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Identification
HMDB Protein ID HMDBP00038
Secondary Accession Numbers
  • 5267
  • HMDBP04584
Name Acetyl-CoA acetyltransferase, mitochondrial
Synonyms
  1. Acetoacetyl-CoA thiolase
  2. T2
Gene Name ACAT1
Protein Type Enzyme
Biological Properties
General Function Involved in transferase activity, transferring acyl groups other than amino-acyl groups
Specific Function Plays a major role in ketone body metabolism.
Pathways
  • 2-aminoadipic 2-oxoadipic aciduria
  • 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
  • 3-hydroxyisobutyric acid dehydrogenase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-Methylcrotonyl Coa Carboxylase Deficiency Type I
  • 3-Methylglutaconic Aciduria Type I
  • 3-Methylglutaconic Aciduria Type III
  • 3-Methylglutaconic Aciduria Type IV
  • Beta-Ketothiolase Deficiency
  • Butanoate metabolism
  • Butyrate Metabolism
  • Carnitine palmitoyl transferase deficiency (I)
  • Carnitine palmitoyl transferase deficiency (II)
  • Ethylmalonic Encephalopathy
  • Fatty acid Metabolism
  • fatty acid metabolism
  • Glutaric Aciduria Type I
  • Glutaric Aciduria Type I
  • Glyoxylate and dicarboxylate metabolism
  • Hyperlysinemia I, Familial
  • Hyperlysinemia II or Saccharopinuria
  • Isobutyryl-coa dehydrogenase deficiency
  • Isovaleric acidemia
  • Isovaleric Aciduria
  • Ketone Body Metabolism
  • Leigh Syndrome
  • Long chain acyl-CoA dehydrogenase deficiency (LCAD)
  • Lysine Degradation
  • Lysine degradation
  • Malonic Aciduria
  • Malonyl-coa decarboxylase deficiency
  • Maple Syrup Urine Disease
  • Medium chain acyl-coa dehydrogenase deficiency (MCAD)
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency
  • Methylmalonic Aciduria
  • Methylmalonic Aciduria Due to Cobalamin-Related Disorders
  • Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids
  • Primary hyperoxaluria II, PH2
  • Propanoate Metabolism
  • Propanoate metabolism
  • Propionic Acidemia
  • Pyridoxine dependency with seizures
  • Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency)
  • Pyruvate Dehydrogenase Complex Deficiency
  • Pyruvate kinase deficiency
  • Pyruvate Metabolism
  • Pyruvate metabolism
  • Saccharopinuria/Hyperlysinemia II
  • Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency)
  • Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD)
  • Succinyl CoA: 3-ketoacid CoA transferase deficiency
  • Synthesis and degradation of ketone bodies
  • Terpenoid backbone biosynthesis
  • Trifunctional protein deficiency
  • Tryptophan metabolism
  • Valine, Leucine and Isoleucine Degradation
  • Valine, leucine and isoleucine degradation
  • Very-long-chain acyl coa dehydrogenase deficiency (VLCAD)
Reactions
Acetyl-CoA → Coenzyme A + Acetoacetyl-CoA details
Acetyl-CoA + Butyryl-CoA → Coenzyme A + 3-Oxohexanoyl-CoA details
GO Classification
Biological Process
branched-chain amino acid catabolic process
cellular nitrogen compound metabolic process
response to hormone stimulus
ketone body biosynthetic process
ketone body catabolic process
adipose tissue development
liver development
response to starvation
protein homooligomerization
brain development
response to organic cyclic compound
cellular lipid metabolic process
metanephric proximal convoluted tubule development
Cellular Component
mitochondrial matrix
mitochondrial inner membrane
Function
catalytic activity
transferase activity
transferase activity, transferring acyl groups
transferase activity, transferring acyl groups other than amino-acyl groups
Molecular Function
metal ion binding
acetyl-CoA C-acetyltransferase activity
coenzyme binding
Process
metabolic process
Cellular Location
  1. Mitochondrion
Gene Properties
Chromosome Location 11
Locus 11q22.3
SNPs ACAT1
Gene Sequence
>1284 bp
ATGGCTGTGCTGGCGGCACTTCTGCGCAGCGGCGCCCGCAGCCGCAGCCCCCTGCTCCGG
AGGCTGGTGCAGGAAATAAGATATGTGGAACGGAGTTATGTATCAAAACCCACTTTGAAG
