX 554 563
FT STRAND 564 566
FT TURN 570 572
FT STRAND 575 578
FT TURN 579 581
FT STRAND 582 584
FT HELIX 586 589
FT HELIX 593 603
FT HELIX 606 613
FT TURN 614 618
FT HELIX 621 625
FT HELIX 647 649
FT STRAND 662 671
FT HELIX 677 680
FT STRAND 688 690
FT HELIX 691 698
FT HELIX 703 705
FT HELIX 710 712
FT HELIX 716 721
FT TURN 722 724
FT TURN 732 734
FT STRAND 735 737
FT STRAND 739 742
FT TURN 744 746
FT STRAND 749 751
FT HELIX 752 761
FT STRAND 766 769
FT STRAND 772 774
FT HELIX 782 789
FT STRAND 792 798
FT HELIX 802 810
FT STRAND 814 818
FT HELIX 824 827
FT STRAND 835 837
FT STRAND 848 853
FT STRAND 858 863
FT HELIX 868 876
FT HELIX 879 888
SQ SEQUENCE 889 AA; 98399 MW; E1A05AF701D46DCB CRC64;
MSNPFAHLAE PLDPVQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAIRNC DEFLVKKQDI
ENILHWNVTQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGD PEKINPVCPA
DLVIDHSIQV DFNRRADSLQ KNQDLEFERN RERFEFLKWG SQAFHNMRII PPGSGIIHQV
NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGILGWG VGGIEAEAVM LGQPISMVLP
QVIGYRLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC
PEYGATAAFF PVDEVSITYL VQTGRDEEKL KYIKKYLQAV GMFRDFNDPS QDPDFTQVVE
LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPEHHN DHKTFIYDNT
EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LNVMPYIKTS LSPGSGVVTY
YLQESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG
RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE
RQYVIPGMFK EVYQKIETVN ESWNALATPS DKLFFWNSKS TYIKSPPFFE NLTLDLQPPK
SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAVMA
RGTFANIRLL NRFLNKQAPQ TIHLPSGEIL DVFDAAERYQ QAGLPLIVLA GKEYGAGSSR
DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GENADALGLT GQERYTIIIP
ENLKPQMKVQ VKLDTGKTFQ AVMRFDTDVE LTYFLNGGIL NYMIRKMAK
//
ID ACOC_HUMAN Reviewed; 889 AA.
AC P21399; D3DRK7; Q14652; Q5VZA7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 3.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Cytoplasmic aconitate hydratase;
DE Short=Aconitase;
DE EC=4.2.1.3;
DE AltName: Full=Citrate hydro-lyase;
DE AltName: Full=Ferritin repressor protein;
DE AltName: Full=Iron regulatory protein 1;
DE Short=IRP1;
DE AltName: Full=Iron-responsive element-binding protein 1;
DE Short=IRE-BP 1;
GN Name=ACO1; Synonyms=IREB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1738601; DOI=10.1093/nar/20.1.33;
RA Hirling H., Emery-Goodman A., Thompson N., Neupert B., Seiser C.,
RA Kuehn L.;
RT "Expression of active iron regulatory factor from a full-length human
RT cDNA by in vitro transcription/translation.";
RL Nucleic Acids Res. 20:33-39(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 74-889, RNA-BINDING, AND PARTIAL PROTEIN
RP SEQUENCE.
RX PubMed=2172968; DOI=10.1073/pnas.87.20.7958;
RA Rouault T.A., Tang C.K., Kaptain S., Burgess W.H., Haile D.J.,
RA Samaniego F., McBride O.W., Harford J.B., Klausner R.D.;
RT "Cloning of the cDNA encoding an RNA regulatory protein -- the human
RT iron-responsive element-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:7958-7962(1990).
RN [7]
RP SIMILARITY TO ACONITASES AND IPM ISOMERASES.
RX PubMed=1903202; DOI=10.1093/nar/19.8.1739;
RA Hentze M.W., Argos P.;
RT "Homology between IRE-BP, a regulatory RNA-binding protein, aconitase,
RT and isopropylmalate isomerase.";
RL Nucleic Acids Res. 19:1739-1740(1991).
RN [8]
RP FUNCTION AS AN ACONITASE.
RX PubMed=1946430; DOI=10.1073/pnas.88.22.10109;
RA Kaptain S., Downey W.E., Tang C.K., Philpott C., Haile D.J.,
RA Orloff D.G., Harford J.B., Rouault T.A., Klausner R.D.;
RT "A regulated RNA binding protein also possesses aconitase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10109-10113(1991).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF CYS-300; CYS-437; CYS-503; CYS-506;
RP ARG-536; ARG-541; ARG-699; SER-778 AND ARG-780.
RX PubMed=8041788; DOI=10.1073/pnas.91.15.7321;
RA Philpott C.C., Klausner R.D., Rouault T.A.;
RT "The bifunctional iron-responsive element binding protein/cytosolic
RT aconitase: the role of active-site residues in ligand binding and
RT regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7321-7325(1994).
RN [10]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=19762596; DOI=10.1126/science.1176333;
RA Vashisht A.A., Zumbrennen K.B., Huang X., Powers D.N., Durazo A.,
RA Sun D., Bhaskaran N., Persson A., Uhlen M., Sangfelt O., Spruck C.,
RA Leibold E.A., Wohlschlegel J.A.;
RT "Control of iron homeostasis by an iron-regulated ubiquitin ligase.";
RL Science 326:718-721(2009).
