ID   THIL_HUMAN              Reviewed;         427 AA.
AC   P24752; B2R6H1; G3XAB4; Q96FG8;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 1.
DT   27-MAR-2024, entry version 232.
DE   RecName: Full=Acetyl-CoA acetyltransferase, mitochondrial;
DE            EC=2.3.1.9 {ECO:0000255|PROSITE-ProRule:PRU10020, ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475};
DE   AltName: Full=Acetoacetyl-CoA thiolase;
DE   AltName: Full=T2;
DE   Flags: Precursor;
GN   Name=ACAT1; Synonyms=ACAT, MAT;
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] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX   PubMed=1979337; DOI=10.1172/jci114946;
RA   Fukao T., Yamaguchi S., Kano M., Orii T., Fujiki Y., Osumi T.,
RA   Hashimoto T.;
RT   "Molecular cloning and sequence of the complementary DNA encoding human
RT   mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant
RT   enzymes in cultured fibroblasts from patients with 3-ketothiolase
RT   deficiency.";
RL   J. Clin. Invest. 86:2086-2092(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1684944; DOI=10.1016/0378-1119(91)90623-j;
RA   Kano M., Fukao T., Yamaguchi S., Orii T., Osumi T., Hashimoto T.;
RT   "Structure and expression of the human mitochondrial acetoacetyl-CoA
RT   thiolase-encoding gene.";
RL   Gene 109:285-290(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-5.
RC   TISSUE=Brain;
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 50-78 AND 312-338.
RC   TISSUE=Adipocyte;
RX   PubMed=15242332; DOI=10.1042/bj20040647;
RA   Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT   "Vectorial proteomics reveal targeting, phosphorylation and specific
RT   fragmentation of polymerase I and transcript release factor (PTRF) at the
RT   surface of caveolae in human adipocytes.";
RL   Biochem. J. 383:237-248(2004).
RN   [8]
RP   PROTEIN SEQUENCE OF 50-78 AND 231-243, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   TISSUE=Fetal brain cortex;
RA   Lubec G., Chen W.-Q., Sun Y.;
RL   Submitted (DEC-2008) to UniProtKB.
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [10]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-174; LYS-181; LYS-251 AND
RP   LYS-263, AND 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   [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   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   [13]
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   [14]
RP   X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 35-427 IN COMPLEX WITH COENZYME A
RP   AND POTASSIUM, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP   ACTIVITY REGULATION, SUBUNIT, AND ACTIVE SITE.
RX   PubMed=17371050; DOI=10.1021/bi6026192;
RA   Haapalainen A.M., Merilaeinen G., Pirilae P.L., Kondo N., Fukao T.,
RA   Wierenga R.K.;
RT   "Crystallographic and kinetic studies of human mitochondrial acetoacetyl-
RT   CoA thiolase: the importance of potassium and chloride ions for its
RT   structure and function.";
RL   Biochemistry 46:4305-4321(2007).
RN   [15]
RP   REVIEW ON 3KTD VARIANTS.
RX   PubMed=7749408; DOI=10.1002/humu.1380050203;
RA   Fukao T., Yamaguchi S., Orii T., Hashimoto T.;
RT   "Molecular basis of beta-ketothiolase deficiency: mutations and
RT   polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase
RT   gene.";
RL   Hum. Mutat. 5:113-120(1995).
RN   [16]
RP   VARIANT 3KTD ARG-183.
RX   PubMed=1346617; DOI=10.1172/jci115608;
RA   Fukao T., Yamaguchi S., Orii T., Schutgens R.B.H., Osumi T., Hashimoto T.;
RT   "Identification of three mutant alleles of the gene for mitochondrial
RT   acetoacetyl-coenzyme A thiolase. A complete analysis of two generations of
RT   a family with 3-ketothiolase deficiency.";
RL   J. Clin. Invest. 89:474-479(1992).
RN   [17]
RP   VARIANT 3KTD THR-380, CHARACTERIZATION OF VARIANT 3KTD THR-380, FUNCTION,
RP   CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=1715688; DOI=10.1016/0006-291x(91)91343-b;
RA   Fukao T., Yamaguchi S., Tomatsu S., Orii T., Frauendienst-Egger G.,
RA   Schrod L., Osumi T., Hashimoto T.;
RT   "Evidence for a structural mutation (347Ala to Thr) in a German family with
RT   3-ketothiolase deficiency.";
RL   Biochem. Biophys. Res. Commun. 179:124-129(1991).
