THIL_RAT
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 03-AUG-2022, entry version 173.
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 iPTMnet; P17764; -.
DR PhosphoSitePlus; P17764; -.
DR jPOST; P17764; -.
DR PaxDb; P17764; -.
DR PRIDE; P17764; -.
DR Ensembl; ENSRNOT00000010573; ENSRNOP00000010573; ENSRNOG00000007862.
DR GeneID; 25014; -.
DR KEGG; rno:25014; -.
DR UCSC; RGD:2016; rat.
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; TNVCCTT; -.
DR OrthoDB; 1011220at2759; -.
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 tissues.
DR Genevisible; P17764; RN.
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: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:0007420; P:brain 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 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 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