RN [11]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=19762597; DOI=10.1126/science.1176326;
RA Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.-W., Kinch L.N.,
RA Li Q., Grishin N.V., Bruick R.K.;
RT "An E3 ligase possessing an iron responsive hemerythrin domain is a
RT regulator of iron homeostasis.";
RL Science 326:722-726(2009).
RN [12]
RP INTERACTION WITH FRATAXIN(81-210).
RX PubMed=20053667; DOI=10.1093/hmg/ddp592;
RA Condo I., Malisan F., Guccini I., Serio D., Rufini A., Testi R.;
RT "Molecular control of the cytosolic aconitase/IRP1 switch by
RT extramitochondrial frataxin.";
RL Hum. Mol. Genet. 19:1221-1229(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP CLUSTER, AND COFACTOR.
RX PubMed=16407072; DOI=10.1016/j.str.2005.09.009;
RA Dupuy J., Volbeda A., Carpentier P., Darnault C., Moulis J.-M.,
RA Fontecilla-Camps J.C.;
RT "Crystal structure of human iron regulatory protein 1 as cytosolic
RT aconitase.";
RL Structure 14:129-139(2006).
RN [15]
RP VARIANT MET-318.
RX PubMed=23033978; DOI=10.1056/NEJMoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P.,
RA Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA Brunner H.G., Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Iron sensor. Binds a 4Fe-4S cluster and functions as
CC aconitase when cellular iron levels are high. Functions as mRNA
CC binding protein that regulates uptake, sequestration and
CC utilization of iron when cellular iron levels are low. Binds to
CC iron-responsive elements (IRES) in target mRNA species when iron
CC levels are low. Binding of a 4Fe-4S cluster precludes RNA binding.
CC -!- FUNCTION: Catalyzes the isomerization of citrate to isocitrate via
CC cis-aconitate (By similarity).
CC -!- CATALYTIC ACTIVITY: Citrate = isocitrate.
CC -!- COFACTOR: Binds 1 4Fe-4S cluster per subunit.
CC -!- SUBUNIT: Interacts (when associated with the 4Fe-4S) with FBXL5.
CC Interacts with frataxin(81-210).
CC -!- INTERACTION:
CC P20929:NEB; NbExp=2; IntAct=EBI-2847111, EBI-1049657;
CC Q13326:SGCG; NbExp=2; IntAct=EBI-2847111, EBI-5357343;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Aconitase entry;
CC URL="http://en.wikipedia.org/wiki/Aconitase";
CC -----------------------------------------------------------------------
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DR EMBL; Z11559; CAA77651.1; -; mRNA.
DR EMBL; DQ496106; ABF47095.1; -; Genomic_DNA.
DR EMBL; AL161783; CAH72598.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58549.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58550.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58552.1; -; Genomic_DNA.
DR EMBL; BC018103; AAH18103.1; -; mRNA.
DR EMBL; M58510; AAA69900.1; -; mRNA.
DR PIR; S26403; S26403.
DR RefSeq; NP_001265281.1; NM_001278352.1.
DR RefSeq; NP_002188.1; NM_002197.2.
DR RefSeq; XP_005251533.1; XM_005251476.1.
DR RefSeq; XP_005251534.1; XM_005251477.1.
DR UniGene; Hs.567229; -.
DR PDB; 2B3X; X-ray; 2.54 A; A=2-889.
DR PDB; 2B3Y; X-ray; 1.85 A; A/B=2-889.
DR PDBsum; 2B3X; -.
DR PDBsum; 2B3Y; -.
DR ProteinModelPortal; P21399; -.
DR SMR; P21399; 2-889.
DR IntAct; P21399; 8.
DR STRING; 9606.ENSP00000309477; -.
DR PhosphoSite; P21399; -.
DR DMDM; 3123225; -.
DR REPRODUCTION-2DPAGE; IPI00008485; -.
DR UCD-2DPAGE; P21399; -.
DR PaxDb; P21399; -.
DR PeptideAtlas; P21399; -.
DR PRIDE; P21399; -.
DR Ensembl; ENST00000309951; ENSP00000309477; ENSG00000122729.
DR Ensembl; ENST00000379923; ENSP00000369255; ENSG00000122729.
DR GeneID; 48; -.
DR KEGG; hsa:48; -.
DR UCSC; uc003zqw.4; human.
DR CTD; 48; -.
DR GeneCards; GC09P032374; -.
DR HGNC; HGNC:117; ACO1.
DR HPA; HPA019371; -.
DR HPA; HPA024157; -.
DR MIM; 100880; gene.
DR neXtProt; NX_P21399; -.
DR PharmGKB; PA24442; -.
DR eggNOG; COG1048; -.
DR HOGENOM; HOG000025704; -.
DR HOVERGEN; HBG052147; -.
DR InParanoid; P21399; -.
DR KO; K01681; -.
DR OMA; SVMMAAG; -.
DR OrthoDB; EOG7CG6Z7; -.
DR PhylomeDB; P21399; -.
DR BioCyc; MetaCyc:HS04597-MONOMER; -.
DR EvolutionaryTrace; P21399; -.
DR GenomeRNAi; 48; -.
DR NextBio; 187; -.
DR PRO; PR:P21399; -.
DR ArrayExpress; P21399; -.
DR Bgee; P21399; -.
DR CleanEx; HS_ACO1; -.
DR Genevestigator; P21399; -.
DR GO; GO:0005829; C:cytosol; IDA:HGNC.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:UniProtKB.
