ID ACON_HUMAN Reviewed; 780 AA. AC Q99798; O75809; Q5JZ41; Q6FHX0; Q8TAQ6; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 02-OCT-2024, entry version 222. 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Skeletal muscle; RA Juang H.H., Chiou B.; RT "Cloning and structural characterization of human mitochondrial RT aconitase."; RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9630632; DOI=10.1016/s0378-1119(98)00188-7; RA Mirel D.B., Marder K., Graziano J., Freyer G., Zhao Q., Mayeux R., RA Wilhelmsen K.C.; RT "Characterization of the human mitochondrial aconitase gene (ACO2)."; RL Gene 213:205-218(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Uterus; 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 [7] RP PROTEIN SEQUENCE OF 69-84; 234-245; 313-323; 379-395; 412-424; 430-437; RP 507-520; 565-573; 608-628; 634-648 AND 657-671, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [8] RP PROTEIN SEQUENCE OF 69-83; 96-107; 371-396 AND 524-534. RX PubMed=1946331; RA Baldwin G.S., Seet K.L., Callaghan J., Toncich G., Toh B.H., Moritz R.L., RA Rubira M.R., Simpson R.; RT "Purification and partial amino acid sequence of human aconitase."; RL Protein Seq. Data Anal. 4:63-67(1991). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-573 AND LYS-605, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-559, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-559, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP INVOLVEMENT IN OPA9, INVOLVEMENT IN ICRD, VARIANTS OPA9 VAL-74 AND ARG-661, RP AND VARIANTS ICRD ASP-259 AND ASN-736. RX PubMed=25351951; DOI=10.1136/jmedgenet-2014-102532; RA Metodiev M.D., Gerber S., Hubert L., Delahodde A., Chretien D., Gerard X., RA Amati-Bonneau P., Giacomotto M.C., Boddaert N., Kaminska A., Desguerre I., RA Amiel J., Rio M., Kaplan J., Munnich A., Rotig A., Rozet J.M., Besmond C.; RT "Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause RT either isolated or syndromic optic neuropathy with encephalopathy and RT cerebellar atrophy."; RL J. Med. Genet. 51:834-838(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [16] RP VARIANT [LARGE SCALE ANALYSIS] ASN-697. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [17] RP VARIANT ICRD ARG-112, AND CHARACTERIZATION OF VARIANT ICRD ARG-112. RX PubMed=22405087; DOI=10.1016/j.ajhg.2012.01.009; RA Spiegel R., Pines O., Ta-Shma A., Burak E., Shaag A., Halvardson J., RA Edvardson S., Mahajna M., Zenvirt S., Saada A., Shalev S., Feuk L., RA Elpeleg O.; RT "Infantile cerebellar-retinal degeneration associated with a mutation in RT mitochondrial aconitase, ACO2."; RL Am. J. Hum. Genet. 90:518-523(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: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 -!- DISEASE: Infantile cerebellar-retinal degeneration (ICRD) [MIM:614559]: CC A severe autosomal recessive neurodegenerative disorder characterized CC by onset between ages 2 and 6 months of truncal hypotonia, athetosis, CC seizures, and ophthalmologic abnormalities, particularly optic atrophy CC and retinal degeneration. Affected individuals show profound CC psychomotor retardation, with only some achieving rolling, sitting, or CC recognition of family. Brain MRI shows progressive cerebral and CC cerebellar degeneration. {ECO:0000269|PubMed:22405087, CC ECO:0000269|PubMed:25351951}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Optic atrophy 9 (OPA9) [MIM:616289]: A condition that features CC progressive visual loss in association with optic atrophy. Atrophy of CC the optic disk indicates a deficiency in the number of nerve fibers CC which arise in the retina and converge to form the optic disk, optic CC nerve, optic chiasm and optic tracts. {ECO:0000269|PubMed:25351951}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Aconitase entry; CC URL="https://en.wikipedia.org/wiki/Aconitase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U80040; AAB38416.1; -; mRNA. DR EMBL; U87939; AAC39921.1; -; Genomic_DNA. DR