ID   THIKA_RAT               Reviewed;         434 AA.
AC   P21775; Q5FVR9;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2021, sequence version 3.
DT   08-NOV-2023, entry version 153.
DE   RecName: Full=3-ketoacyl-CoA thiolase A, peroxisomal {ECO:0000305};
DE            EC=2.3.1.16 {ECO:0000269|PubMed:9325339};
DE   AltName: Full=Acetyl-CoA C-myristoyltransferase;
DE            EC=2.3.1.155 {ECO:0000269|PubMed:9325339};
DE   AltName: Full=Acetyl-CoA acyltransferase A;
DE            EC=2.3.1.9 {ECO:0000269|PubMed:9325339};
DE   AltName: Full=Beta-ketothiolase A;
DE   AltName: Full=Peroxisomal 3-oxoacyl-CoA thiolase A;
DE   AltName: Full=Thiolase A {ECO:0000303|PubMed:9325339};
DE   Flags: Precursor;
GN   Name=Acaa1a {ECO:0000312|RGD:67379};
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] (ISOFORM 1), INDUCTION, AND SUBCELLULAR
RP   LOCATION.
RC   STRAIN=Sprague-Dawley;
RX   PubMed=2210380; DOI=10.1016/0378-1119(90)90088-9;
RA   Bodnar A.G., Rachubinski R.A.;
RT   "Cloning and sequence determination of cDNA encoding a second rat liver
RT   peroxisomal 3-ketoacyl-CoA thiolase.";
RL   Gene 91:193-199(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Sprague-Dawley;
RX   PubMed=2307679; DOI=10.1016/s0021-9258(19)39605-x;
RA   Hijikata M., Wen J.K., Osumi T., Hashimoto T.;
RT   "Rat peroxisomal 3-ketoacyl-CoA thiolase gene. Occurrence of two closely
RT   related but differentially regulated genes.";
RL   J. Biol. Chem. 265:4600-4606(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PROTEIN SEQUENCE OF 40-57, CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR
RP   LOCATION, PATHWAY, AND TISSUE SPECIFICITY.
RX   PubMed=9325339; DOI=10.1074/jbc.272.41.26023;
RA   Antonenkov V.D., Van Veldhoven P.P., Waelkens E., Mannaerts G.P.;
RT   "Substrate specificities of 3-oxoacyl-CoA thiolase A and sterol carrier
RT   protein 2/3-oxoacyl-CoA thiolase purified from normal rat liver
RT   peroxisomes. Sterol carrier protein 2/3-oxoacyl-CoA thiolase is involved in
RT   the metabolism of 2-methyl-branched fatty acids and bile acid
RT   intermediates.";
RL   J. Biol. Chem. 272:26023-26031(1997).
RN   [5]
RP   TRANSIT PEPTIDE CLEAVAGE SITE, AND DOMAIN.
RX   PubMed=1680677; DOI=10.1002/j.1460-2075.1991.tb04889.x;
RA   Swinkels B.W., Gould S.J., Bodnar A.G., Rachubinski R.A., Subramani S.;
RT   "A novel, cleavable peroxisomal targeting signal at the amino-terminus of
RT   the rat 3-ketoacyl-CoA thiolase.";
RL   EMBO J. 10:3255-3262(1991).
CC   -!- FUNCTION: Responsible for the thiolytic cleavage of straight chain 3-
CC       keto fatty acyl-CoAs (3-oxoacyl-CoAs) (PubMed:9325339). Plays an
CC       important role in fatty acid peroxisomal beta-oxidation
CC       (PubMed:9325339). Catalyzes the cleavage of short, medium, long, and
CC       very long straight chain 3-oxoacyl-CoAs (PubMed:9325339). Medium chain
CC       straight 3-oxoacyl-CoAs are preferred substrates (PubMed:9325339).