DR GO; GO:0030350; F:iron-responsive element binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0006101; P:citrate metabolic process; IDA:UniProtKB.
DR GO; GO:0050892; P:intestinal absorption; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006417; P:regulation of translation; IEA:Ensembl.
DR GO; GO:0010040; P:response to iron(II) ion; IDA:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 3.
DR Gene3D; 3.40.1060.10; -; 1.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR015937; Acoase/IPM_deHydtase.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR006249; Aconitase/Fe_reg_prot_2.
DR InterPro; IPR015934; Aconitase/Fe_reg_prot_2/AcnD.
DR InterPro; IPR015932; Aconitase/IPMdHydase_lsu_aba_2.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR PANTHER; PTHR11670; PTHR11670; 1.
DR PANTHER; PTHR11670:SF1; PTHR11670:SF1; 1.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF52016; SSF52016; 1.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01341; aconitase_1; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Iron; Iron-sulfur; Lyase; Metal-binding;
KW Polymorphism; Reference proteome; RNA-binding;
KW Tricarboxylic acid cycle.
FT CHAIN 1 889 Cytoplasmic aconitate hydratase.
FT /FTId=PRO_0000076680.
FT REGION 205 207 Substrate binding (By similarity).
FT REGION 779 780 Substrate binding (By similarity).
FT METAL 437 437 Iron-sulfur (4Fe-4S) (By similarity).
FT METAL 503 503 Iron-sulfur (4Fe-4S) (By similarity).
FT METAL 506 506 Iron-sulfur (4Fe-4S) (By similarity).
FT BINDING 86 86 Substrate (By similarity).
FT BINDING 536 536 Substrate (By similarity).
FT BINDING 541 541 Substrate (By similarity).
FT BINDING 699 699 Substrate (By similarity).
FT VARIANT 318 318 T -> M.
FT /FTId=VAR_069413.
FT VARIANT 395 395 A -> D (in dbSNP:rs3814519).
FT /FTId=VAR_048180.
FT VARIANT 486 486 G -> R (in dbSNP:rs34630459).
FT /FTId=VAR_048181.
FT MUTAGEN 300 300 C->S: No effect on aconitase activity or
FT on RNA binding.
FT MUTAGEN 437 437 C->S: Loss of aconitase activity. Leads
FT to constitutive RNA binding, irrespective
FT of iron levels.
FT MUTAGEN 503 503 C->S: Loss of aconitase activity. Leads
FT to constitutive RNA binding, irrespective
FT of iron levels.
FT MUTAGEN 506 506 C->S: Loss of aconitase activity. Leads
FT of iron levels.
FT MUTAGEN 536 536 R->Q: Strongly reduced RNA binding.
FT MUTAGEN 541 541 R->Q: Strongly reduced RNA binding.
FT MUTAGEN 699 699 R->K: No effect on RNA binding.
FT MUTAGEN 778 778 S->A: No effect on iron-regulated RNA
FT binding. Loss of aconitase activity.
FT MUTAGEN 780 780 R->Q: Nearly abolishes RNA binding.
FT HELIX 6 8
FT STRAND 9 12
FT STRAND 20 22
FT HELIX 24 27
FT HELIX 32 34
FT HELIX 37 48
FT STRAND 52 55
FT HELIX 57 64
FT HELIX 66 69
FT TURN 70 73
FT STRAND 75 78
FT STRAND 81 86
FT HELIX 87 106
FT HELIX 111 113
FT STRAND 120 123
FT HELIX 138 163
FT STRAND 167 170
FT HELIX 177 183
FT STRAND 188 192
FT STRAND 195 198
FT STRAND 200 205
FT HELIX 206 214
FT STRAND 217 220
FT HELIX 223 230
FT STRAND 235 238
FT STRAND 242 249
FT HELIX 257 271
FT STRAND 277 282
FT HELIX 283 285
FT HELIX 290 298
FT HELIX 300 303
FT STRAND 306 309
FT HELIX 314 322
FT HELIX 327 340
FT HELIX 349 351
FT STRAND 356 362
FT HELIX 363 365
FT STRAND 368 371
FT STRAND 379 381
FT HELIX 382 384
FT HELIX 385 394
FT HELIX 406 408
FT STRAND 412 417
FT STRAND 420 425
FT STRAND 428 434
FT HELIX 437 440
FT HELIX 443 458
FT STRAND 467 471
FT HELIX 476 484
FT HELIX 488 493
FT STRAND 501 503
FT HELIX 504 507
FT HELIX 515 524
FT STRAND 529 535
FT TURN 539 541
FT STRAND 547 551
FT HELIX 554 563
FT STRAND 564 566
FT TURN 570 572
FT STRAND 575 578
FT TURN 579 581
FT STRAND 582 584
FT HELIX 586 589
FT HELIX 593 603
FT HELIX 606 613
FT TURN 614 618
FT HELIX 621 625
FT HELIX 647 649
FT STRAND 662 671
FT HELIX 677 680
FT STRAND 688 690
FT HELIX 691 698
FT HELIX 703 705
FT HELIX 710 712
FT HELIX 716 721
FT TURN 722 724
FT TURN 732 734
FT STRAND 735 737
FT STRAND 739 742
FT TURN 744 746
FT STRAND 749 751
FT HELIX 752 761
FT STRAND 766 769
FT STRAND 772 774
FT HELIX 782 789
FT STRAND 792 798
FT HELIX 802 810
FT STRAND 814 818
FT HELIX 824 827
FT STRAND 835 837
FT STRAND 848 853
FT STRAND 858 863
FT HELIX 868 876
FT HELIX 879 888
SQ SEQUENCE 889 AA; 98399 MW; E1A05AF701D46DCB CRC64;
MSNPFAHLAE PLDPVQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAIRNC DEFLVKKQDI
ENILHWNVTQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGD PEKINPVCPA
