ACOHC_RAT
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 03-AUG-2022, entry version 156.
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}.
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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 jPOST; Q63270; -.
DR PaxDb; Q63270; -.
DR PRIDE; Q63270; -.
DR GeneID; 50655; -.
DR KEGG; rno:50655; -.
DR UCSC; RGD:2019; rat.
DR CTD; 48; -.
DR RGD; 2019; Aco1.
DR eggNOG; KOG0452; Eukaryota.
DR InParanoid; Q63270; -.
DR OrthoDB; 190960at2759; -.
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; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
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:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
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:0006879; P:cellular iron ion homeostasis; IDA:RGD.
DR GO; GO:0006101; P:citrate metabolic process; ISS:UniProtKB.
DR GO; GO:0050892; P:intestinal absorption; ISO: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; cd01580; AcnA_IRP_Swivel; 1.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 2.
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 InterPro; IPR029784; IRE-BP1.
DR PANTHER; PTHR11670; PTHR11670; 1.
DR PANTHER; PTHR11670:SF32; PTHR11670:SF32; 1.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
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 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