CC       {ECO:0000269|PubMed:9325339}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + an acyl-CoA = a 3-oxoacyl-CoA + CoA;
CC         Xref=Rhea:RHEA:21564, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:58342, ChEBI:CHEBI:90726; EC=2.3.1.16;
CC         Evidence={ECO:0000269|PubMed:9325339};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566;
CC         Evidence={ECO:0000305|PubMed:9325339};
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:0000269|PubMed:9325339};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038;
CC         Evidence={ECO:0000305|PubMed:9325339};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA + CoA;
CC         Xref=Rhea:RHEA:18161, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:57349, ChEBI:CHEBI:57385; EC=2.3.1.155;
CC         Evidence={ECO:0000269|PubMed:9325339};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18163;
CC         Evidence={ECO:0000305|PubMed:9325339};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + hexanoyl-CoA = 3-oxooctanoyl-CoA + CoA;
CC         Xref=Rhea:RHEA:31203, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:62619, ChEBI:CHEBI:62620;
CC         Evidence={ECO:0000269|PubMed:9325339};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31205;
CC         Evidence={ECO:0000305|PubMed:9325339};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-oxohexadecanedioyl-CoA + CoA = acetyl-CoA +
CC         tetradecanedioyl-CoA; Xref=Rhea:RHEA:40343, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57288, ChEBI:CHEBI:77081, ChEBI:CHEBI:77084;
CC         Evidence={ECO:0000269|PubMed:9325339};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40344;
CC         Evidence={ECO:0000305|PubMed:9325339};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-oxo-(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + CoA =
CC         (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + acetyl-CoA;
CC         Xref=Rhea:RHEA:39131, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:74298, ChEBI:CHEBI:74304;
CC         Evidence={ECO:0000250|UniProtKB:P09110};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39132;
CC         Evidence={ECO:0000250|UniProtKB:P09110};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=7.7 uM for acetoacetyl-CoA {ECO:0000269|PubMed:9325339};
CC         KM=9.1 uM for 3-oxooctanoyl-CoA {ECO:0000269|PubMed:9325339};
CC         KM=7.8 uM for 3-oxohexadecanoyl-CoA {ECO:0000269|PubMed:9325339};
CC         KM=3.4 uM for 3-oxohexadecanedioyl-CoA {ECO:0000269|PubMed:9325339};
CC         Vmax=26.8 umol/min/mg enzyme towards acetoacetyl-CoA
CC         {ECO:0000269|PubMed:9325339};
CC         Vmax=145 umol/min/mg enzyme towards 3-oxooctanoyl-CoA
CC         {ECO:0000269|PubMed:9325339};
CC         Vmax=14.3 umol/min/mg enzyme towards 3-oxohexadecanoyl-CoA
CC         {ECO:0000269|PubMed:9325339};
CC         Vmax=128 umol/min/mg enzyme towards 3-oxohexadecanedioyl-CoA
CC         {ECO:0000269|PubMed:9325339};
CC       pH dependence:
CC         Optimum pH is 8 with acetoacetyl-CoA and 3-oxooctanoyl-CoA as
CC         substrates. {ECO:0000269|PubMed:9325339};
CC   -!- PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation.
CC       {ECO:0000269|PubMed:9325339}.
CC   -!- SUBUNIT: Homodimer. Interacts (via PTS2-type peroxisomal targeting
CC       signal region) with PEX7; leading to its translocation into
CC       peroxisomes. {ECO:0000250|UniProtKB:P09110}.
CC   -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:1680677,
CC       ECO:0000269|PubMed:2210380, ECO:0000269|PubMed:9325339}.
CC       Note=Transported into peroxisomes following association with PEX7.
CC       {ECO:0000250|UniProtKB:P09110}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P21775-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P21775-2; Sequence=VSP_023746;
CC   -!- INDUCTION: Peroxisomal thiolase is markedly induced (at the level of
CC       transcription) by various hypolipidemic compounds in parallel with the
CC       other two enzymes of the peroxisomal beta-oxidation system.
CC       {ECO:0000269|PubMed:2210380}.
CC   -!- DOMAIN: The PTS2-type peroxisomal targeting signal, which mediates
CC       interaction with PEX7 and localization to peroxisomes, is cleaved
CC       following import into peroxisomes. {ECO:0000269|PubMed:1680677}.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC       {ECO:0000305}.
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DR   EMBL; M32801; AAA41471.1; -; mRNA.
DR   EMBL; D90058; BAA14106.1; -; Genomic_DNA.
DR   EMBL; BC089821; AAH89821.1; -; mRNA.
DR   PIR; A35725; XURTAA.
DR   RefSeq; NP_036621.1; NM_012489.2.
DR   AlphaFoldDB; P21775; -.
DR   SMR; P21775; -.
DR   STRING; 10116.ENSRNOP00000050691; -.
DR   PhosphoSitePlus; P21775; -.
