Q99798 (ACON_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aconitate hydratase, mitochondrial
Short name=Aconitase
EC=4.2.1.3

Alternative name(s):
Citrate hydro-lyase

Gene names

Name:

ACO2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	780 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the isomerization of citrate to isocitrate via cis-aconitate By similarity.
Catalytic activity	Citrate = isocitrate.
Cofactor	Binds 1 4Fe-4S cluster per subunit. Binding of a 3Fe-4S cluster leads to an inactive enzyme By similarity.
Pathway	Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 2/2.
Subunit structure	Monomer By similarity.
Subcellular location	Mitochondrion By similarity.
Involvement in disease	Infantile cerebellar-retinal degeneration (ICRD) [MIM:614559]: A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Belongs to the aconitase/IPM isomerase family.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration
Domain	Transit peptide
Ligand	4Fe-4S Iron Iron-sulfur Metal-binding
Molecular function	Lyase
PTM	Acetylation Isopeptide bond Phosphoprotein Pyrrolidone carboxylic acid Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW citrate metabolic process Inferred from direct assay Ref.2. Source: MGI isocitrate metabolic process Inferred from electronic annotation. Source: Compara tricarboxylic acid cycle Inferred from direct assay Ref.2. Source: MGI
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	3 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: Compara 4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW citrate hydro-lyase (cis-aconitate-forming) activity Inferred from electronic annotation. Source: EC iron ion binding Inferred from direct assay Ref.2. Source: MGI isocitrate hydro-lyase (cis-aconitate-forming) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 27	27	Mitochondrion By similarity
	Chain	28 – 780	753	Aconitate hydratase, mitochondrial		PRO_0000000541
Regions
	Region	192 – 194	3	Substrate binding By similarity
	Region	670 – 671	2	Substrate binding By similarity
Sites
	Metal binding	385	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	448	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	451	1	Iron-sulfur (4Fe-4S) By similarity
	Binding site	99	1	Substrate By similarity
	Binding site	474	1	Substrate By similarity
	Binding site	479	1	Substrate By similarity
	Binding site	607	1	Substrate By similarity
Amino acid modifications
	Modified residue	28	1	Pyrrolidone carboxylic acid By similarity
	Modified residue	50	1	N6-acetyllysine By similarity
	Modified residue	559	1	Phosphoserine Ref.10
	Modified residue	573	1	N6-acetyllysine Ref.9
	Modified residue	605	1	N6-acetyllysine Ref.9
	Cross-link	144		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	112	1	S → R in ICRD; functional expression studies in yeast show that the mutant has decreased function under growth conditions requiring the TCA cycle and the glyoxylate shunt. Ref.13		VAR_067543
	Natural variant	697	1	T → N in a breast cancer sample; somatic mutation. Ref.12		VAR_036572
	Natural variant	768	1	A → S. Corresponds to variant rs1804785 [ dbSNP | Ensembl ].		VAR_033297
Experimental info
	Sequence conflict	35	1	S → T in AAB38416. Ref.1
	Sequence conflict	136	1	G → D in AAB38416. Ref.1
	Sequence conflict	159	1	A → D in AAB38416. Ref.1