EMBL; U87926; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87927; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87928; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87929; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87930; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87931; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87932; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87933; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87934; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87935; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87936; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87937; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; U87938; AAC39921.1; JOINED; Genomic_DNA. DR EMBL; CR456365; CAG30251.1; -; mRNA. DR EMBL; CR536568; CAG38805.1; -; mRNA. DR EMBL; AL023553; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL008582; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC014092; AAH14092.1; -; mRNA. DR EMBL; BC026196; AAH26196.1; -; mRNA. DR CCDS; CCDS14017.1; -. DR PIR; S17526; S17526. DR PIR; T52543; T52543. DR RefSeq; NP_001089.1; NM_001098.2. DR AlphaFoldDB; Q99798; -. DR SMR; Q99798; -. DR BioGRID; 106566; 219. DR IntAct; Q99798; 17. DR MINT; Q99798; -. DR STRING; 9606.ENSP00000216254; -. DR DrugBank; DB03964; 4-Hydroxy-Aconitate Ion. DR DrugBank; DB04351; Aconitate Ion. DR DrugBank; DB04072; Alpha-Methylisocitric Acid. DR DrugBank; DB01727; Isocitric Acid. DR DrugBank; DB04562; Tricarballylic acid. DR CarbonylDB; Q99798; -. DR GlyCosmos; Q99798; 1 site, 1 glycan. DR GlyGen; Q99798; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q99798; -. DR PhosphoSitePlus; Q99798; -. DR SwissPalm; Q99798; -. DR BioMuta; ACO2; -. DR DMDM; 6686275; -. DR REPRODUCTION-2DPAGE; IPI00017855; -. DR REPRODUCTION-2DPAGE; Q99798; -. DR CPTAC; CPTAC-2717; -. DR jPOST; Q99798; -. DR MassIVE; Q99798; -. DR PaxDb; 9606-ENSP00000216254; -. DR PeptideAtlas; Q99798; -. DR ProteomicsDB; 78478; -. DR Pumba; Q99798; -. DR Antibodypedia; 240; 590 antibodies from 40 providers. DR DNASU; 50; -. DR Ensembl; ENST00000216254.9; ENSP00000216254.4; ENSG00000100412.17. DR GeneID; 50; -. DR KEGG; hsa:50; -. DR MANE-Select; ENST00000216254.9; ENSP00000216254.4; NM_001098.3; NP_001089.1. DR UCSC; uc003bac.3; human. DR AGR; HGNC:118; -. DR CTD; 50; -. DR DisGeNET; 50; -. DR GeneCards; ACO2; -. DR HGNC; HGNC:118; ACO2. DR HPA; ENSG00000100412; Tissue enhanced (heart muscle, skeletal muscle, tongue). DR MalaCards; ACO2; -. DR MIM; 100850; gene. DR MIM; 614559; phenotype. DR MIM; 616289; phenotype. DR neXtProt; NX_Q99798; -. DR OpenTargets; ENSG00000100412; -. DR Orphanet; 98676; Autosomal recessive isolated optic atrophy. DR Orphanet; 313850; Infantile cerebellar-retinal degeneration. DR PharmGKB; PA24443; -. DR VEuPathDB; HostDB:ENSG00000100412; -. DR eggNOG; KOG0453; Eukaryota. DR GeneTree; ENSGT00940000154892; -. DR HOGENOM; CLU_006714_2_2_1; -. DR InParanoid; Q99798; -. DR OrthoDB; 3266779at2759; -. DR PhylomeDB; Q99798; -. DR TreeFam; TF300627; -. DR BioCyc; MetaCyc:HS02077-MONOMER; -. DR BRENDA; 4.2.1.3; 2681. DR PathwayCommons; Q99798; -. DR Reactome; R-HSA-1268020; Mitochondrial protein import. DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle). DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR Reactome; R-HSA-9854311; Maturation of TCA enzymes and regulation of TCA cycle. DR SignaLink; Q99798; -. DR SIGNOR; Q99798; -. DR UniPathway; UPA00223; UER00718. DR BioGRID-ORCS; 50; 406 hits in 1181 CRISPR screens. DR ChiTaRS; ACO2; human. DR GenomeRNAi; 50; -. DR Pharos; Q99798; Tbio. DR PRO; PR:Q99798; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q99798; protein. DR Bgee; ENSG00000100412; Expressed in heart right ventricle and 201 other cell types or tissues. DR ExpressionAtlas; Q99798; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB. DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; IEA:Ensembl. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central. DR GO; GO:0003994; F:aconitate hydratase activity; IBA:GO_Central. DR GO; GO:0005506; F:iron ion binding; IDA:MGI. DR GO; GO:0006101; P:citrate metabolic process; IDA:MGI. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0006102; P:isocitrate metabolic process; IEA:Ensembl. 