RN   [18]
RP   VARIANTS 3KTD ASP-158; MET-297 AND PRO-301, CHARACTERIZATION OF VARIANTS
RP   3KTD ASP-158; MET-297 AND PRO-301, FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RX   PubMed=7728148; DOI=10.1002/humu.1380050105;
RA   Wakazono A., Fukao T., Yamaguchi S., Hori T., Orii T., Lambert M.,
RA   Mitchell G.A., Lee G.W., Hashimoto T.;
RT   "Molecular, biochemical, and clinical characterization of mitochondrial
RT   acetoacetyl-coenzyme A thiolase deficiency in two further patients.";
RL   Hum. Mutat. 5:34-42(1995).
RN   [19]
RP   VARIANTS 3KTD SER-93; THR-312 AND PRO-333, CHARACTERIZATION OF VARIANTS
RP   3KTD SER-93; THR-312 AND PRO-333, FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RX   PubMed=9744475;
RX   DOI=10.1002/(sici)1098-1004(1998)12:4<245::aid-humu5>3.0.co;2-e;
RA   Fukao T., Nakamura H., Song X.-Q., Nakamura K., Orii K.E., Kohno Y.,
RA   Kano M., Yamaguchi S., Hashimoto T., Orii T., Kondo N.;
RT   "Characterization of N93S, I312T, and A333P missense mutations in two
RT   Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency.";
RL   Hum. Mutat. 12:245-254(1998).
CC   -!- FUNCTION: This is one of the enzymes that catalyzes the last step of
CC       the mitochondrial beta-oxidation pathway, an aerobic process breaking
CC       down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148,
CC       PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic
CC       cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a
CC       fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688,
CC       PubMed:7728148, PubMed:9744475). The activity of the enzyme is
CC       reversible and it can also catalyze the condensation of two acetyl-CoA
CC       molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a
CC       major role in ketone body metabolism (PubMed:17371050, PubMed:1715688,
CC       PubMed:7728148, PubMed:9744475). {ECO:0000269|PubMed:1715688,
CC       ECO:0000269|PubMed:17371050, ECO:0000269|PubMed:7728148,
CC       ECO:0000269|PubMed:9744475}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036,
CC         ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.9;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10020,
CC         ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050,
CC         ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC         Evidence={ECO:0000269|PubMed:17371050};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038;
CC         Evidence={ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050,
CC         ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + propanoyl-CoA = 2-methyl-3-oxobutanoyl-CoA + CoA;
CC         Xref=Rhea:RHEA:30719, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:57335, ChEBI:CHEBI:57392;
CC         Evidence={ECO:0000269|PubMed:17371050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30720;
CC         Evidence={ECO:0000305|PubMed:17371050};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30721;
CC         Evidence={ECO:0000305|PubMed:17371050};
CC   -!- ACTIVITY REGULATION: Activated by potassium ions, but not sodium ions.
CC       {ECO:0000269|PubMed:17371050}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=4 uM for acetoacetyl-CoA (at 25 degrees Celsius in the presence of
CC         40 mM KCl) {ECO:0000269|PubMed:17371050};
CC         KM=8 uM for acetoacetyl-CoA (at 25 degrees Celsius in the presence of
CC         40 mM NaCl) {ECO:0000269|PubMed:17371050};
CC         KM=20 uM for CoA (at 25 degrees Celsius in the presence of 40 mM KCl)
CC         {ECO:0000269|PubMed:17371050};
CC         KM=66 uM for CoA (at 25 degrees Celsius in the presence of 40 mM
CC         NaCl) {ECO:0000269|PubMed:17371050};
CC         KM=8 uM for 2-methyl-3-oxobutanoyl-CoA (at 25 degrees Celsius in the
CC         presence of 40 mM KCl) {ECO:0000269|PubMed:17371050};
CC         KM=8 uM for 2-methyl-3-oxobutanoyl-CoA (at 25 degrees Celsius in the
CC         presence of 40 mM NaCl) {ECO:0000269|PubMed:17371050};
CC         KM=508 uM for acetyl-CoA (at 25 degrees Celsius in the presence of 40
CC         mM KCl) {ECO:0000269|PubMed:17371050};
CC         Note=kcat is 21 sec(-1) for the degradation of acetoacetyl-CoA (at 25
CC         degrees Celsius in the presence of 40 mM KCl) (PubMed:17371050). kcat
CC         is 8 sec(-1) for the degradation of acetoacetyl-CoA (at 25 degrees
CC         Celsius in the presence of 40 mM NaCl) (PubMed:17371050). kcat is 61
CC         sec(-1) for the degradation of 2-methylacetoacetyl-CoA (at 25 degrees
CC         Celsius in the presence of 40 mM KCl) (PubMed:17371050). kcat is 14
CC         sec(-1) for the degradation of 2-methylacetoacetyl-CoA (at 25 degrees
CC         Celsius in the presence of 40 mM NaCl) (PubMed:17371050). kcat is 3.5
CC         sec(-1) for the synthesis of acetoacetyl-CoA (at 25 degrees Celsius
CC         in the presence of 40 mM KCl) (PubMed:17371050).
