THIL_DANRE
ID THIL_DANRE Reviewed; 420 AA.
AC Q6AZA0;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 113.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (AUG-2004) 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 -!- 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 -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; BC078651; AAH78651.1; -; mRNA.
DR RefSeq; NP_001003746.1; NM_001003746.1.
DR AlphaFoldDB; Q6AZA0; -.
DR SMR; Q6AZA0; -.
DR STRING; 7955.ENSDARP00000067447; -.
DR PaxDb; Q6AZA0; -.
DR PeptideAtlas; Q6AZA0; -.
DR PRIDE; Q6AZA0; -.
DR Ensembl; ENSDART00000170182; ENSDARP00000133230; ENSDARG00000045888.
DR GeneID; 445290; -.
DR KEGG; dre:445290; -.
DR CTD; 38; -.
DR ZFIN; ZDB-GENE-040808-68; acat1.
DR eggNOG; KOG1390; Eukaryota.
DR GeneTree; ENSGT01030000234626; -.
DR HOGENOM; CLU_031026_0_1_1; -.
DR InParanoid; Q6AZA0; -.
DR OrthoDB; 797770at2759; -.
DR PhylomeDB; Q6AZA0; -.
DR TreeFam; TF300650; -.
DR Reactome; R-DRE-70895; Branched-chain amino acid catabolism.
DR Reactome; R-DRE-77108; Utilization of Ketone Bodies.
DR Reactome; R-DRE-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00659; -.
DR PRO; PR:Q6AZA0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 10.
DR Bgee; ENSDARG00000045888; Expressed in cardiac ventricle and 27 other tissues.
DR ExpressionAtlas; Q6AZA0; baseline and differential.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
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 Acyltransferase; Fatty acid metabolism; Lipid metabolism; Metal-binding;
KW Mitochondrion; Potassium; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P17764"
FT CHAIN 27..420
FT /note="Acetyl-CoA acetyltransferase, mitochondrial"
FT /id="PRO_0000356275"
FT ACT_SITE 119
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 406
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 212
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 212
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 251..253
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 256
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 273
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 274
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 277
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 374
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT SITE 378
FT /note="Increases nucleophilicity of active site Cys"
FT /evidence="ECO:0000250|UniProtKB:P24752"
SQ SEQUENCE 420 AA; 44342 MW; 9A9323F4C36674C4 CRC64;
MTSRALYSTR SQLCRHLAHK YLSRSYSTRP SLNEVVIVSA VRTPIGSFKG SLSTLPATKL
GSIAIKGAID KAGIPVEEVK EVYMGNVLQA GEGQAPTRQA LLGAGLPLST PATTINKVCA
SGMKSIMLAS QSLMCGHQDV MVAGGMESMS QVPYIMAREA PPYGGVKMED LIVKDGLTDV
YNKFHMGNCA ENTAKNSSIS REEQDAFAIK SYTLSKAAWE SGILAKEVVP VSIPQRGKPD
VVVKEDEEYR KVDFSKVPKL KAVFLKENGT VTAANASTLN DGAAALVLMT ADAAQRLNVT
PLAKIVAFAD AAVAPIDFPI APAFAVPKVL KAAGIKKEDI AMWEINEAFS VVVLANIKML
DIDPDRVNIN GGAVSLGHPI GMSGARIVGH MVHNLKSGQY GLAGICNGGG GASSIVIQKF
