ACON_MOUSE
ID ACON_MOUSE Reviewed; 780 AA.
AC Q99KI0; Q3UDK9; Q3ULG9; Q3UNH7; Q505P4;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Aconitate hydratase, mitochondrial;
DE Short=Aconitase;
DE EC=4.2.1.3 {ECO:0000250|UniProtKB:P16276};
DE AltName: Full=Citrate hydro-lyase;
DE Flags: Precursor;
GN Name=Aco2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Mammary tumor;
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 [3]
RP PROTEIN SEQUENCE OF 32-56; 59-84; 96-138; 143-160; 234-245; 251-258;
RP 313-323; 371-395; 402-409; 412-424; 430-457; 466-474; 480-517; 522-587;
RP 592-605; 608-628; 634-648; 657-671; 694-739 AND 744-767, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, AND IDENTIFICATION BY
RP 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).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-50 AND LYS-144, SUCCINYLATION
RP [LARGE SCALE ANALYSIS] AT LYS-31; LYS-50; LYS-138; LYS-144; LYS-233;
RP LYS-411; LYS-517; LYS-523; LYS-549; LYS-573; LYS-577; LYS-591; LYS-605;
RP LYS-628; LYS-689; LYS-723 AND LYS-730, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-50; LYS-138; LYS-144; LYS-233;
RP LYS-517; LYS-523; LYS-605; LYS-723; LYS-730; LYS-736; LYS-739 AND LYS-743,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Catalyzes the isomerization of citrate to isocitrate via cis-
CC aconitate. {ECO:0000250|UniProtKB:P16276}.
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:P16276};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P16276};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. Binding of a [3Fe-4S]
CC cluster leads to an inactive enzyme. {ECO:0000250|UniProtKB:P16276};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC from oxaloacetate: step 2/2.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P16276}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P16276}.
CC -!- PTM: Forms covalent cross-links mediated by transglutaminase TGM2,
CC between a glutamine and the epsilon-amino group of a lysine residue,
CC forming homopolymers and heteropolymers.
CC {ECO:0000250|UniProtKB:Q9ER34}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; AK143917; BAE25602.1; -; mRNA.
DR EMBL; AK144207; BAE25770.1; -; mRNA.
DR EMBL; AK145511; BAE26479.1; -; mRNA.
DR EMBL; AK150027; BAE29252.1; -; mRNA.
DR EMBL; AK165411; BAE38169.1; -; mRNA.
DR EMBL; BC004645; AAH04645.1; -; mRNA.
DR EMBL; BC094462; AAH94462.1; -; mRNA.
DR CCDS; CCDS27675.1; -.
DR RefSeq; NP_542364.1; NM_080633.2.
DR AlphaFoldDB; Q99KI0; -.
DR SMR; Q99KI0; -.
DR BioGRID; 197925; 69.
DR IntAct; Q99KI0; 8.
DR MINT; Q99KI0; -.
DR STRING; 10090.ENSMUSP00000023116; -.
DR CarbonylDB; Q99KI0; -.
DR iPTMnet; Q99KI0; -.
DR PhosphoSitePlus; Q99KI0; -.
DR SwissPalm; Q99KI0; -.
DR REPRODUCTION-2DPAGE; Q99KI0; -.
DR EPD; Q99KI0; -.
DR jPOST; Q99KI0; -.
DR MaxQB; Q99KI0; -.
DR PaxDb; Q99KI0; -.
DR PeptideAtlas; Q99KI0; -.
DR PRIDE; Q99KI0; -.
DR ProteomicsDB; 285596; -.
DR Antibodypedia; 240; 527 antibodies from 39 providers.
DR DNASU; 11429; -.
DR Ensembl; ENSMUST00000023116; ENSMUSP00000023116; ENSMUSG00000022477.
DR GeneID; 11429; -.
DR KEGG; mmu:11429; -.
DR UCSC; uc007wxp.1; mouse.
DR CTD; 50; -.
DR MGI; MGI:87880; Aco2.
DR VEuPathDB; HostDB:ENSMUSG00000022477; -.
DR eggNOG; KOG0453; Eukaryota.
DR GeneTree; ENSGT00940000154892; -.
DR HOGENOM; CLU_006714_2_2_1; -.
DR InParanoid; Q99KI0; -.
DR OMA; GCIGMGQ; -.
DR OrthoDB; 190960at2759; -.