CC         {ECO:0000269|PubMed:17371050};
CC   -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC       {ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:7728148,
CC       ECO:0000269|PubMed:9744475}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:17371050}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:1979337}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P24752-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P24752-2; Sequence=VSP_056844, VSP_056845;
CC   -!- PTM: Succinylation at Lys-268, adjacent to a coenzyme A binding site.
CC       Desuccinylated by SIRT5 (By similarity). {ECO:0000250}.
CC   -!- DISEASE: 3-ketothiolase deficiency (3KTD) [MIM:203750]: An autosomal
CC       recessive inborn error of isoleucine catabolism characterized by
CC       intermittent ketoacidotic attacks associated with unconsciousness. Some
CC       patients die during an attack or are mentally retarded. Urinary
CC       excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid,
CC       triglylglycine, butanone is increased. It seems likely that the
CC       severity of this disease correlates better with the environmental or
CC       acquired factors than with the ACAT1 genotype.
CC       {ECO:0000269|PubMed:1346617, ECO:0000269|PubMed:1715688,
CC       ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC       {ECO:0000305}.
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DR   EMBL; D90228; BAA14278.1; -; mRNA.
DR   EMBL; D10511; BAA01387.1; -; Genomic_DNA.
DR   EMBL; AK312574; BAG35468.1; -; mRNA.
DR   EMBL; AP002433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471065; EAW67104.1; -; Genomic_DNA.
DR   EMBL; CH471065; EAW67105.1; -; Genomic_DNA.
DR   EMBL; BC010942; AAH10942.1; -; mRNA.
DR   CCDS; CCDS8339.1; -. [P24752-1]
DR   PIR; JH0255; JH0255.
DR   RefSeq; NP_000010.1; NM_000019.3. [P24752-1]
DR   PDB; 2F2S; X-ray; 2.00 A; A/B/C/D=41-427.
DR   PDB; 2IB7; X-ray; 2.05 A; A/B/C/D=34-427.
DR   PDB; 2IB8; X-ray; 1.85 A; A/B/C/D=34-427.
DR   PDB; 2IB9; X-ray; 2.05 A; A/B/C/D=34-427.
DR   PDB; 2IBU; X-ray; 1.90 A; A/B/C/D=34-427.
DR   PDB; 2IBW; X-ray; 1.90 A; A/B/C/D=34-427.
DR   PDB; 2IBY; X-ray; 1.85 A; A/B/C/D=34-427.
DR   PDBsum; 2F2S; -.
DR   PDBsum; 2IB7; -.
DR   PDBsum; 2IB8; -.
DR   PDBsum; 2IB9; -.
DR   PDBsum; 2IBU; -.
DR   PDBsum; 2IBW; -.
DR   PDBsum; 2IBY; -.
DR   AlphaFoldDB; P24752; -.
DR   SMR; P24752; -.
DR   BioGRID; 106556; 225.
DR   IntAct; P24752; 35.
DR   MINT; P24752; -.
DR   STRING; 9606.ENSP00000265838; -.
DR   BindingDB; P24752; -.
DR   ChEMBL; CHEMBL2616; -.
DR   DrugBank; DB09061; Cannabidiol.
DR   DrugBank; DB14009; Medical Cannabis.
DR   DrugBank; DB14011; Nabiximols.
DR   DrugBank; DB00795; Sulfasalazine.
DR   DrugCentral; P24752; -.
DR   GuidetoPHARMACOLOGY; 2435; -.