DLVIDHSIQV DFNRRADSLQ KNQDLEFERN RERFEFLKWG SQAFHNMRII PPGSGIIHQV
NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGILGWG VGGIEAEAVM LGQPISMVLP
QVIGYRLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC
PEYGATAAFF PVDEVSITYL VQTGRDEEKL KYIKKYLQAV GMFRDFNDPS QDPDFTQVVE
LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPEHHN DHKTFIYDNT
EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LNVMPYIKTS LSPGSGVVTY
YLQESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG
RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE
RQYVIPGMFK EVYQKIETVN ESWNALATPS DKLFFWNSKS TYIKSPPFFE NLTLDLQPPK
SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAVMA
RGTFANIRLL NRFLNKQAPQ TIHLPSGEIL DVFDAAERYQ QAGLPLIVLA GKEYGAGSSR
DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GENADALGLT GQERYTIIIP
ENLKPQMKVQ VKLDTGKTFQ AVMRFDTDVE LTYFLNGGIL NYMIRKMAK
//
MIM
100880
*RECORD*
*FIELD* NO
100880
*FIELD* TI
*100880 ACONITASE 1, SOLUBLE; ACO1
;;ACONITATE HYDRATASE, SOLUBLE;;
ACONITASE, SOLUBLE; ACONS;;
read moreIRON-RESPONSIVE ELEMENT-BINDING PROTEIN 1; IREB1;;
IRE-BINDING PROTEIN 1; IREBP1; IREBP;;
IRON REGULATORY PROTEIN 1; IRP1
*FIELD* TX
DESCRIPTION
Soluble aconitase is a bifunctional protein with mutually exclusive
functions as an iron responsive element (IRE)-binding protein involved
in the control of iron metabolism or as the cytoplasmic isoform of
aconitase. Aconitases are iron-sulfur proteins that require a 4Fe-4S
cluster for their enzymatic activity, in which they catalyze conversion
of citrate to isocitrate (EC 4.2.1.3) (Eisenstein, 2000).
CLONING
Rouault et al. (1990) used RNA affinity chromatography and 2-dimensional
gel electrophoresis to isolate IREBP for protein sequencing. They used
an oligonucleotide probe derived from the peptide sequence to isolate a
cDNA encoding a protein of 87 kD. The corresponding mRNA of about 3.6 kb
was found in a variety of cell types.
GENE FUNCTION
Aconitase-1 functions as a cytoplasmic IRE-binding protein (IREBP). IREs
are translational regulatory sequences in the 5-prime UTR of ferritin
(see 134790) mRNA and in the 3-prime UTR of transferrin receptor mRNA
(190010). The cytoplasmic IREBP interacts with the IREs of these mRNAs.
The iron status of the cell determines the ability of IREBP to bind to
an IRE through reversible oxidation-reduction of sulfhydryl groups that
are critical for the high-affinity RNA-protein interaction. Thus, IREBP
plays a central role in cellular iron homeostasis by regulating ferritin
mRNA translation and TFRC mRNA stability (Hentze et al., 1989).
Eisenstein (2000) reviewed of the role of the iron regulatory proteins,
IRP1 and IRP2 (147582), and the molecular control of mammalian iron
metabolism.
Meyron-Holtz et al. (2004) found that IRP2-null cells misregulated iron
metabolism when cultured in 3 to 6% oxygen, which is comparable to
physiologic tissue concentrations, but not in 21% oxygen, a
concentration that activated IRP1 and allowed it to substitute for IRP2.
Thus, IRP2 dominates regulation of mammalian iron homeostasis because it
alone registers iron concentrations and modulates its RNA-binding
activity at physiologic oxygen tensions.
Condo et al. (2010) demonstrated that the extramitochondrial form of
frataxin (FXN; 606829) directly interacted with IRP1 through the
'iron-sulfur switch' mechanism. Cytosolic aconitase defect and
consequent IRP1 activation occurring in Friedreich ataxia cells were
reversed by the action of extramitochondrial frataxin.
BIOCHEMICAL FEATURES
- Crystal Structure
IRP1 binds IREs in mRNAs, to repress translation or degradation, or
binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme.
Walden et al. (2006) determined the crystal structure of IRP1 bound to
ferritin H (134770) IRE to 2.8-angstrom resolution. The IRP1:ferritin H
IRE complex showed an open protein conformation compared with that of
cytosolic aconitase. The extended, L-shaped IRP1 molecule embraced the
IRE stem loop through interactions at 2 sites separated by about 30
angstroms, each involving about a dozen protein:RNA bonds. Walden et al.
(2006) concluded that extensive conformational changes related to
binding the IRE or an iron-sulfur cluster explain the alternate
functions of IRP1 as an mRNA regulator or enzyme.
MAPPING
In studies of man-Chinese hamster somatic cell hybrids, Westerveld et
al. (1975) showed that human gal-1-p uridyl transferase (GALT; 606999)
and aconitase are syntenic.
