ID THIL_RAT Reviewed; 424 AA. AC P17764; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=Acetyl-CoA acetyltransferase, mitochondrial; DE EC=2.3.1.9 {ECO:0000250|UniProtKB:P24752}; DE AltName: Full=Acetoacetyl-CoA thiolase; DE Flags: Precursor; GN Name=Acat1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 31-50. RX PubMed=2478525; DOI=10.1093/oxfordjournals.jbchem.a122832; RA Fukao T., Kamijo K., Osumi T., Fujiki Y., Yamaguchi S., Orii T., RA Hashimoto T.; RT "Molecular cloning and nucleotide sequence of cDNA encoding the entire RT precursor of rat mitochondrial acetoacetyl-CoA thiolase."; RL J. Biochem. 106:197-204(1989). 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. Using free coenzyme A/CoA, catalyzes CC the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into CC acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms. The CC activity of the enzyme is reversible and it can also catalyze the CC condensation of two acetyl-CoA molecules into acetoacetyl-CoA. Thereby, CC it plays a major role in ketone body metabolism. CC {ECO:0000250|UniProtKB:P24752}. 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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037; CC Evidence={ECO:0000250|UniProtKB:P24752}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038; CC Evidence={ECO:0000250|UniProtKB:P24752}; 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:0000250|UniProtKB:P24752}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30720; CC Evidence={ECO:0000250|UniProtKB:P24752}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30721; CC Evidence={ECO:0000250|UniProtKB:P24752}; CC -!- ACTIVITY REGULATION: Activated by potassium ions, but not sodium ions. CC {ECO:0000250|UniProtKB:P24752}. CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation. CC {ECO:0000250|UniProtKB:P24752}. CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P24752}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P24752}. CC -!- PTM: Succinylation at Lys-265, adjacent to a coenzyme A binding site. CC Desuccinylated by SIRT5 (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D00512; BAA00401.1; ALT_SEQ; mRNA. DR EMBL; D13921; BAA03016.1; -; mRNA. DR PIR; JU0072; XXRTAC. DR RefSeq; NP_058771.2; NM_017075.2. DR AlphaFoldDB; P17764; -. DR SMR; P17764; -. DR BioGRID; 247097; 1. DR IntAct; P17764; 3. DR MINT; P17764; -. DR STRING; 10116.ENSRNOP00000010573; -. DR BindingDB; P17764; -. DR ChEMBL; CHEMBL3393; -. DR GuidetoPHARMACOLOGY; 2435; -. DR CarbonylDB; P17764; -. DR GlyGen; P17764; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P17764; -. DR PhosphoSitePlus; P17764; -. DR SwissPalm; P17764; -. DR jPOST; P17764; -. DR PaxDb; 10116-ENSRNOP00000010573; -. DR Ensembl; ENSRNOT00000010573.6; ENSRNOP00000010573.3; ENSRNOG00000007862.7. DR Ensembl; ENSRNOT00055047965; ENSRNOP00055039493; ENSRNOG00055027672. DR Ensembl; ENSRNOT00060028059; ENSRNOP00060022580; ENSRNOG00060016362. DR Ensembl; ENSRNOT00065029319; ENSRNOP00065023265; ENSRNOG00065017528. DR GeneID; 25014; -. DR KEGG; rno:25014; -. DR UCSC; RGD:2016; rat. DR AGR; RGD:2016; -. DR CTD; 38; -. DR RGD; 2016; Acat1. DR eggNOG; KOG1390; Eukaryota. DR GeneTree; ENSGT01030000234626; -. DR HOGENOM; CLU_031026_0_1_1; -. DR InParanoid; P17764; -. DR OMA; SMGTFGE; -. DR OrthoDB; 5481312at2759; -. DR PhylomeDB; P17764; -. DR TreeFam; TF300650; -. DR Reactome; R-RNO-70895; Branched-chain amino acid catabolism. DR Reactome; R-RNO-77108; Utilization of Ketone Bodies. DR Reactome; R-RNO-77111; Synthesis of Ketone Bodies. DR SABIO-RK; P17764; -. DR UniPathway; UPA00659; -. DR PRO; PR:P17764; -. DR Proteomes; UP000002494; Chromosome 8. DR Bgee; ENSRNOG00000007862; Expressed in heart and 19 other cell types or tissues. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD. DR GO; GO:0005759; C:mitochondrial matrix; IDA:RGD. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IDA:RGD. DR GO; GO:0016453; F:C-acetyltransferase activity; ISO:RGD. DR GO; GO:0034736; F:cholesterol O-acyltransferase activity; ISO:RGD. DR GO; GO:0120225; F:coenzyme A binding; IPI:RGD. DR GO; GO:0019899; F:enzyme binding; IPI:RGD. DR GO; GO:0042802; F:identical protein binding; IPI:RGD. DR GO; GO:0030955; F:potassium ion binding; ISO:RGD. DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; ISO:RGD. DR GO; GO:0046356; P:acetyl-CoA catabolic process; ISO:RGD. DR GO; GO:0060612; P:adipose tissue development; IEP:RGD. DR GO; GO:0015937; P:coenzyme A biosynthetic process; ISO:RGD. DR GO; GO:0015936; P:coenzyme A metabolic process; ISO:RGD. DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central. DR GO; GO:0006550; P:isoleucine catabolic process; ISO:RGD. DR GO; GO:0046952; P:ketone body catabolic process; ISO:RGD. DR GO; GO:0001889; P:liver development; IEP:RGD. DR GO; GO:0072229; P:metanephric proximal convoluted tubule development; IEP:RGD. DR GO; GO:1902860; P:propionyl-CoA biosynthetic process; ISO:RGD. DR GO; GO:0009725; P:response to hormone; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0042594; P:response to starvation; IEP:RGD. 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 Genevisible; P17764; RN. PE 1: Evidence at protein level; KW Acetylation; Acyltransferase; Direct protein sequencing; KW Fatty acid metabolism; Lipid metabolism; Metal-binding; Mitochondrion; KW Phosphoprotein; Potassium; Reference proteome; Transferase; KW Transit peptide. FT TRANSIT 1..30 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:2478525" FT CHAIN 31..424 FT /note="Acetyl-CoA acetyltransferase, mitochondrial" FT /id="PRO_0000034088" FT ACT_SITE 123 FT /note="Acyl-thioester intermediate" FT /evidence="ECO:0000250|UniProtKB:P24752" FT ACT_SITE 410 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 216 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 216 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 255..257 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 260 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 277 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 278 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 280 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 281 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250|UniProtKB:P24752" FT BINDING 378 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:P24752" FT SITE 382 FT /note="Increases nucleophilicity of active site Cys" FT /evidence="ECO:0000250|UniProtKB:P24752" FT MOD_RES 63 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 63 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 75 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 171 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P24752" FT MOD_RES 171 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 178 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P24752" FT MOD_RES 178 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 187 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 187 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 199 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 199 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 204 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 220 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 220 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 227 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 227 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 240 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 242 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 242 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 248 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P24752" FT MOD_RES 254 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 260 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P24752" FT MOD_RES 260 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 263 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 265 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 270 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" FT MOD_RES 335 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8QZT1" SQ SEQUENCE 424 AA; 44695 MW; 79E8881DB242EFEE CRC64; MAALAVLHGV VRRPLLRGLL QEVRCLGRSY ASKPTLNDVV IVSATRTPIG SFLGSLASQP ATKLGTIAIQ GAIEKAGIPK EEVKEVYMGN VIQGGEGQAP TRQATLGAGL PIATPCTTVN KVCASGMKAI MMASQSLMCG HQDVMVAGGM ESMSNVPYVM SRGATPYGGV KLEDLIVKDG LTDVYNKIHM GNCAENTAKK LSISREEQDK YAIGSYTRSK EAWDAGKFAN EITPITISVK GKPDVVVKED EEYKRVDFSK VPKLKTVFQK ENGTVTAANA STLNDGAAAV VLMTAEAAQR LKVKPLARIA AFADAAVDPI DFPLAPAYAV PKVLKYAGLK KEDIAMWEVN EAFSVVVLAN IKMLEIDPQK VNVHGGAVSL GHPIGMSGAR IVVHLAHALK QGEFGLASIC NGGGGASAVL IEKL //