DR   SwissLipids; SLP:000000701; -.
DR   GlyGen; P24752; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P24752; -.
DR   MetOSite; P24752; -.
DR   PhosphoSitePlus; P24752; -.
DR   SwissPalm; P24752; -.
DR   BioMuta; ACAT1; -.
DR   DMDM; 135755; -.
DR   REPRODUCTION-2DPAGE; IPI00030363; -.
DR   EPD; P24752; -.
DR   jPOST; P24752; -.
DR   MassIVE; P24752; -.
DR   MaxQB; P24752; -.
DR   PaxDb; 9606-ENSP00000265838; -.
DR   PeptideAtlas; P24752; -.
DR   ProteomicsDB; 33702; -.
DR   ProteomicsDB; 54224; -. [P24752-1]
DR   Pumba; P24752; -.
DR   TopDownProteomics; P24752-1; -. [P24752-1]
DR   Antibodypedia; 1354; 632 antibodies from 38 providers.
DR   DNASU; 38; -.
DR   Ensembl; ENST00000265838.9; ENSP00000265838.4; ENSG00000075239.14. [P24752-1]
DR   Ensembl; ENST00000299355.10; ENSP00000299355.6; ENSG00000075239.14. [P24752-2]
DR   GeneID; 38; -.
DR   KEGG; hsa:38; -.
DR   MANE-Select; ENST00000265838.9; ENSP00000265838.4; NM_000019.4; NP_000010.1.
DR   UCSC; uc001pjw.2; human. [P24752-1]
DR   AGR; HGNC:93; -.
DR   CTD; 38; -.
DR   DisGeNET; 38; -.
DR   GeneCards; ACAT1; -.
DR   HGNC; HGNC:93; ACAT1.
DR   HPA; ENSG00000075239; Tissue enhanced (kidney, liver).
DR   MalaCards; ACAT1; -.
DR   MIM; 203750; phenotype.
DR   MIM; 607809; gene.
DR   neXtProt; NX_P24752; -.
DR   OpenTargets; ENSG00000075239; -.
DR   Orphanet; 134; Beta-ketothiolase deficiency.
DR   PharmGKB; PA24431; -.
DR   VEuPathDB; HostDB:ENSG00000075239; -.
DR   eggNOG; KOG1390; Eukaryota.
DR   GeneTree; ENSGT01030000234626; -.
DR   HOGENOM; CLU_031026_0_1_1; -.
DR   InParanoid; P24752; -.
DR   OMA; SMGTFGE; -.
DR   OrthoDB; 5481312at2759; -.
DR   PhylomeDB; P24752; -.
DR   TreeFam; TF300650; -.
DR   BioCyc; MetaCyc:HS01167-MONOMER; -.
DR   PathwayCommons; P24752; -.
DR   Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR   Reactome; R-HSA-77108; Utilization of Ketone Bodies.
DR   Reactome; R-HSA-77111; Synthesis of Ketone Bodies.
DR   SABIO-RK; P24752; -.
DR   SignaLink; P24752; -.
DR   SIGNOR; P24752; -.
DR   UniPathway; UPA00659; -.
DR   BioGRID-ORCS; 38; 29 hits in 1176 CRISPR screens.
DR   ChiTaRS; ACAT1; human.
DR   EvolutionaryTrace; P24752; -.
DR   GeneWiki; ACAT1; -.
DR   GenomeRNAi; 38; -.
DR   Pharos; P24752; Tchem.
DR   PRO; PR:P24752; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P24752; Protein.
DR   Bgee; ENSG00000075239; Expressed in nephron tubule and 208 other cell types or tissues.
DR   ExpressionAtlas; P24752; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProt.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IDA:BHF-UCL.
DR   GO; GO:0016453; F:C-acetyltransferase activity; IDA:BHF-UCL.
DR   GO; GO:0034736; F:cholesterol O-acyltransferase activity; IDA:UniProt.
DR   GO; GO:0120225; F:coenzyme A binding; IEA:Ensembl.
DR   GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0030955; F:potassium ion binding; IDA:BHF-UCL.
DR   GO; GO:0006085; P:acetyl-CoA biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0046356; P:acetyl-CoA catabolic process; IDA:BHF-UCL.
DR   GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
DR   GO; GO:0015937; P:coenzyme A biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0015936; P:coenzyme A metabolic process; IDA:BHF-UCL.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR   GO; GO:0006550; P:isoleucine catabolic process; IMP:BHF-UCL.