Povey et al. (1976) assigned the ACO1 gene to chromosome 9. ACO1 and
GALT are on chromosome 9p in man and on chromosome 4 in the mouse
(Nadeau and Eicher, 1982). The location in the mouse was predicted from
the human linkage. The smallest region of overlap for ACO1 was estimated
to be 9p22-p13 (Robson and Meera Khan, 1982).
Because of the possibility that idiopathic hemochromatosis, which is the
result of a mutant gene that maps to 6p21, is due to mutation in IREBP,
Hentze et al. (1989) attempted to map the IREBP gene. Since the gene had
not been cloned, and since they did not have specific antibodies for the
protein, they mapped the gene in human/rodent hybrid cells by taking
advantage of the different mobilities of the human and rodent IRE/IREBP
complexes on nondenaturing polyacrylamide gels. Using a panel of 34
different hybrid cell lines, they assigned the IREBP gene to human
chromosome 9. Southern hybridization analysis of rodent-human somatic
hybrid cell lines by Rouault et al. (1990) corroborated the assignment
of IREBP to chromosome 9. A high frequency RFLP was also identified.
By interspecific backcross linkage analysis, Pilz et al. (1995) mapped
the Irebp gene to mouse chromosome 4.
MOLECULAR GENETICS
Schmitt and Ritter (1974) found electrophoretic variants of the soluble
form of aconitate hydratase in human placenta. No mitochondrial variants
were found.
Slaughter et al. (1975) reported an electrophoretic survey that
demonstrated 7 alleles at the ACONS locus. Among the populations
studied, Nigerians showed polymorphism for ACONS.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
EVOLUTION
Aconitase-1 and aconitase-2 (ACO2; 100850) are isozymes present in the
cytosol and mitochondria, respectively. Other pairs of cytosolic and
mitochondrial isozymes are ALDH1 (100640) and ALDH2 (100650), GOT1
(138180) and GOT2 (138150), IDH1 (147700) and IDH2 (147650), MDH1
(154200) and MDH2 (154100), SOD1 (147450) and SOD2 (147460), and TK1
(188300) and TK2 (188250). In all these cases, the 2 isozymes of
different subcellular localization, although similar in structure and
function, are encoded by genes on different chromosomes, i.e., are
nonsyntenic. The presumption is that in each case both originated from a
common ancestral gene in a primordial genome, but that whereas the
cytosolic isozyme is encoded by a gene that is a direct descendant from
a nuclear progenitor gene, the mitochondrial isozyme, although now
encoded by a nuclear gene, is descended from a gene in the
bacterium-like progenitor of the mitochondrion. When this primitive
organism took up intracellular existence, most of its genes were
transferred to the nuclear genome and since they inserted more or less
at random into the nuclear genome, it was to be expected that the
cytosolic and mitochondrial forms of the enzyme would end up being
encoded by genes on different chromosomes. That mitochondrial DNA can be
inserted into the nuclear genome is indicated by work such as that of
Shay and Werbin (1992) who characterized in detail 2 instances of
mitochondrial DNA fragments that had been inserted into the nucleus of
HeLa cells. In one of these cases, the mitochondrial sequence encoding
cytochrome c oxidase subunit III was contiguous with and 5-prime of
exons 2 and 3 of the MYC oncogene (190080) and the chimeric gene was
transcribed. Shay and Werbin (1992) discussed possible mechanisms for
the transfer of mitochondrial DNA into the nucleus.
*FIELD* SA
Azevedo et al. (1979); Mohandas et al. (1979); Robson et al. (1977);
Shows and Brown (1977); Teng et al. (1978)
*FIELD* RF
1. Azevedo, E. S.; Da Silva, M. C. B. O.; Lima, A. M. V.; Fonseca,
E. F.; Conseicao, M. M.: Human aconitase polymorphism in three samples
from northeastern Brazil. Ann. Hum. Genet. 43: 7-10, 1979.
2. Condo, I.; Malisan, F.; Guccini, I.; Serio, D.; Rufini, A.; Testi,
R.: Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial
frataxin. Hum. Molec. Genet. 19: 1221-1229, 2010.
3. Eisenstein, R. S.: Iron regulatory proteins and the molecular
control of mammalian iron metabolism. Annu. Rev. Nutr. 20: 627-662,
2000.
4. Hentze, M. W.; Seuanez, H. N.; O'Brien, S. J.; Harford, J. B.;
Klausner, R. D.: Chromosomal localization of nucleic acid-binding
proteins by affinity mapping: assignment of the IRE-binding protein
gene to human chromosome 9. Nucleic Acids Res. 17: 6103-6108, 1989.
5. Meyron-Holtz, E. G.; Ghosh, M. C.; Rouault, T. A.: Mammalian tissue
oxygen levels modulate iron-regulatory protein activities in vivo. Science 306:
2087-2090, 2004.
6. Mohandas, T.; Sparkes, R. S.; Sparkes, M. C.; Shulkin, J. D.; Toomey,
K. E.; Funderburk, S. J.: Regional localization of human gene loci
on chromosome 9: studies of somatic cell hybrids containing human
translocations. Am. J. Hum. Genet. 31: 586-600, 1979.
7. Nadeau, J. H.; Eicher, E. M.: Conserved linkage of soluble aconitase
and galactose-1-phosphate uridyl transferase in mouse and man: assignment
of these genes to mouse chromosome 4. Cytogenet. Cell Genet. 34:
271-281, 1982.
8. Pilz, A.; Woodward, K.; Povey, S.; Abbott, C.: Comparative mapping
of 50 human chromosome 9 loci in the laboratory mouse. Genomics 25:
139-149, 1995.
