THIL_HUMAN
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 03-AUG-2022, entry version 223.
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; 197.
DR IntAct; P24752; 30.
DR MINT; P24752; -.
DR STRING; 9606.ENSP00000265838; -.
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 UCD-2DPAGE; P24752; -.
DR EPD; P24752; -.
DR jPOST; P24752; -.
DR MassIVE; P24752; -.
DR MaxQB; P24752; -.
DR PaxDb; P24752; -.
DR PeptideAtlas; P24752; -.
DR PRIDE; P24752; -.
DR ProteomicsDB; 33702; -.
DR ProteomicsDB; 54224; -. [P24752-1]
DR TopDownProteomics; P24752-1; -. [P24752-1]
DR Antibodypedia; 1354; 586 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 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; TNVCCTT; -.
DR PhylomeDB; P24752; -.
DR TreeFam; TF300650; -.
DR BioCyc; MetaCyc:HS01167-MON; -.
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; 27 hits in 1095 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 206 other tissues.
DR ExpressionAtlas; P24752; baseline and differential.
DR Genevisible; P24752; HS.
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:UniProtKB.
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: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:0007420; P:brain 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 Pfam; PF02803; Thiolase_C; 1.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1.
DR PROSITE; PS00098; THIOLASE_1; 1.
DR PROSITE; PS00737; THIOLASE_2; 1.
DR PROSITE; PS00099; THIOLASE_3; 1.
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 acetyl-CoA C-
FT acyltransferase activity; less than 10% of the degradative/
FT 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-CoA C-
FT acyltransferase 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-CoA C-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-CoA C-
FT acyltransferase 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-CoA C-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-CoA C-acyltransferase activity; no degradative/
FT 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
