THIL_BOVIN
ID THIL_BOVIN Reviewed; 422 AA.
AC Q29RZ0;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 112.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
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-263, 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}.
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DR EMBL; BC113328; AAI13329.1; -; mRNA.
DR RefSeq; NP_001039540.1; NM_001046075.1.
DR AlphaFoldDB; Q29RZ0; -.
DR SMR; Q29RZ0; -.
DR IntAct; Q29RZ0; 1.
DR STRING; 9913.ENSBTAP00000017122; -.
DR PaxDb; Q29RZ0; -.
DR PeptideAtlas; Q29RZ0; -.
DR PRIDE; Q29RZ0; -.
DR Ensembl; ENSBTAT00000017122; ENSBTAP00000017122; ENSBTAG00000012885.
DR GeneID; 511082; -.
DR KEGG; bta:511082; -.
DR CTD; 38; -.
DR VEuPathDB; HostDB:ENSBTAG00000012885; -.
DR VGNC; VGNC:25529; ACAT1.
DR eggNOG; KOG1390; Eukaryota.
DR GeneTree; ENSGT01030000234626; -.
DR HOGENOM; CLU_031026_0_1_1; -.
DR InParanoid; Q29RZ0; -.
DR OMA; TNVCCTT; -.
DR OrthoDB; 1011220at2759; -.
DR TreeFam; TF300650; -.
DR Reactome; R-BTA-70895; Branched-chain amino acid catabolism.
DR Reactome; R-BTA-77108; Utilization of Ketone Bodies.
DR Reactome; R-BTA-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00659; -.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000012885; Expressed in metanephros cortex and 107 other tissues.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0030955; F:potassium ion binding; IEA:Ensembl.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IEA:Ensembl.
DR GO; GO:0046356; P:acetyl-CoA catabolic process; IEA:Ensembl.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IEA:Ensembl.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR GO; GO:0006550; P:isoleucine catabolic process; IEA:Ensembl.
DR GO; GO:0046952; P:ketone body catabolic process; IEA:Ensembl.
DR GO; GO:1902860; P:propionyl-CoA biosynthetic process; 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 2: Evidence at transcript level;
KW Acetylation; Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Metal-binding; Mitochondrion; Potassium; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P17764"
FT CHAIN 29..422
FT /note="Acetyl-CoA acetyltransferase, mitochondrial"
FT /id="PRO_0000356274"
FT ACT_SITE 121
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 408
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 214
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 214
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 253..255
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 258
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 275
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 276
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 279
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 376
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT SITE 380
FT /note="Increases nucleophilicity of active site Cys"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT MOD_RES 61
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 61
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 73
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 169
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT MOD_RES 169
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 176
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT MOD_RES 176
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 185
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 185
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 197
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 197
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 218
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 218
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 238
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 240
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 240
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 246
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 258
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT MOD_RES 258
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 261
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 263
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
FT MOD_RES 333
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZT1"
SQ SEQUENCE 422 AA; 44889 MW; 17B8975F0DB3FE9D CRC64;
MPVLAALLRR GPLLQRRVQE IRYAERSYVS KPTLNEVVIV SAIRTPIGSF LGSLSSLPAT
KLGSIAIQGA IEKAGIPKEE VKEAYMGNVL QGGEGQAPTR QAVLGAGLPI STPCTTINKV
CASGMKAIMM ASQNLMCGHQ DVMVAGGMES MSNVPYVMNR GATPYGGVKL EDLIVKDGLT
DVYNKIHMGN CAENTAKKLN ITREEQDTYA LNSYTRSKAA WEAGRFGNEV VPVTITVKGK
PDVVVKEDEE YKRVDFSKIP KLKTVFQREN GTVTAANAST LNDGAAAVVL MTADAAKRLN
VKPLARIAAF ADAAVEPIDF PLAPAYAVPK VLKDAGLKKE DITMWEVNEA FSVVVLANIK
MLEMDPQKVN INGGAVSLGH PIGMSGARIV VHLAHALKQG EYGLASICNG GGGASAMLIQ
KL