9. Povey, S.; Slaughter, C. A.; Wilson, D. E.; Gormley, I. P.; Buckton,
K. E.; Perry, P.; Bobrow, M.: Evidence for the assignment of the
loci AK 1, AK 3 and ACON to chromosome 9 in man. Ann. Hum. Genet. 39:
413-422, 1976.
10. Robson, E. B.; Cook, P. J. L.; Buckton, K. E.: Family studies
with the chromosome 9 markers ABO, AK-1, ACON-S and 9qh. Ann. Hum.
Genet. 41: 53-60, 1977.
11. Robson, E. B.; Meera Khan, P.: Report of the committee on the
genetic constitution of chromosomes 7, 8, and 9. Cytogenet. Cell
Genet. 32: 144-152, 1982.
12. 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.: Cloning of the cDNA encoding an RNA regulatory protein: the human
iron-responsive element-binding protein. Proc. Nat. Acad. Sci. 87:
7958-7962, 1990.
13. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
14. Schmitt, J.; Ritter, H.: Genetic variation of aconitate hydratase
in man. Humangenetik 22: 263-264, 1974.
15. Shay, J. W.; Werbin, H.: New evidence for the insertion of mitochondrial
DNA into the human genome: significance for cancer and aging. Mutat.
Res. 275: 227-235, 1992.
16. Shows, T. B.; Brown, J. A.: Mapping AK-1, ACON-S, and AK-3 to
chromosome 9 in man employing an X-9 translocation and somatic cell
hybrids. Cytogenet. Cell Genet. 19: 26-37, 1977.
17. Slaughter, C. A.; Hopkinson, D. A.; Harris, H.: Aconitase polymorphism
in man. Ann. Hum. Genet. 39: 193-202, 1975.
18. Teng, Y. S.; Tan, S. G.; Lopez, C. G.: Red cell glyoxalase I
and placental soluble aconitase polymorphisms in the three major ethnic
groups of Malaysia. Jpn. J. Hum. Genet. 23: 211-215, 1978.
19. Walden, W. E.; Selezneva, A. I.; Dupuy, J.; Volbeda, A.; Fontecilla-Camps,
J. C.; Theil, E. C.; Volz, K.: Structure of dual function iron regulatory
protein 1 complexed with ferritin IRE-RNA. Science 314: 1903-1908,
2006.
20. Westerveld, A.; van Henegouwen, B. H. M. A.; Van Someren, H.:
Evidence for synteny between the human loci for galactose-1-phosphate
uridyl transferase and aconitase in man-Chinese hamster somatic cell
hybrids. Cytogenet. Cell Genet. 14: 453-454, 1975.
*FIELD* CN
George E. Tiller - updated: 11/14/2011
Matthew B. Gross - updated: 3/20/2008
Ada Hamosh - updated: 2/6/2007
Ada Hamosh - updated: 1/27/2005
Victor A. McKusick - updated: 9/28/2001
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/15/2011
terry: 11/14/2011
carol: 5/3/2010
mgross: 3/20/2008
alopez: 2/8/2007
terry: 2/6/2007
wwang: 2/3/2005
terry: 1/27/2005
carol: 6/7/2002
carol: 10/3/2001
mcapotos: 9/28/2001
carol: 7/12/2000
mimadm: 2/11/1994
carol: 2/17/1993
carol: 2/2/1993
carol: 8/25/1992
supermim: 3/16/1992
carol: 12/6/1990
*RECORD*
*FIELD* NO
100880
*FIELD* TI
*100880 ACONITASE 1, SOLUBLE; ACO1
;;ACONITATE HYDRATASE, SOLUBLE;;
ACONITASE, SOLUBLE; ACONS;;
read moreIRON-RESPONSIVE ELEMENT-BINDING PROTEIN 1; IREB1;;
IRE-BINDING PROTEIN 1; IREBP1; IREBP;;
IRON REGULATORY PROTEIN 1; IRP1
*FIELD* TX
DESCRIPTION
Soluble aconitase is a bifunctional protein with mutually exclusive
functions as an iron responsive element (IRE)-binding protein involved
in the control of iron metabolism or as the cytoplasmic isoform of
aconitase. Aconitases are iron-sulfur proteins that require a 4Fe-4S
cluster for their enzymatic activity, in which they catalyze conversion
of citrate to isocitrate (EC 4.2.1.3) (Eisenstein, 2000).
CLONING
Rouault et al. (1990) used RNA affinity chromatography and 2-dimensional
gel electrophoresis to isolate IREBP for protein sequencing. They used
an oligonucleotide probe derived from the peptide sequence to isolate a
cDNA encoding a protein of 87 kD. The corresponding mRNA of about 3.6 kb
was found in a variety of cell types.
GENE FUNCTION
Aconitase-1 functions as a cytoplasmic IRE-binding protein (IREBP). IREs
are translational regulatory sequences in the 5-prime UTR of ferritin
(see 134790) mRNA and in the 3-prime UTR of transferrin receptor mRNA
(190010). The cytoplasmic IREBP interacts with the IREs of these mRNAs.
The iron status of the cell determines the ability of IREBP to bind to
an IRE through reversible oxidation-reduction of sulfhydryl groups that
are critical for the high-affinity RNA-protein interaction. Thus, IREBP
plays a central role in cellular iron homeostasis by regulating ferritin
mRNA translation and TFRC mRNA stability (Hentze et al., 1989).