DR   GO; GO:0046952; P:ketone body catabolic process; IMP:BHF-UCL.
DR   GO; GO:1902224; P:ketone body metabolic process; IC:BHF-UCL.
DR   GO; GO:0001889; P:liver development; IEA:Ensembl.
DR   GO; GO:0072229; P:metanephric proximal convoluted tubule development; IEA:Ensembl.
DR   GO; GO:1902860; P:propionyl-CoA biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR   CDD; cd00751; thiolase; 1.
DR   Gene3D; 3.40.47.10; -; 1.
DR   InterPro; IPR002155; Thiolase.
DR   InterPro; IPR016039; Thiolase-like.
DR   InterPro; IPR020615; Thiolase_acyl_enz_int_AS.
DR   InterPro; IPR020610; Thiolase_AS.
DR   InterPro; IPR020617; Thiolase_C.
DR   InterPro; IPR020613; Thiolase_CS.
DR   InterPro; IPR020616; Thiolase_N.
DR   NCBIfam; TIGR01930; AcCoA-C-Actrans; 1.
DR   PANTHER; PTHR18919:SF156; ACETYL-COA ACETYLTRANSFERASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR18919; ACETYL-COA C-ACYLTRANSFERASE; 1.
DR   Pfam; PF02803; Thiolase_C; 1.
DR   Pfam; PF00108; Thiolase_N; 1.
DR   PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR   SUPFAM; SSF53901; Thiolase-like; 2.
DR   PROSITE; PS00098; THIOLASE_1; 1.
DR   PROSITE; PS00737; THIOLASE_2; 1.
DR   PROSITE; PS00099; THIOLASE_3; 1.
DR   UCD-2DPAGE; P24752; -.
DR   Genevisible; P24752; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Acyltransferase; Alternative splicing;
KW   Direct protein sequencing; Disease variant; Fatty acid metabolism;
KW   Lipid metabolism; Metal-binding; Mitochondrion; Potassium;
KW   Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..33
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P17764"
FT   CHAIN           34..427
FT                   /note="Acetyl-CoA acetyltransferase, mitochondrial"
FT                   /id="PRO_0000034085"
FT   ACT_SITE        126
FT                   /note="Acyl-thioester intermediate"
FT                   /evidence="ECO:0000305|PubMed:17371050"
FT   ACT_SITE        413
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000305|PubMed:17371050"
FT   BINDING         219
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         219
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         258..260
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         263
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         280
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         281
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         283
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         284
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   BINDING         381
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000269|PubMed:17371050"
FT   SITE            385
FT                   /note="Increases nucleophilicity of active site Cys"
FT                   /evidence="ECO:0000305|PubMed:17371050"
FT   MOD_RES         66
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         66
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         78
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         174
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         174
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         181
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         181
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         190
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         190
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         202
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         202
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         223
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         223
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         230
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         230
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         243
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         251
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         257
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         263
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         263
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         266
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         268
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         273
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   MOD_RES         338
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT   VAR_SEQ         146..162
FT                   /note="DVMVAGGMESMSNVPYV -> IKQETGSLAKICCHVRR (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056844"
FT   VAR_SEQ         163..427
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056845"
FT   VARIANT         5
FT                   /note="A -> P (in dbSNP:rs3741056)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_007496"
FT   VARIANT         85
FT                   /note="Missing (in 3KTD)"
FT                   /id="VAR_007497"
FT   VARIANT         93
FT                   /note="N -> S (in 3KTD; decreased
FT                   acetyl-CoAC-acyltransferase activity; less than 10% of the
FT                   degradative/thiolase activity; dbSNP:rs120074145)"
FT                   /evidence="ECO:0000269|PubMed:9744475"
FT                   /id="VAR_007498"
FT   VARIANT         152
FT                   /note="G -> A (in 3KTD; dbSNP:rs762991875)"
FT                   /id="VAR_007499"
FT   VARIANT         158
FT                   /note="N -> D (in 3KTD; loss of acetyl-CoAC-acyltransferase
FT                   activity; no degradative/thiolase activity;
FT                   dbSNP:rs148639841)"
FT                   /evidence="ECO:0000269|PubMed:7728148"
FT                   /id="VAR_007500"
FT   VARIANT         183
FT                   /note="G -> R (in 3KTD; no activity; dbSNP:rs120074141)"
FT                   /evidence="ECO:0000269|PubMed:1346617"
FT                   /id="VAR_007501"
