ACOHC_RABIT
ID ACOHC_RABIT Reviewed; 889 AA.
AC Q01059;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 136.
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=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=FRP, IREB1, IREBP;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=1527028; DOI=10.1016/s0021-9258(19)37061-9;
RA Patino M.M., Walden W.E.;
RT "Cloning of a functional cDNA for the rabbit ferritin mRNA repressor
RT protein. Demonstration of a tissue-specific pattern of expression.";
RL J. Biol. Chem. 267:19011-19016(1992).
RN [2]
RP PROTEIN SEQUENCE OF 133-146 AND 624-638.
RX PubMed=7518918; DOI=10.1093/nar/22.13.2627;
RA Swenson G.R., Walden W.E.;
RT "Localization of an RNA binding element of the iron responsive element
RT binding protein within a proteolytic fragment containing iron coordination
RT ligands.";
RL Nucleic Acids Res. 22:2627-2633(1994).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH TARGET MRNA,
RP RNA-BINDING, AND FUNCTION.
RX PubMed=17185597; DOI=10.1126/science.1133116;
RA Walden W.E., Selezneva A.I., Dupuy J., Volbeda A., Fontecilla-Camps J.C.,
RA Theil E.C., Volz K.;
RT "Structure of dual function iron regulatory protein 1 complexed with
RT ferritin IRE-RNA.";
RL Science 314:1903-1908(2006).
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:17185597). 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:17185597).
CC {ECO:0000250|UniProtKB:P21399, ECO:0000269|PubMed:17185597}.
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
CC {ECO:0000250|UniProtKB:P21399}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; M95815; AAA31255.1; -; mRNA.
DR PIR; A44153; A44153.
DR RefSeq; NP_001075784.1; NM_001082315.1.
DR PDB; 3SN2; X-ray; 2.99 A; A=2-889.
DR PDB; 3SNP; X-ray; 2.80 A; A/B=2-889.
DR PDBsum; 3SN2; -.
DR PDBsum; 3SNP; -.
DR AlphaFoldDB; Q01059; -.
DR SMR; Q01059; -.
DR STRING; 9986.ENSOCUP00000013749; -.
DR iPTMnet; Q01059; -.
DR PRIDE; Q01059; -.
DR GeneID; 100009154; -.
DR KEGG; ocu:100009154; -.
DR CTD; 48; -.
DR eggNOG; KOG0452; Eukaryota.
DR InParanoid; Q01059; -.
DR OrthoDB; 190960at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; ISS:UniProtKB.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0030350; F:iron-responsive element binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:InterPro.
DR GO; GO:0006101; P:citrate metabolic process; ISS:UniProtKB.
DR GO; GO:0010040; P:response to iron(II) ion; ISS:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
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 3D-structure; 4Fe-4S; Cytoplasm; Direct protein sequencing; Iron;
KW Iron-sulfur; Lyase; Metal-binding; Reference proteome; RNA-binding;
KW Tricarboxylic acid cycle.
FT CHAIN 1..889
FT /note="Cytoplasmic aconitate hydratase"
FT /id="PRO_0000076682"
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 HELIX 6..8
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 24..32
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 37..48
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 57..64
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 66..69
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 91..105
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 147..163
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 178..184
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 223..230
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 242..249
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 257..271
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 276..282
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 283..287
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 290..298
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 314..322
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 327..339
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 356..362
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 385..394
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 408..410
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 412..419
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 428..435
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 442..458
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 467..472
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 477..483
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 484..486
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 488..493
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 515..523
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 529..533
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 539..541
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 547..551
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 554..563
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 564..567
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 570..572
FT /evidence="ECO:0007829|PDB:3SN2"
FT STRAND 575..577
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 579..584
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 586..589
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 593..602
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 604..617
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 618..621
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 647..649
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 662..670
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 677..680
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 691..697
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 698..700
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 703..705
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 710..712
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 716..722
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 732..734
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 735..737
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 739..742
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 744..746
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 749..751
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 752..761
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 766..770
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 772..774
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 776..778
FT /evidence="ECO:0007829|PDB:3SNP"
FT TURN 781..784
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 785..789
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 792..798
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 802..810
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 814..817
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 824..827
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 835..837
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 848..853
FT /evidence="ECO:0007829|PDB:3SNP"
FT STRAND 858..863
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 868..876
FT /evidence="ECO:0007829|PDB:3SNP"
FT HELIX 879..887
FT /evidence="ECO:0007829|PDB:3SNP"
SQ SEQUENCE 889 AA; 98505 MW; 970C4DF4DD7A61D7 CRC64;
MSNPFAYLAE PLDPAQPGKK FFNLNKLDYS RYGRLPFSIR VLLEAAVRNC DKFLVKKEDI
ENILNWNVTQ HMNIEVPFKP ARVILQDFTG VPSVVDFAAM RDAVKKLGGD PEKINPICPV
DLVIDHSIQV DFNRRADSLQ KNQDLEFERN RERFEFLKWG SKAFRNMRII PPGSGIIHQV
NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGVLGWG VGGIEAEAVM LGQPISMVLP
QVIGYRLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGLGVAQLSI ADRATIANMC
PEYGATATFF PVDEVSIKYL VQTGRDESKV KQIRKYLQAV GMFRDYSDPS QDPDFTQVVE
LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPDHHN DHKTFIYNDS
EFTLSHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LNVKPYVKTS LSPGSGVVTY
YLRESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG
RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGTNAK GQQVFLRDIW PTREEIQAVE
RQYVIPGMFT EVYQKIETVN ASWNALAAPS DKLYLWNPKS TYIKSPPFFE NLTLDLQPPK
SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAIMA
RGTFANIRLL NRFLNKQAPQ TIHLPSGETL DVFDAAERYQ QEGHPLIVLA GKEYGSGSSR
DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GENADSLGLT GRERYTIIIP
ENLTPRMHVQ VKLDTGKTFQ AVIRFDTDVE LTYLHNGGIL NYMIRKMAK