Eisenstein (2000) reviewed of the role of the iron regulatory proteins,
IRP1 and IRP2 (147582), and the molecular control of mammalian iron
metabolism.
Meyron-Holtz et al. (2004) found that IRP2-null cells misregulated iron
metabolism when cultured in 3 to 6% oxygen, which is comparable to
physiologic tissue concentrations, but not in 21% oxygen, a
concentration that activated IRP1 and allowed it to substitute for IRP2.
Thus, IRP2 dominates regulation of mammalian iron homeostasis because it
alone registers iron concentrations and modulates its RNA-binding
activity at physiologic oxygen tensions.
Condo et al. (2010) demonstrated that the extramitochondrial form of
frataxin (FXN; 606829) directly interacted with IRP1 through the
'iron-sulfur switch' mechanism. Cytosolic aconitase defect and
consequent IRP1 activation occurring in Friedreich ataxia cells were
reversed by the action of extramitochondrial frataxin.
BIOCHEMICAL FEATURES
- Crystal Structure
IRP1 binds IREs in mRNAs, to repress translation or degradation, or
binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme.
Walden et al. (2006) determined the crystal structure of IRP1 bound to
ferritin H (134770) IRE to 2.8-angstrom resolution. The IRP1:ferritin H
IRE complex showed an open protein conformation compared with that of
cytosolic aconitase. The extended, L-shaped IRP1 molecule embraced the
IRE stem loop through interactions at 2 sites separated by about 30
angstroms, each involving about a dozen protein:RNA bonds. Walden et al.
(2006) concluded that extensive conformational changes related to
binding the IRE or an iron-sulfur cluster explain the alternate
functions of IRP1 as an mRNA regulator or enzyme.
MAPPING
In studies of man-Chinese hamster somatic cell hybrids, Westerveld et
al. (1975) showed that human gal-1-p uridyl transferase (GALT; 606999)
and aconitase are syntenic.
Povey et al. (1976) assigned the ACO1 gene to chromosome 9. ACO1 and
GALT are on chromosome 9p in man and on chromosome 4 in the mouse
(Nadeau and Eicher, 1982). The location in the mouse was predicted from
the human linkage. The smallest region of overlap for ACO1 was estimated
to be 9p22-p13 (Robson and Meera Khan, 1982).
Because of the possibility that idiopathic hemochromatosis, which is the
result of a mutant gene that maps to 6p21, is due to mutation in IREBP,
Hentze et al. (1989) attempted to map the IREBP gene. Since the gene had
not been cloned, and since they did not have specific antibodies for the
protein, they mapped the gene in human/rodent hybrid cells by taking
advantage of the different mobilities of the human and rodent IRE/IREBP
complexes on nondenaturing polyacrylamide gels. Using a panel of 34
different hybrid cell lines, they assigned the IREBP gene to human
chromosome 9. Southern hybridization analysis of rodent-human somatic
hybrid cell lines by Rouault et al. (1990) corroborated the assignment
of IREBP to chromosome 9. A high frequency RFLP was also identified.
By interspecific backcross linkage analysis, Pilz et al. (1995) mapped
the Irebp gene to mouse chromosome 4.
MOLECULAR GENETICS
Schmitt and Ritter (1974) found electrophoretic variants of the soluble
form of aconitate hydratase in human placenta. No mitochondrial variants
were found.
Slaughter et al. (1975) reported an electrophoretic survey that
demonstrated 7 alleles at the ACONS locus. Among the populations
studied, Nigerians showed polymorphism for ACONS.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
EVOLUTION
Aconitase-1 and aconitase-2 (ACO2; 100850) are isozymes present in the
cytosol and mitochondria, respectively. Other pairs of cytosolic and
mitochondrial isozymes are ALDH1 (100640) and ALDH2 (100650), GOT1
(138180) and GOT2 (138150), IDH1 (147700) and IDH2 (147650), MDH1
(154200) and MDH2 (154100), SOD1 (147450) and SOD2 (147460), and TK1
(188300) and TK2 (188250). In all these cases, the 2 isozymes of
different subcellular localization, although similar in structure and
function, are encoded by genes on different chromosomes, i.e., are
nonsyntenic. The presumption is that in each case both originated from a
common ancestral gene in a primordial genome, but that whereas the
cytosolic isozyme is encoded by a gene that is a direct descendant from
a nuclear progenitor gene, the mitochondrial isozyme, although now
encoded by a nuclear gene, is descended from a gene in the
bacterium-like progenitor of the mitochondrion. When this primitive
organism took up intracellular existence, most of its genes were
transferred to the nuclear genome and since they inserted more or less
at random into the nuclear genome, it was to be expected that the
cytosolic and mitochondrial forms of the enzyme would end up being
encoded by genes on different chromosomes. That mitochondrial DNA can be
inserted into the nuclear genome is indicated by work such as that of
Shay and Werbin (1992) who characterized in detail 2 instances of
mitochondrial DNA fragments that had been inserted into the nucleus of
HeLa cells. In one of these cases, the mitochondrial sequence encoding
cytochrome c oxidase subunit III was contiguous with and 5-prime of
exons 2 and 3 of the MYC oncogene (190080) and the chimeric gene was
transcribed. Shay and Werbin (1992) discussed possible mechanisms for
the transfer of mitochondrial DNA into the nucleus.