GAAGTGGTCATAGTAAGTGCTACAAGAACACCCATTGGATCTTTTTTAGGCAGCCTTTCC
TTGCTGCCAGCCACTAAGCTTGGTTCCATTGCAATTCAGGGAGCCATTGAAAAGGCAGGG
ATTCCAAAAGAAGAAGTGAAAGAAGCATACATGGGTAATGTTCTACAAGGAGGTGAAGGA
CAAGCTCCTACAAGGCAGGCAGTATTGGGTGCAGGCTTACCTATTTCTACTCCATGTACC
ACCATAAACAAAGTTTGTGCTTCAGGAATGAAAGCCATCATGATGGCCTCTCAAAGTCTT
ATGTGTGGACATCAGGATGTGATGGTGGCAGGTGGGATGGAGAGCATGTCCAATGTTCCA
TATGTAATGAACAGAGGATCAACACCATATGGTGGGGTAAAGCTTGAAGATTTGATTGTA
AAAGACGGGCTAACTGATGTCTACAATAAAATTCATATGGGCAGCTGTGCTGAGAATACA
GCAAAGAAGCTGAATATTGCACGAAATGAACAGGACGCTTATGCTATTAATTCTTATACC
AGAAGTAAAGCAGCATGGGAAGCTGGGAAATTTGGAAATGAAGTTATTCCTGTCACAGTT
ACAGTAAAAGGTCAACCAGATGTAGTGGTGAAAGAAGATGAAGAATATAAACGTGTTGAT
TTTAGCAAAGTTCCAAAGCTGAAGACAGTTTTCCAGAAAGAAAATGGCACAGTAACAGCT
GCCAATGCCAGTACACTGAATGATGGAGCAGCTGCTCTGGTTCTCATGACGGCAGATGCA
GCGAAGAGGCTCAATGTTACACCACTGGCAAGAATAGTAGCATTTGCTGACGCTGCTGTA
GAACCTATTGATTTTCCAATTGCTCCTGTATATGCTGCATCTATGGTTCTTAAAGATGTG
GGATTGAAAAAAGAAGATATTGCAATGTGGGAAGTAAATGAAGCCTTTAGTCTGGTTGTA
CTAGCAAACATTAAAATGTTGGAGATTGATCCCCAAAAAGTGAATATCAATGGAGGAGCT
GTTTCTCTGGGACATCCAATTGGGATGTCTGGAGCCAGGATTGTTGGTCATTTGACTCAT
GCCTTGAAGCAAGGAGAATACGGTCTTGCCAGTATTTGCAATGGAGGAGGAGGTGCTTCT
GCCATGCTAATTCAGAAGCTGTAG
Protein Properties
Number of Residues 427
Molecular Weight 45199.2
Theoretical pI 8.846
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Acetyl-CoA acetyltransferase, mitochondrial
MAVLAALLRSGARSRSPLLRRLVQEIRYVERSYVSKPTLKEVVIVSATRTPIGSFLGSLS
LLPATKLGSIAIQGAIEKAGIPKEEVKEAYMGNVLQGGEGQAPTRQAVLGAGLPISTPCT
TINKVCASGMKAIMMASQSLMCGHQDVMVAGGMESMSNVPYVMNRGSTPYGGVKLEDLIV
KDGLTDVYNKIHMGSCAENTAKKLNIARNEQDAYAINSYTRSKAAWEAGKFGNEVIPVTV
TVKGQPDVVVKEDEEYKRVDFSKVPKLKTVFQKENGTVTAANASTLNDGAAALVLMTADA
AKRLNVTPLARIVAFADAAVEPIDFPIAPVYAASMVLKDVGLKKEDIAMWEVNEAFSLVV
LANIKMLEIDPQKVNINGGAVSLGHPIGMSGARIVGHLTHALKQGEYGLASICNGGGGAS
AMLIQKL
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P24752
UniProtKB/Swiss-Prot Entry Name THIL_HUMAN
PDB IDs
GenBank Gene ID D90228
GeneCard ID ACAT1
GenAtlas ID ACAT1
HGNC ID HGNC:93
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Aboulaich N, Vainonen JP, Stralfors P, Vener AV: Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes. Biochem J. 2004 Oct 15;383(Pt 2):237-48. [PubMed:15242332 ]
  4. Fukao T, Yamaguchi S, Kano M, Orii T, Fujiki Y, Osumi T, Hashimoto T: Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency. J Clin Invest. 1990 Dec;86(6):2086-92. [PubMed:1979337 ]
  5. Kano M, Fukao T, Yamaguchi S, Orii T, Osumi T, Hashimoto T: Structure and expression of the human mitochondrial acetoacetyl-CoA thiolase-encoding gene. Gene. 1991 Dec 30;109(2):285-90. [PubMed:1684944 ]
  6. Haapalainen AM, Merilainen G, Pirila PL, Kondo N, Fukao T, Wierenga RK: Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. Biochemistry. 2007 Apr 10;46(14):4305-21. Epub 2007 Mar 20. [PubMed:17371050 ]
  7. Fukao T, Yamaguchi S, Orii T, Hashimoto T: Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. Hum Mutat. 1995;5(2):113-20. [PubMed:7749408 ]
  8. Fukao T, Yamaguchi S, Orii T, Schutgens RB, Osumi T, Hashimoto T: Identification of three mutant alleles of the gene for mitochondrial acetoacetyl-coenzyme A thiolase. A complete analysis of two generations of a family with 3-ketothiolase deficiency. J Clin Invest. 1992 Feb;89(2):474-9. [PubMed:1346617 ]
  9. Fukao T, Yamaguchi S, Tomatsu S, Orii T, Frauendienst-Egger G, Schrod L, Osumi T, Hashimoto T: Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency. Biochem Biophys Res Commun. 1991 Aug 30;179(1):124-9. [PubMed:1715688 ]
  10. Wakazono A, Fukao T, Yamaguchi S, Hori T, Orii T, Lambert M, Mitchell GA, Lee GW, Hashimoto T: Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients. Hum Mutat. 1995;5(1):34-42. [PubMed:7728148 ]
  11. Fukao T, Nakamura H, Song XQ, Nakamura K, Orii KE, Kohno Y, Kano M, Yamaguchi S, Hashimoto T, Orii T, Kondo N: Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency. Hum Mutat. 1998;12(4):245-54. [PubMed:9744475 ]