	Sequence conflict	167	1	K → S in AAB38416. Ref.1
	Sequence conflict	199	1	G → D in CAG38805. Ref.4
	Sequence conflict	207	1	G → R in AAH26196. Ref.6
	Sequence conflict	242	1	S → T in AAB38416. Ref.1
	Sequence conflict	270	1	P → H in AAH26196. Ref.6
	Sequence conflict	275	1	I → M in AAB38416. Ref.1
	Sequence conflict	444	1	L → P in CAG38805. Ref.4
	Sequence conflict	517	1	T → K in AAB38416. Ref.1
	Sequence conflict	553	1	G → R in AAB38416. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99798 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 58C9FFBDBDC63D5E	FASTA	780	85,425
	10 20 30 40 50 60 MAPYSLLVTR LQKALGVRQY HVASVLCQRA KVAMSHFEPN EYIHYDLLEK NINIVRKRLN 70 80 90 100 110 120 RPLTLSEKIV YGHLDDPASQ EIERGKSYLR LRPDRVAMQD ATAQMAMLQF ISSGLSKVAV 130 140 150 160 170 180 PSTIHCDHLI EAQVGGEKDL RRAKDINQEV YNFLATAGAK YGVGFWKPGS GIIHQIILEN 190 200 210 220 230 240 YAYPGVLLIG TDSHTPNGGG LGGICIGVGG ADAVDVMAGI PWELKCPKVI GVKLTGSLSG 250 260 270 280 290 300 WSSPKDVILK VAGILTVKGG TGAIVEYHGP GVDSISCTGM ATICNMGAEI GATTSVFPYN 310 320 330 340 350 360 HRMKKYLSKT GREDIANLAD EFKDHLVPDP GCHYDQLIEI NLSELKPHIN GPFTPDLAHP 370 380 390 400 410 420 VAEVGKVAEK EGWPLDIRVG LIGSCTNSSY EDMGRSAAVA KQALAHGLKC KSQFTITPGS 430 440 450 460 470 480 EQIRATIERD GYAQILRDLG GIVLANACGP CIGQWDRKDI KKGEKNTIVT SYNRNFTGRN 490 500 510 520 530 540 DANPETHAFV TSPEIVTALA IAGTLKFNPE TDYLTGTDGK KFRLEAPDAD ELPKGEFDPG 550 560 570 580 590 600 QDTYQHPPKD SSGQHVDVSP TSQRLQLLEP FDKWDGKDLE DLQILIKVKG KCTTDHISAA 610 620 630 640 650 660 GPWLKFRGHL DNISNNLLIG AINIENGKAN SVRNAVTQEF GPVPDTARYY KKHGIRWVVI 670 680 690 700 710 720 GDENYGEGSS REHAALEPRH LGGRAIITKS FARIHETNLK KQGLLPLTFA DPADYNKIHP 730 740 750 760 770 780 VDKLTIQGLK DFTPGKPLKC IIKHPNGTQE TILLNHTFNE TQIEWFRAGS ALNRMKELQQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and structural characterization of human mitochondrial aconitase." Juang H.H., Chiou B. Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"Characterization of the human mitochondrial aconitase gene (ACO2)." Mirel D.B., Marder K., Graziano J., Freyer G., Zhao Q., Mayeux R., Wilhelmsen K.C. Gene 213:205-218(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Uterus.
[7]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 69-84; 234-245; 313-323; 379-395; 412-424; 430-437; 507-520; 565-573; 608-628; 634-648 AND 657-671, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[8]	"Purification and partial amino acid sequence of human aconitase." Baldwin G.S., Seet K.L., Callaghan J., Toncich G., Toh B.H., Moritz R.L., Rubira M.R., Simpson R. Protein Seq. Data Anal. 4:63-67(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 69-83; 96-107; 371-396 AND 524-534.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-573 AND LYS-605, MASS SPECTROMETRY.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-559, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-697.
[13]	"Infantile Cerebellar-Retinal Degeneration Associated with a Mutation in Mitochondrial Aconitase, ACO2." Spiegel R., Pines O., Ta-Shma A., Burak E., Shaag A., Halvardson J., Edvardson S., Mahajna M., Zenvirt S., Saada A., Shalev S., Feuk L., Elpeleg O. Am. J. Hum. Genet. 90:518-523(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ICRD ARG-112, CHARACTERIZATION OF VARIANT ICRD ARG-112.
+	Additional computationally mapped references.