*FIELD* SA
Azevedo et al. (1979); Mohandas et al. (1979); Robson et al. (1977);
Shows and Brown (1977); Teng et al. (1978)
*FIELD* RF
1. Azevedo, E. S.; Da Silva, M. C. B. O.; Lima, A. M. V.; Fonseca,
E. F.; Conseicao, M. M.: Human aconitase polymorphism in three samples
from northeastern Brazil. Ann. Hum. Genet. 43: 7-10, 1979.
2. Condo, I.; Malisan, F.; Guccini, I.; Serio, D.; Rufini, A.; Testi,
R.: Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial
frataxin. Hum. Molec. Genet. 19: 1221-1229, 2010.
3. Eisenstein, R. S.: Iron regulatory proteins and the molecular
control of mammalian iron metabolism. Annu. Rev. Nutr. 20: 627-662,
2000.
4. Hentze, M. W.; Seuanez, H. N.; O'Brien, S. J.; Harford, J. B.;
Klausner, R. D.: Chromosomal localization of nucleic acid-binding
proteins by affinity mapping: assignment of the IRE-binding protein
gene to human chromosome 9. Nucleic Acids Res. 17: 6103-6108, 1989.
5. Meyron-Holtz, E. G.; Ghosh, M. C.; Rouault, T. A.: Mammalian tissue
oxygen levels modulate iron-regulatory protein activities in vivo. Science 306:
2087-2090, 2004.
6. Mohandas, T.; Sparkes, R. S.; Sparkes, M. C.; Shulkin, J. D.; Toomey,
K. E.; Funderburk, S. J.: Regional localization of human gene loci
on chromosome 9: studies of somatic cell hybrids containing human
translocations. Am. J. Hum. Genet. 31: 586-600, 1979.
7. Nadeau, J. H.; Eicher, E. M.: Conserved linkage of soluble aconitase
and galactose-1-phosphate uridyl transferase in mouse and man: assignment
of these genes to mouse chromosome 4. Cytogenet. Cell Genet. 34:
271-281, 1982.
8. Pilz, A.; Woodward, K.; Povey, S.; Abbott, C.: Comparative mapping
of 50 human chromosome 9 loci in the laboratory mouse. Genomics 25:
139-149, 1995.
9. Povey, S.; Slaughter, C. A.; Wilson, D. E.; Gormley, I. P.; Buckton,
K. E.; Perry, P.; Bobrow, M.: Evidence for the assignment of the
loci AK 1, AK 3 and ACON to chromosome 9 in man. Ann. Hum. Genet. 39:
413-422, 1976.
10. Robson, E. B.; Cook, P. J. L.; Buckton, K. E.: Family studies
with the chromosome 9 markers ABO, AK-1, ACON-S and 9qh. Ann. Hum.
Genet. 41: 53-60, 1977.
11. Robson, E. B.; Meera Khan, P.: Report of the committee on the
genetic constitution of chromosomes 7, 8, and 9. Cytogenet. Cell
Genet. 32: 144-152, 1982.
12. 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.: Cloning of the cDNA encoding an RNA regulatory protein: the human
iron-responsive element-binding protein. Proc. Nat. Acad. Sci. 87:
7958-7962, 1990.
13. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
14. Schmitt, J.; Ritter, H.: Genetic variation of aconitate hydratase
in man. Humangenetik 22: 263-264, 1974.
15. Shay, J. W.; Werbin, H.: New evidence for the insertion of mitochondrial
DNA into the human genome: significance for cancer and aging. Mutat.
Res. 275: 227-235, 1992.
16. Shows, T. B.; Brown, J. A.: Mapping AK-1, ACON-S, and AK-3 to
chromosome 9 in man employing an X-9 translocation and somatic cell
hybrids. Cytogenet. Cell Genet. 19: 26-37, 1977.
17. Slaughter, C. A.; Hopkinson, D. A.; Harris, H.: Aconitase polymorphism
in man. Ann. Hum. Genet. 39: 193-202, 1975.
18. Teng, Y. S.; Tan, S. G.; Lopez, C. G.: Red cell glyoxalase I
and placental soluble aconitase polymorphisms in the three major ethnic
groups of Malaysia. Jpn. J. Hum. Genet. 23: 211-215, 1978.
19. Walden, W. E.; Selezneva, A. I.; Dupuy, J.; Volbeda, A.; Fontecilla-Camps,
J. C.; Theil, E. C.; Volz, K.: Structure of dual function iron regulatory
protein 1 complexed with ferritin IRE-RNA. Science 314: 1903-1908,
2006.
20. Westerveld, A.; van Henegouwen, B. H. M. A.; Van Someren, H.:
Evidence for synteny between the human loci for galactose-1-phosphate
uridyl transferase and aconitase in man-Chinese hamster somatic cell
hybrids. Cytogenet. Cell Genet. 14: 453-454, 1975.
*FIELD* CN
George E. Tiller - updated: 11/14/2011
Matthew B. Gross - updated: 3/20/2008
Ada Hamosh - updated: 2/6/2007
Ada Hamosh - updated: 1/27/2005
Victor A. McKusick - updated: 9/28/2001
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/15/2011
terry: 11/14/2011
carol: 5/3/2010
mgross: 3/20/2008
alopez: 2/8/2007
terry: 2/6/2007
wwang: 2/3/2005
terry: 1/27/2005
carol: 6/7/2002
carol: 10/3/2001
mcapotos: 9/28/2001
carol: 7/12/2000
mimadm: 2/11/1994
carol: 2/17/1993
carol: 2/2/1993
carol: 8/25/1992
supermim: 3/16/1992
carol: 12/6/1990