ACON_RAT
ID ACON_RAT Reviewed; 780 AA.
AC Q9ER34; Q6P6V3;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 148.
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 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].
RC TISSUE=Heart;
RA Wieland A., Bruss M.;
RT "Molecular cloning of the rat heart mitochondrial aconitase.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 32-44; 59-84; 96-138; 143-160; 234-245; 251-302;
RP 313-323; 371-395; 402-409; 412-424; 430-458; 466-474; 480-517; 522-587;
RP 592-628; 634-648; 657-679 AND 694-767, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Diao W., Kang S.U., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP TRANSGLUTAMINATION.
RX PubMed=16341586; DOI=10.1007/s11064-005-8796-x;
RA Kim S.Y., Marekov L., Bubber P., Browne S.E., Stavrovskaya I., Lee J.,
RA Steinert P.M., Blass J.P., Beal M.F., Gibson G.E., Cooper A.J.;
RT "Mitochondrial aconitase is a transglutaminase 2 substrate:
RT transglutamination is a probable mechanism contributing to high-molecular-
RT weight aggregates of aconitase and loss of aconitase activity in Huntington
RT disease brain.";
RL Neurochem. Res. 30:1245-1255(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-559, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:0000269|PubMed:16341586}.
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. {ECO:0000269|PubMed:16341586}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; AJ243266; CAC11018.1; -; mRNA.
DR EMBL; BC061999; AAH61999.1; -; mRNA.
DR RefSeq; NP_077374.2; NM_024398.2.
DR AlphaFoldDB; Q9ER34; -.
DR SMR; Q9ER34; -.
DR BioGRID; 249448; 6.
DR IntAct; Q9ER34; 4.
DR MINT; Q9ER34; -.
DR STRING; 10116.ENSRNOP00000029144; -.
DR CarbonylDB; Q9ER34; -.
DR iPTMnet; Q9ER34; -.
DR PhosphoSitePlus; Q9ER34; -.
DR SwissPalm; Q9ER34; -.
DR World-2DPAGE; 0004:Q9ER34; -.
DR jPOST; Q9ER34; -.
DR PaxDb; Q9ER34; -.
DR PRIDE; Q9ER34; -.
DR Ensembl; ENSRNOT00000038612; ENSRNOP00000029144; ENSRNOG00000024128.
DR GeneID; 79250; -.
DR KEGG; rno:79250; -.
DR UCSC; RGD:621360; rat.
DR CTD; 50; -.
DR RGD; 621360; Aco2.
DR eggNOG; KOG0453; Eukaryota.
DR GeneTree; ENSGT00940000154892; -.
DR HOGENOM; CLU_006714_2_2_1; -.
DR InParanoid; Q9ER34; -.
DR OMA; GCIGMGQ; -.
DR OrthoDB; 190960at2759; -.
DR PhylomeDB; Q9ER34; -.
DR TreeFam; TF300627; -.
DR BRENDA; 4.2.1.3; 5301.
DR Reactome; R-RNO-71403; Citric acid cycle (TCA cycle).
DR SABIO-RK; Q9ER34; -.
DR UniPathway; UPA00223; UER00718.
DR PRO; PR:Q9ER34; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000024128; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q9ER34; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; IDA:RGD.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:RGD.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:RGD.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; ISO:RGD.
DR GO; GO:0006101; P:citrate metabolic process; IDA:RGD.
DR GO; GO:0006102; P:isocitrate metabolic process; IDA:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0035900; P:response to isolation stress; IEP:RGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:RGD.
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_0000000544"
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:0000250|UniProtKB:Q99KI0"
FT MOD_RES 50
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 50
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 138
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 138
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 144
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 144
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 233
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 233
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 411
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 517
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 517
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 523
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 523
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 549
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:0000250|UniProtKB:Q99KI0"
FT MOD_RES 577
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 591
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 605
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99798"
FT MOD_RES 605
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 628
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 689
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 723
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 723
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 730
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 730
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 736
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT MOD_RES 743
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KI0"
FT CONFLICT 224
FT /note="L -> P (in Ref. 1; CAC11018)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="S -> P (in Ref. 1; CAC11018)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="L -> Q (in Ref. 1; CAC11018)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="V -> M (in Ref. 1; CAC11018)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 780 AA; 85433 MW; E523564299DD38BD CRC64;
MAPYSLLVTR LQKALGVRQY HVASALCQRA KVAMSHFEPS EYIRYDLLEK NINIVRKRLN
RPLTLSEKIV YGHLDDPANQ EIERGKTYLR LRPDRVAMQD ATAQMAMLQF ISSGLPKVAV
PSTIHCDHLI EAQLGGEKDL RRAKDINQEV YNFLATAGAK YGVGFWRPGS GIIHQIILEN
YAYPGVLLIG TDSHTPNGGG LGGICIGVGG ADAVDVMAGI PWELKCPKVI GVKLTGTLSG
WTSPKDVILK VAGILTVKGG TGAIVEYHGP GVDSISCTGM ATICNMGAEI GATTSVFPYN
HRMKKYLSKT GRADIANLAE 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 DFAPGKPLNC IIKHPNGTQE TILLNHTFNE TQIEWFRAGS ALNRMKELQQ