DR   jPOST; P21775; -.
DR   PaxDb; 10116-ENSRNOP00000050691; -.
DR   PeptideAtlas; P21775; -.
DR   GeneID; 24157; -.
DR   KEGG; rno:24157; -.
DR   AGR; RGD:67379; -.
DR   CTD; 113868; -.
DR   RGD; 67379; Acaa1a.
DR   eggNOG; KOG1389; Eukaryota.
DR   InParanoid; P21775; -.
DR   OrthoDB; 5481312at2759; -.
DR   PhylomeDB; P21775; -.
DR   SABIO-RK; P21775; -.
DR   UniPathway; UPA00661; -.
DR   PRO; PR:P21775; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR   GO; GO:0008775; F:acetate CoA-transferase activity; ISO:RGD.
DR   GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0050633; F:acetyl-CoA C-myristoyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0016401; F:palmitoyl-CoA oxidase activity; IGI:UniProtKB.
DR   GO; GO:0008206; P:bile acid metabolic process; IDA:UniProtKB.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR   GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; IEA:UniProtKB-UniPathway.
DR   GO; GO:0010124; P:phenylacetate catabolic process; IBA:GO_Central.
DR   GO; GO:0007584; P:response to nutrient; IDA:RGD.
DR   GO; GO:0048545; P:response to steroid hormone; IDA:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0000038; P:very long-chain fatty acid metabolic process; ISO: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; PTHR43853:SF19; 3-KETOACYL-COA THIOLASE A, PEROXISOMAL; 1.
DR   PANTHER; PTHR43853; 3-KETOACYL-COA THIOLASE, PEROXISOMAL; 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.
PE   1: Evidence at protein level;
KW   Acetylation; Acyltransferase; Alternative splicing;
KW   Direct protein sequencing; Fatty acid metabolism; Lipid metabolism;
KW   Peroxisome; Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..36
FT                   /note="Peroxisome"
FT                   /evidence="ECO:0000269|PubMed:1680677"
FT   CHAIN           37..434
FT                   /note="3-ketoacyl-CoA thiolase A, peroxisomal"
FT                   /id="PRO_0000034070"
FT   REGION          11..36
FT                   /note="PTS2-type peroxisomal targeting signal"
FT                   /evidence="ECO:0000269|PubMed:1680677"
FT   ACT_SITE        133
FT                   /note="Acyl-thioester intermediate"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        387
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT   ACT_SITE        418
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT   MOD_RES         183
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q921H8"
FT   MOD_RES         244
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q921H8"
FT   VAR_SEQ         344..434
FT                   /note="LTVNDIDIFEINEAFASQALYCVEKLGIPAEKVNPLGGAIALGHPLGCTGAR
FT                   QVVTLLNELKRRGRRAYGVVSMCIGTGMGAAAVFEYPGN -> PLLCGEAGNSCREGEP
FT                   PGGCNSPGPPPGLHRSKAGGHAAQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_023746"
FT   CONFLICT        39
FT                   /note="T -> S (in Ref. 3; AAH89821)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        245
FT                   /note="G -> S (in Ref. 3; AAH89821)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        409
FT                   /note="R -> T (in Ref. 1; AAA41471)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   434 AA;  44839 MW;  85189FB6D294E135 CRC64;
     MSESVGRTSA MHRLQVVLGH LAGRPESSSA LQAAPCSATF PQASASDVVV VHGRRTPIGR
     AGRGGFKDTT PDELLSAVLT AVLQDVKLKP ECLGDISVGN VLEPGAGAVM ARIAQFLSGI
     PETVPLSAVN RQCSSGLQAV ANIAGGIRNG SYDIGMACGV ESMSLSNRGN PGNISSRLLE
     SDKARDCLIP MGITSENVAE RFGISRQKQD AFALASQQKA ASAQSKGCFR AEIVPVTTTV
     LDDKGDRKTI TVSQDEGVRP STTMEGLAKL KPAFKDGGST TAGNSSQVSD GAAAVLLARR
     SKAEELGLPI LGVLRSYAVV GVPPDIMGIG PAYAIPAALQ KAGLTVNDID IFEINEAFAS
     QALYCVEKLG IPAEKVNPLG GAIALGHPLG CTGARQVVTL LNELKRRGRR AYGVVSMCIG
     TGMGAAAVFE YPGN
//