ID   ACOHC_RAT               Reviewed;         889 AA.
AC   Q63270;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 162.
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 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, Irebp;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=1527027; DOI=10.1016/s0021-9258(19)37060-7;
RA   Yu Y., Radisky E.S., Leibold E.A.;
RT   "The iron-responsive element binding protein. Purification, cloning, and
RT   regulation in rat liver.";
RL   J. Biol. Chem. 267:19005-19010(1992).
RN   [2]
RP   PROTEIN SEQUENCE OF 114-134 AND 277-293, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA   Lubec G., Diao W.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [3]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16144863; DOI=10.1242/jcs.02570;
RA   Patton S.M., Pinero D.J., Surguladze N., Beard J., Connor J.R.;
RT   "Subcellular localization of iron regulatory proteins to Golgi and ER
RT   membranes.";
RL   J. Cell Sci. 118:4365-4373(2005).
CC   -!- FUNCTION: Bifunctional iron sensor that switches between 2 activities
CC       depending on iron availability (By similarity). Iron deprivation,
CC       promotes its mRNA binding activity through which it regulates the
CC       expression of genes involved in iron uptake, sequestration and
CC       utilization (PubMed:16144863). Binds to iron-responsive elements (IRES)
CC       in the untranslated region of target mRNAs preventing for instance the
CC       translation of ferritin and aminolevulinic acid synthase and
CC       stabilizing the transferrin receptor mRNA (PubMed:16144863).
CC       {ECO:0000250|UniProtKB:P21399, ECO:0000269|PubMed:16144863}.
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:16144863}.
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; L23874; AAA41449.1; -; mRNA.
DR   PIR; A44154; A44154.
DR   RefSeq; NP_059017.1; NM_017321.1.
DR   AlphaFoldDB; Q63270; -.
DR   SMR; Q63270; -.
DR   BioGRID; 248407; 1.
DR   STRING; 10116.ENSRNOP00000008337; -.
DR   iPTMnet; Q63270; -.
DR   PhosphoSitePlus; Q63270; -.
DR   SwissPalm; Q63270; -.
DR   jPOST; Q63270; -.
DR   PaxDb; 10116-ENSRNOP00000008337; -.
DR   GeneID; 50655; -.
DR   KEGG; rno:50655; -.
DR   UCSC; RGD:2019; rat.
DR   AGR; RGD:2019; -.
DR   CTD; 48; -.
DR   RGD; 2019; Aco1.
DR   eggNOG; KOG0452; Eukaryota.
DR   InParanoid; Q63270; -.
DR   OrthoDB; 176941at2759; -.
DR   BRENDA; 4.2.1.3; 5301.
DR   Reactome; R-RNO-917937; Iron uptake and transport.
DR   SABIO-RK; Q63270; -.
DR   PRO; PR:Q63270; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; ISO:RGD.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISS:UniProtKB.
DR   GO; GO:0003994; F:aconitate hydratase activity; IDA:RGD.
DR   GO; GO:0030350; F:iron-responsive element binding; IDA:RGD.
DR   GO; GO:0051536; F:iron-sulfur cluster binding; IDA:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0048027; F:mRNA 5'-UTR binding; IDA:RGD.
DR   GO; GO:0003723; F:RNA binding; IDA:RGD.
DR   GO; GO:0006101; P:citrate metabolic process; ISS:UniProtKB.
DR   GO; GO:0050892; P:intestinal absorption; ISO:RGD.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; IDA:RGD.
DR   GO; GO:0001889; P:liver development; IEP:RGD.
DR   GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR   GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR   GO; GO:0006417; P:regulation of translation; ISO:RGD.
DR   GO; GO:0010040; P:response to iron(II) ion; ISS:UniProtKB.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR   CDD; cd01586; AcnA_IRP; 1.
DR   CDD; cd01580; AcnA_IRP_Swivel; 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   PANTHER; PTHR11670; ACONITASE/IRON-RESPONSIVE ELEMENT FAMILY MEMBER; 1.
DR   PANTHER; PTHR11670:SF32; CYTOPLASMIC ACONITATE HYDRATASE; 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   1: Evidence at protein level;
KW   4Fe-4S; Cytoplasm; Direct protein sequencing; Iron; Iron-sulfur; Lyase;
KW   Metal-binding; Reference proteome; RNA-binding; Tricarboxylic acid cycle.
FT   CHAIN           1..889
FT                   /note="Cytoplasmic aconitate hydratase"
FT                   /id="PRO_0000076683"
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"
FT   CONFLICT        131
FT                   /note="H -> D (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   889 AA;  98128 MW;  610486302B4362CD CRC64;
     MKNPFAHLAE PLDPAQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAVRNC DEFLVKKNDI
     ENILNWSIMQ HKSIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGN PEKINPVCPA
     DLVIDHSIQV HFNRRADSLQ KNQDLEFERN RERFEFLKWG SQAFCNMRII PPGSGIIHQV
     NLEYLARVVF DQDGCYYPDS LVGTDSHTTM IDGLGVLGWG VGGIEAEAVM LGQPISMVLP
     QVIGYKLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC
     PEYGATAAFF PVDDVSIAYL VQTGREEDKV KHIKRYLQAV GMFRDFSDSS QDPDFTQVVE
     LDLKTVVPCC SGPKRPQDKV AVSEIEKDFE SCLGAKQGFK GFQVAPDHHN DHKTFIYNDS
     EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVEAG LNVKPYVKTS LSPGSGVVTY
     YLRESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG
     RVHPNTRANY LASPPLVIAY AIAGTVRIDF EKEPLGVNAQ GQQVFLKDIW PTRDEIQEVE
     RKYVIPGMFK EVYQKIETVN KSWNALAAPS EKLYAWNPKS TYIKSPPFFE SLTLDLQPPK
     SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPRDFNSYG SRRGNDAIMA
     RGTFANIRLL NKFLNKQAPQ TVHLPSGETL DVFDAAERYQ QAGLPLIVLA GKEYGSGSSR
     DWAAKGPFLL GIKAVLAESY ERTHCSNLVG MGVIPLEYLP GETADSLGLT GRERYTIHIP
     EHLKPRMKVQ IKLDTGKTFQ AVMRFDTDVE LTYFHNGGIL NYMIRKMAQ
//