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; IDA:MGI. DR CDD; cd01578; AcnA_Mitochon_Swivel; 1. DR CDD; cd01584; AcnA_Mitochondrial; 1. DR Gene3D; 3.40.1060.10; Aconitase, Domain 2; 1. DR Gene3D; 3.30.499.10; Aconitase, domain 3; 2. DR Gene3D; 3.20.19.10; Aconitase, domain 4; 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; IPR050926; Aconitase/IPM_isomerase. 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 NCBIfam; TIGR01340; aconitase_mito; 1. DR PANTHER; PTHR43160; ACONITATE HYDRATASE B; 1. DR PANTHER; PTHR43160:SF3; ACONITATE HYDRATASE, MITOCHONDRIAL; 1. DR Pfam; PF00330; Aconitase; 1. DR Pfam; PF00694; Aconitase_C; 1. DR PRINTS; PR00415; ACONITASE. DR SUPFAM; SSF53732; Aconitase iron-sulfur domain; 1. DR SUPFAM; SSF52016; LeuD/IlvD-like; 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; Disease variant; Iron; KW Iron-sulfur; Lyase; Metal-binding; Mitochondrion; Neurodegeneration; KW Phosphoprotein; Proteomics identification; 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_0000000541" FT REGION 528..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 549 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99KI0" FT MOD_RES 559 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 573 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" 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:0007744|PubMed:19608861" 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 739 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 VARIANT 74 FT /note="L -> V (in OPA9; dbSNP:rs141772938)" FT /evidence="ECO:0000269|PubMed:25351951" FT /id="VAR_073435" FT VARIANT 112 FT /note="S -> R (in ICRD; functional expression studies in FT yeast show that the mutant has decreased function under FT growth conditions requiring the TCA cycle and the FT glyoxylate shunt; dbSNP:rs786200924)" FT /evidence="ECO:0000269|PubMed:22405087" FT /id="VAR_067543" FT VARIANT 259 FT /note="G -> D (in ICRD; dbSNP:rs786204828)" FT /evidence="ECO:0000269|PubMed:25351951" FT /id="VAR_073436" FT VARIANT 661 FT /note="G -> R (in OPA9; dbSNP:rs752034900)" FT /evidence="ECO:0000269|PubMed:25351951" FT /id="VAR_073437" FT VARIANT 697 FT /note="T -> N (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036572" FT VARIANT 736 FT /note="K -> N (in ICRD; dbSNP:rs786204829)" FT /evidence="ECO:0000269|PubMed:25351951" FT /id="VAR_073438" FT VARIANT 768 FT /note="A -> S (in dbSNP:rs1804785)" FT /id="VAR_033297" FT CONFLICT 35 FT /note="S -> T (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 136 FT /note="G -> D (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 159 FT /note="A -> D (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 167 FT /note="K -> S (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 199 FT /note="G -> D (in Ref. 4; CAG38805)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="G -> R (in Ref. 6; AAH26196)" FT /evidence="ECO:0000305" FT CONFLICT 242 FT /note="S -> T (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 270 FT /note="P -> H (in Ref. 6; AAH26196)" FT /evidence="ECO:0000305" FT CONFLICT 275 FT /note="I -> M (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 444 FT /note="L -> P (in Ref. 4; CAG38805)" FT /evidence="ECO:0000305" FT CONFLICT 517 FT /note="T -> K (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" FT CONFLICT 553 FT /note="G -> R (in Ref. 1; AAB38416)" FT /evidence="ECO:0000305" SQ SEQUENCE 780 AA; 85425 MW; 58C9FFBDBDC63D5E CRC64; MAPYSLLVTR LQKALGVRQY HVASVLCQRA KVAMSHFEPN EYIHYDLLEK NINIVRKRLN RPLTLSEKIV YGHLDDPASQ EIERGKSYLR LRPDRVAMQD ATAQMAMLQF ISSGLSKVAV PSTIHCDHLI EAQVGGEKDL RRAKDINQEV YNFLATAGAK YGVGFWKPGS GIIHQIILEN YAYPGVLLIG TDSHTPNGGG LGGICIGVGG ADAVDVMAGI PWELKCPKVI GVKLTGSLSG WSSPKDVILK VAGILTVKGG TGAIVEYHGP GVDSISCTGM ATICNMGAEI GATTSVFPYN HRMKKYLSKT GREDIANLAD EFKDHLVPDP GCHYDQLIEI NLSELKPHIN GPFTPDLAHP VAEVGKVAEK EGWPLDIRVG LIGSCTNSSY EDMGRSAAVA KQALAHGLKC KSQFTITPGS EQIRATIERD GYAQILRDLG GIVLANACGP CIGQWDRKDI KKGEKNTIVT SYNRNFTGRN DANPETHAFV TSPEIVTALA IAGTLKFNPE TDYLTGTDGK KFRLEAPDAD ELPKGEFDPG QDTYQHPPKD SSGQHVDVSP TSQRLQLLEP FDKWDGKDLE DLQILIKVKG KCTTDHISAA GPWLKFRGHL DNISNNLLIG AINIENGKAN SVRNAVTQEF GPVPDTARYY KKHGIRWVVI GDENYGEGSS REHAALEPRH LGGRAIITKS FARIHETNLK KQGLLPLTFA DPADYNKIHP VDKLTIQGLK DFTPGKPLKC IIKHPNGTQE TILLNHTFNE TQIEWFRAGS ALNRMKELQQ //