THIKA_RAT
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 03-AUG-2022, entry version 148.
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.
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.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:2210380,
CC ECO:0000269|PubMed:9325339}.
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 -!- 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 iPTMnet; P21775; -.
DR PhosphoSitePlus; P21775; -.
DR jPOST; P21775; -.
DR PeptideAtlas; P21775; -.
DR PRIDE; P21775; -.
DR GeneID; 24157; -.
DR KEGG; rno:24157; -.
DR CTD; 113868; -.
DR RGD; 67379; Acaa1a.
DR eggNOG; KOG1389; Eukaryota.
DR InParanoid; P21775; -.
DR OrthoDB; 1129049at2759; -.
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 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; 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 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