FT   VARIANT         297
FT                   /note="T -> M (in 3KTD; decreased protein abundance;
FT                   decreased acetyl-CoAC-acyltransferase activity; less than
FT                   10% of the degradative/thiolase activity;
FT                   dbSNP:rs886041122)"
FT                   /evidence="ECO:0000269|PubMed:7728148"
FT                   /id="VAR_007502"
FT   VARIANT         301
FT                   /note="A -> P (in 3KTD; loss of acetyl-CoAC-acyltransferase
FT                   activity; no degradative/thiolase activity;
FT                   dbSNP:rs1420321267)"
FT                   /evidence="ECO:0000269|PubMed:7728148"
FT                   /id="VAR_007503"
FT   VARIANT         312
FT                   /note="I -> T (in 3KTD; decreased protein stability;
FT                   decreased acetyl-CoAC-acyltransferase activity; less than
FT                   10% of the degradative/thiolase activity;
FT                   dbSNP:rs120074146)"
FT                   /evidence="ECO:0000269|PubMed:9744475"
FT                   /id="VAR_007504"
FT   VARIANT         333
FT                   /note="A -> P (in 3KTD; loss of protein solubility; loss of
FT                   acetyl-CoAC-acyltransferase activity; no
FT                   degradative/thiolase activity; dbSNP:rs120074147)"
FT                   /evidence="ECO:0000269|PubMed:9744475"
FT                   /id="VAR_007505"
FT   VARIANT         379
FT                   /note="G -> V (in 3KTD; dbSNP:rs120074143)"
FT                   /id="VAR_007506"
FT   VARIANT         380
FT                   /note="A -> T (in 3KTD; decreased protein stability;
FT                   dbSNP:rs120074140)"
FT                   /evidence="ECO:0000269|PubMed:1715688"
FT                   /id="VAR_007507"
FT   CONFLICT        340
FT                   /note="V -> M (in Ref. 2; BAA01387)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        346
FT                   /note="D -> N (in Ref. 2; BAA01387)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        380
FT                   /note="A -> S (in Ref. 2; BAA01387)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        412
FT                   /note="I -> F (in Ref. 2; BAA01387)"
FT                   /evidence="ECO:0000305"
FT   STRAND          42..49
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            58..61
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           64..79
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           83..85
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          88..92
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           103..110
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          119..123
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           125..127
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           128..141
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          146..155
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           156..158
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          161..163
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          165..167
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          173..177
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           178..182
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            187..190
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           193..204
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           208..227
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            228..234
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          238..240
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          248..250
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           255..257
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            261..263
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           264..266
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          273..275
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            280..282
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          287..297
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           298..303
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          310..319
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           322..327
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           328..340
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           344..346
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          347..352
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           357..367
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           371..373
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           380..383
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            387..389
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   HELIX           390..401
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          407..414
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   TURN            415..417
FT                   /evidence="ECO:0007829|PDB:2IB8"
FT   STRAND          418..426
FT                   /evidence="ECO:0007829|PDB:2IB8"
SQ   SEQUENCE   427 AA;  45200 MW;  2E81168EB39D0142 CRC64;
     MAVLAALLRS GARSRSPLLR RLVQEIRYVE RSYVSKPTLK EVVIVSATRT PIGSFLGSLS
     LLPATKLGSI AIQGAIEKAG IPKEEVKEAY MGNVLQGGEG QAPTRQAVLG AGLPISTPCT
     TINKVCASGM KAIMMASQSL MCGHQDVMVA GGMESMSNVP YVMNRGSTPY GGVKLEDLIV
     KDGLTDVYNK IHMGSCAENT AKKLNIARNE QDAYAINSYT RSKAAWEAGK FGNEVIPVTV
     TVKGQPDVVV KEDEEYKRVD FSKVPKLKTV FQKENGTVTA ANASTLNDGA AALVLMTADA
     AKRLNVTPLA RIVAFADAAV EPIDFPIAPV YAASMVLKDV GLKKEDIAMW EVNEAFSLVV
     LANIKMLEID PQKVNINGGA VSLGHPIGMS GARIVGHLTH ALKQGEYGLA SICNGGGGAS
     AMLIQKL
//