ID ACOHC_BOVIN Reviewed; 889 AA. AC Q0VCU1; DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 1. DT 02-SEP-2026, entry version 110. DE RecName: Full=Cytoplasmic aconitate hydratase {ECO:0000305}; DE Short=Aconitase; DE EC=4.2.1.3 {ECO:0000250|UniProtKB:P21399}; DE AltName: Full=Citrate hydro-lyase; DE AltName: Full=Iron-responsive element-binding protein 1; DE Short=IRE-BP 1; GN Name=ACO1; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal pons; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1281544; DOI=10.1073/pnas.89.24.11735; RA Haile D.J., Rouault T.A., Harford J.B., Kennedy M.C., Blondin G.A., RA Beinert H., Klausner R.D.; RT "Cellular regulation of the iron-responsive element binding protein: RT disassembly of the cubane iron-sulfur cluster results in high-affinity RNA RT binding."; RL Proc. Natl. Acad. Sci. U.S.A. 89:11735-11739(1992). CC -!- FUNCTION: Bifunctional iron sensor that switches between 2 activities CC depending on iron availability. Iron deprivation, promotes its mRNA CC binding activity through which it regulates the expression of genes CC involved in iron uptake, sequestration and utilization. Binds to iron- CC responsive elements (IRES) in the untranslated region of target mRNAs CC preventing for instance the translation of ferritin and aminolevulinic CC acid synthase and stabilizing the transferrin receptor mRNA. CC {ECO:0000269|PubMed:1281544}. CC -!- FUNCTION: Conversely, when cellular iron levels are high, binds a 4Fe- CC 4S cluster which precludes RNA binding activity and promotes the CC aconitase activity, the isomerization of citrate to isocitrate via cis- CC aconitate. {ECO:0000250|UniProtKB:P21399}. CC -!- CATALYTIC ACTIVITY: CC Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336, CC ChEBI:CHEBI:15562, ChEBI:CHEBI:16947; EC=4.2.1.3; CC Evidence={ECO:0000250|UniProtKB:P21399}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000250|UniProtKB:P21399}; CC Note=Binds 1 [4Fe-4S] cluster per subunit. CC {ECO:0000250|UniProtKB:P21399}; CC -!- SUBUNIT: Interacts (when associated with the 4Fe-4S) with FBXL5. CC Interacts with frataxin(81-210). {ECO:0000250|UniProtKB:P21399}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:1281544}. CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC120006; AAI20007.1; -; mRNA. DR RefSeq; NP_001069059.1; NM_001075591.1. DR AlphaFoldDB; Q0VCU1; -. DR SMR; Q0VCU1; -. DR FunCoup; Q0VCU1; 1383. DR STRING; 9913.ENSBTAP00000070636; -. DR MoonProt; Q0VCU1; -. DR PaxDb; 9913-ENSBTAP00000070636; -. DR PeptideAtlas; Q0VCU1; -. DR GeneID; 512995; -. DR KEGG; bta:512995; -. DR CTD; 48; -. DR eggNOG; KOG0452; Eukaryota. DR InParanoid; Q0VCU1; -. DR OrthoDB; 2279155at2759; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005737; C:cytoplasm; IDA:CAFA. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; IDA:CAFA. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:CAFA. DR GO; GO:0003994; F:aconitate hydratase activity; IDA:CAFA. DR GO; GO:0008198; F:ferrous iron binding; IDA:CAFA. DR GO; GO:0030350; F:iron-responsive element binding; IDA:CAFA. DR GO; GO:0006101; P:citrate metabolic process; IDA:CAFA. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IBA:GO_Central. DR GO; GO:0010040; P:response to iron(II) ion; ISS:UniProtKB. DR CDD; cd01586; AcnA_IRP; 1. DR CDD; cd01580; AcnA_IRP_Swivel; 1. DR FunFam; 3.30.499.10:FF:000002; Aconitate hydratase; 1. DR FunFam; 3.30.499.10:FF:000005; cytoplasmic aconitate hydratase; 1. DR FunFam; 3.20.19.10:FF:000005; Iron-responsive element-binding protein 2; 1. DR Gene3D; 6.10.190.10; -; 1. DR Gene3D; 3.30.499.10; Aconitase, domain 3; 2. DR Gene3D; 3.20.19.10; Aconitase, domain 4; 1. DR InterPro; IPR044137; AcnA_IRP_Swivel. DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3. DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba. DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl. DR InterPro; IPR006249; Aconitase/IRP2. DR InterPro; IPR018136; Aconitase_4Fe-4S_BS. DR InterPro; IPR036008; Aconitase_4Fe-4S_dom. DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl. DR NCBIfam; TIGR01341; aconitase_1; 1. DR NCBIfam; NF006757; PRK09277.1; 1. DR NCBIfam; NF009520; PRK12881.1; 1. DR PANTHER; PTHR11670; ACONITASE/IRON-RESPONSIVE ELEMENT FAMILY MEMBER; 1. DR Pfam; PF00330; Aconitase; 1. DR Pfam; PF00694; Aconitase_C; 1. DR PRINTS; PR00415; ACONITASE. DR SUPFAM; SSF53732; Aconitase iron-sulfur domain; 1. DR SUPFAM; SSF52016; LeuD/IlvD-like; 1. DR PROSITE; PS00450; ACONITASE_1; 1. DR PROSITE; PS01244; ACONITASE_2; 1. PE 2: Evidence at transcript level; KW 4Fe-4S; Cytoplasm; Iron; Iron-sulfur; Lyase; Metal-binding; KW Reference proteome; RNA-binding; Tricarboxylic acid cycle. FT CHAIN 1..889 FT /note="Cytoplasmic aconitate hydratase" FT /id="PRO_0000285207" FT BINDING 86 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 205..207 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 437 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 503 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 506 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 536 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 541 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 699 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 779..780 FT /ligand="substrate" FT /evidence="ECO:0000250" SQ SEQUENCE 889 AA; 98204 MW; 2BDD83B6294E6342 CRC64; MSNPFAHLVE PLDPAQPGKK FFNLNKLEDS RYGSLPFSIR VLLEAAIRNC DQFLVKKNDV ENILNWKVMQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGN PEKINPICPA DLVIDHSIQV DFNRRADSLK KNQDLEFERN KERFEFLKWG SQAFHNMRII PPGSGIIHQV NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGVLGWG VGGIEAEAVM LGQPISMVLP QVIGYRLVGN PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC PEYGATAAFF PVDEVSIKYL VQTGRDKEKV KHIKQYLQAV GMFRDFSDSS QDPDFAQVVE LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPDHHN DHKTFIYNNS KFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LSVKPYIKTS LSPGSGVVTY YLRESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEAVVEA IVQGDLVAVG VLSGNRNFEG RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE RQYVIPGMFK EVYQKIETVN ESWNALAAPS DKLYCWNPKS TYIKSPPFFE DLTLDLQPPK SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAIMA RGTFANIRLL NKFLNKQAPQ TIHLPSGEIL DVFDAAERYQ QAGLPLIVLA GKEYGSGSSR DWAAKGPFLL GIRAVLAESY ERIHRSNLVG MGVIPLEYLP GENADTLGLT GRERYTISIP ETLKPRMKVQ IKLDTGKTFQ AVMRFDTDVE LTYFHNGGIL NYMIRKMTK //