Web resources

Wikipedia

Aconitase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	U80040 mRNA. Translation: AAB38416.1. U87939 , U87926, U87927, U87928, U87929, U87930, U87931, U87932, U87933, U87934, U87935, U87936, U87937, U87938 Genomic DNA. Translation: AAC39921.1. CR456365 mRNA. Translation: CAG30251.1. CR536568 mRNA. Translation: CAG38805.1. AL023553, AL008582 Genomic DNA. Translation: CAI20278.1. AL008582, AL023553 Genomic DNA. Translation: CAI17931.1. BC014092 mRNA. Translation: AAH14092.1. BC026196 mRNA. Translation: AAH26196.1.
IPI	IPI00017855.
PIR	S17526. T52543.
RefSeq	NP_001089.1. NM_001098.2.
UniGene	Hs.643610.
3D structure databases
ProteinModelPortal	Q99798.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99798. 2 interactions.
MINT	MINT-2856402.
STRING	9606.ENSP00000216254.
PTM databases
PhosphoSite	Q99798.
Polymorphism databases
DMDM	6686275.
2D gel databases
DOSAC-COBS-2DPAGE	Q99798.
REPRODUCTION-2DPAGE	IPI00017855. Q99798.
SWISS-2DPAGE	Q99798.
UCD-2DPAGE	Q99798.
Proteomic databases
PaxDb	Q99798.
PRIDE	Q99798.
Protocols and materials databases
DNASU	50.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216254; ENSP00000216254; ENSG00000100412.
GeneID	50.
KEGG	hsa:50.
UCSC	uc003bac.3. human.
Organism-specific databases
CTD	50.
GeneCards	GC22P041865.
HGNC	HGNC:118. ACO2.
HPA	HPA001097.
MIM	100850. gene. 614559. phenotype.
neXtProt	NX_Q99798.
PharmGKB	PA24443.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1048.
HOGENOM	HOG000224293.
HOVERGEN	HBG000248.
KO	K01681.
OrthoDB	EOG4BCDM9.
PhylomeDB	Q99798.
Enzyme and pathway databases
BioCyc	MetaCyc:HS02077-MONOMER.
Reactome	REACT_111217. Metabolism. REACT_17015. Metabolism of proteins.
UniPathway	UPA00223; UER00718.
Gene expression databases
ArrayExpress	Q99798.
Bgee	Q99798.
CleanEx	HS_ACO2.
Genevestigator	Q99798.
GermOnline	ENSG00000100412. Homo sapiens.
Family and domain databases
Gene3D	3.20.19.10. 1 hit. 3.30.499.10. 2 hits. 3.40.1060.10. 1 hit.
InterPro	IPR015931. Acnase/IPM_dHydase_lsu_aba_1/3. IPR015937. Acoase/IPM_deHydtase. IPR001030. Acoase/IPM_deHydtase_lsu_aba. IPR015928. Aconitase/3IPM_dehydase_swvl. IPR015932. Aconitase/IPMdHydase_lsu_aba_2. IPR018136. Aconitase_4Fe-4S_BS. IPR006248. Aconitase_mito-like. IPR000573. AconitaseA/IPMdHydase_ssu_swvl. [Graphical view]
PANTHER	PTHR11670. PTHR11670. 1 hit. PTHR11670:SF5. PTHR11670:SF5. 1 hit.
Pfam	PF00330. Aconitase. 1 hit. PF00694. Aconitase_C. 1 hit. [Graphical view]
PRINTS	PR00415. ACONITASE.
SUPFAM	SSF52016. Aconitase/3IPM_dehydase_swvl. 1 hit. SSF53732. Aconitase_N. 1 hit.
TIGRFAMs	TIGR01340. aconitase_mito. 1 hit.
PROSITE	PS00450. ACONITASE_1. 1 hit. PS01244. ACONITASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ACO2. human.
GenomeRNAi	50.
NextBio	195.
SOURCE	Search...

Entry information

Entry name

ACON_HUMAN

Accession

Primary (citable) accession number: Q99798
Secondary accession number(s): O75809 , Q5JZ41, Q6FHX0, Q8TAQ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.