THIL_MACFA
ID THIL_MACFA Reviewed; 427 AA.
AC Q8HXY6;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 87.
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; ORFNames=QtrA-14294;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Temporal cortex;
RA Kusuda J., Osada N., Hida M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (APR-2002) 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-268, 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; AB083303; BAC20582.1; -; mRNA.
DR RefSeq; NP_001270524.1; NM_001283595.1.
DR AlphaFoldDB; Q8HXY6; -.
DR SMR; Q8HXY6; -.
DR STRING; 9541.XP_005579588.1; -.
DR GeneID; 102134087; -.
DR CTD; 38; -.
DR eggNOG; KOG1390; Eukaryota.
DR OrthoDB; 1011220at2759; -.
DR UniPathway; UPA00659; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:UniProtKB-UniPathway.
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..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P17764"
FT CHAIN 34..427
FT /note="Acetyl-CoA acetyltransferase, mitochondrial"
FT /id="PRO_0000034086"
FT ACT_SITE 126
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 413
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 219
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 219
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 258..260
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 263
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
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="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 283
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 284
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 381
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT SITE 385
FT /note="Increases nucleophilicity of active site Cys"
FT /evidence="ECO:0000250|UniProtKB:P24752"
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:0000250|UniProtKB:P24752"
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:0000250|UniProtKB:P24752"
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:0000250|UniProtKB:P24752"
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:0000250|UniProtKB:P24752"
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"
SQ SEQUENCE 427 AA; 45200 MW; D44BEC44A38AF478 CRC64;
MAVLAALLRG GARSRSPLLR RLVQEIRYVE RSYVSKPTLK EVVIVSATRT PIGSFLGSLS
LLPTTKLGSI AMQGAIEKAG IPKEEVKEAY MGNVLQGGEG QAPARQAVLG AGLPISTPRT
TINKVCASGM KAIMMASQSL MCGHQDVMVA GGMESMSNVP YVMNRGSTPY GGVKLEDLIV
KDGLTDVYNK IHMGSCAENT AKKLNIARDE QDAYAINSYT RSKAAWEAGK FGNEVIPVTV
TVKGQPDVVV KEDEEYKRVD FSKVPKLKTV FQKENGTITA ANASTLNDGA AALVLMTAGA
AKRLNVTPLA RIVAFADAAV EPIDFPIAPV HAVSMVLKDV GLKKEDIAMW EVNEAFSLVV
LANIKMLEID PQKVNINGGA VSLGHPIGMS GARIVGHLTH ALKQGEYGLA SICNGGGGAS
AMLIQKL
