ACOHC_MOUSE
ID ACOHC_MOUSE Reviewed; 889 AA.
AC P28271; Q3TQ15; Q99K54;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 188.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=1956798; DOI=10.1093/nar/19.22.6333;
RA Philpott C.C., Rouault T.A., Klausner R.D.;
RT "Sequence and expression of the murine iron-responsive element binding
RT protein.";
RL Nucleic Acids Res. 19:6333-6333(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Binds to iron-responsive elements (IRES) in the
CC 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:1956798).
CC {ECO:0000250|UniProtKB:P21399, ECO:0000269|PubMed:1956798}.
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; X61147; CAA43455.1; -; mRNA.
DR EMBL; AK163985; BAE37570.1; -; mRNA.
DR EMBL; AL831793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05446.1; -; Genomic_DNA.
DR EMBL; BC005454; AAH05454.1; -; mRNA.
DR CCDS; CCDS18042.1; -.
DR PIR; S18720; S18720.
DR RefSeq; NP_031412.2; NM_007386.2.
DR AlphaFoldDB; P28271; -.
DR SMR; P28271; -.
DR BioGRID; 197924; 10.
DR IntAct; P28271; 1.
DR MINT; P28271; -.
DR STRING; 10090.ENSMUSP00000100038; -.
DR iPTMnet; P28271; -.
DR PhosphoSitePlus; P28271; -.
DR SwissPalm; P28271; -.
DR REPRODUCTION-2DPAGE; P28271; -.
DR SWISS-2DPAGE; P28271; -.
DR EPD; P28271; -.
DR jPOST; P28271; -.
DR MaxQB; P28271; -.
DR PaxDb; P28271; -.
DR PeptideAtlas; P28271; -.
DR PRIDE; P28271; -.
DR ProteomicsDB; 285594; -.
DR Antibodypedia; 10637; 600 antibodies from 39 providers.
DR DNASU; 11428; -.
DR Ensembl; ENSMUST00000102973; ENSMUSP00000100038; ENSMUSG00000028405.
DR GeneID; 11428; -.
DR KEGG; mmu:11428; -.
DR UCSC; uc008shd.1; mouse.
DR CTD; 48; -.
DR MGI; MGI:87879; Aco1.
DR VEuPathDB; HostDB:ENSMUSG00000028405; -.
DR eggNOG; KOG0452; Eukaryota.
DR GeneTree; ENSGT00940000157772; -.
DR HOGENOM; CLU_013476_2_1_1; -.
DR InParanoid; P28271; -.
DR OMA; NGGIMQY; -.
DR OrthoDB; 190960at2759; -.
DR PhylomeDB; P28271; -.
DR TreeFam; TF313476; -.
DR BRENDA; 4.2.1.3; 3474.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR BioGRID-ORCS; 11428; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Aco1; mouse.
DR PRO; PR:P28271; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P28271; protein.
DR Bgee; ENSMUSG00000028405; Expressed in aorta tunica adventitia and 252 other tissues.
DR Genevisible; P28271; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; ISO:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:MGI.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0030350; F:iron-responsive element binding; IDA:MGI.
DR GO; GO:0051536; F:iron-sulfur cluster binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:MGI.
DR GO; GO:0006101; P:citrate metabolic process; ISS:UniProtKB.
DR GO; GO:0050892; P:intestinal absorption; IGI:MGI.
DR GO; GO:0009791; P:post-embryonic development; IGI:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
DR GO; GO:0006417; P:regulation of translation; IMP:MGI.
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; 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_0000076681"
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 406
FT /note="P -> S (in Ref. 5; AAH05454)"
FT /evidence="ECO:0000305"
FT CONFLICT 418
FT /note="S -> N (in Ref. 5; AAH05454)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="S -> T (in Ref. 1; CAA43455)"
FT /evidence="ECO:0000305"
FT CONFLICT 603
FT /note="H -> Y (in Ref. 5; AAH05454)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 889 AA; 98126 MW; 704B8A018EAC6B4C CRC64;
MKNPFAHLAE PLDAAQPGKR FFNLNKLEDS RYGRLPFSIR VLLEAAVRNC DEFLVKKNDI
ENILNWNVMQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGN PEKINPVCPA
DLVIDHSIQV DFNRRADSLQ KNQDLEFERN KERFEFLKWG SQAFCNMRII PPGSGIIHQV
NLEYLARVVF DQDGCYYPDS LVGTDSHTTM IDGLGVLGWG VGGIEAEAVM LGQPISMVLP
QVIGYKLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC
PEYGATAAFF PVDEVSIAYL LQTGREEDKV KHIQKYLQAV GMFRDFNDTS QDPDFTQVVE
LDLKTVVPCC SGPKRPQDKV AVSEMKKDFE SCLGAKQGFK GFQVAPDRHN DRKTFLYSNS
EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVEAG LSVKPYIKTS LSPGSGVVTY
YLRESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG
RVHPNTRANY LASPPLVIAY AIAGTVRIDF EKEPLGVNAQ GRQVFLKDIW PTRDEIQAVE
RQHVIPGMFK EVYQKIETVN KSWNALAAPS EKLYAWNPKS TYIKSPPFFE SLTLDLQPPK
SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAIMA
RGTFANIRLL NKFLNKQAPQ TVHLPSGETL DVFDAAERYQ QAGLPLIVLA GKEYGSGSSR
DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GETADSLGLT GRERYTINIP
EDLKPRMTVQ IKLDTGKTFQ AVMRFDTDVE LTYFHNGGIL NYMIRKMAQ