DR PhylomeDB; Q99KI0; -.
DR TreeFam; TF300627; -.
DR BRENDA; 4.2.1.3; 3474.
DR Reactome; R-MMU-71403; Citric acid cycle (TCA cycle).
DR UniPathway; UPA00223; UER00718.
DR BioGRID-ORCS; 11429; 16 hits in 73 CRISPR screens.
DR ChiTaRS; Aco2; mouse.
DR PRO; PR:Q99KI0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q99KI0; protein.
DR Bgee; ENSMUSG00000022477; Expressed in cardiac muscle of left ventricle and 271 other tissues.
DR ExpressionAtlas; Q99KI0; baseline and differential.
DR Genevisible; Q99KI0; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; ISO:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISO:MGI.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:MGI.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; ISO:MGI.
DR GO; GO:0006101; P:citrate metabolic process; ISO:MGI.
DR GO; GO:0006102; P:isocitrate metabolic process; ISO:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0035900; P:response to isolation stress; IEA:Ensembl.
DR GO; GO:0006099; P:tricarboxylic acid cycle; ISO:MGI.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 2.
DR Gene3D; 3.40.1060.10; -; 1.
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; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR015932; Aconitase_dom2.
DR InterPro; IPR006248; Aconitase_mito-like.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01340; aconitase_mito; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Acetylation; Direct protein sequencing; Iron; Iron-sulfur; Lyase;
KW Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome;
KW Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 28..780
FT /note="Aconitate hydratase, mitochondrial"
FT /id="PRO_0000000542"
FT REGION 524..560
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..560
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 192..194
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 385
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 448
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 451
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 474
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 479
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 607
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 670..671
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 31
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 50
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753,
FT ECO:0007744|PubMed:23806337"
FT MOD_RES 50
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 138
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 138
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 144
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753,
FT ECO:0007744|PubMed:23806337"
FT MOD_RES 144
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 233
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 233
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 411
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 517
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 517
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 523
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 523
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 549
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99798"
FT MOD_RES 573
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99798"
FT MOD_RES 573
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 577
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 591
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 605
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 605
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 628
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 689
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 723
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 723
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 730
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 730
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 736
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 739
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 743
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 7..8
FT /note="LV -> P (in Ref. 1; BAE25770)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="L -> F (in Ref. 2; AAH94462)"
FT /evidence="ECO:0000305"
FT CONFLICT 758
FT /note="F -> L (in Ref. 1; BAE29252)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 780 AA; 85464 MW; 9B515846E875D581 CRC64;
MAPYSLLVTR LQKALGVRQY HVASVLCQRA KVAMSHFEPS EYIRYDLLEK NINIVRKRLN
RPLTLSEKIV YGHLDDPANQ EIERGKTYLR LRPDRVAMQD ATAQMAMLQF ISSGLPKVAV
PSTIHCDHLI EAQVGGEKDL RRAKDINQEV YNFLATAGAK YGVGFWRPGS GIIHQIILEN
YAYPGVLLIG TDSHTPNGGG LGGICIGVGG ADAVDVMAGI PWELKCPKVI GVKLTGSLSG
WTSPKDVILK VAGILTVKGG TGAIVEYHGP GVDSISCTGM ATICNMGAEI GATTSVFPYN
HRMKKYLSKT GRTDIANLAE EFKDHLVPDP GCQYDQVIEI NLNELKPHIN GPFTPDLAHP
VADVGTVAEK EGWPLDIRVG LIGSCTNSSY EDMGRSAAVA KQALAHGLKC KSQFTITPGS
EQIRATIERD GYAQILRDVG GIVLANACGP CIGQWDRKDI KKGEKNTIVT SYNRNFTGRN
DANPETHAFV TSPEIVTALA IAGTLKFNPE TDFLTGKDGK KFKLEAPDAD ELPRSDFDPG
QDTYQHPPKD SSGQRVDVSP TSQRLQLLEP FDKWDGKDLE DLQILIKVKG KCTTDHISAA
GPWLKFRGHL DNISNNLLIG AINIENGKAN SVRNAVTQEF GPVPDTARYY KKHGIRWVVI
GDENYGEGSS REHAALEPRH LGGRAIITKS FARIHETNLK KQGLLPLTFA DPSDYNKIHP
VDKLTIQGLK DFAPGKPLKC VIKHPNGTQE TILLNHTFNE TQIEWFRAGS ALNRMKELQQ
