THIKB_RAT
ID THIKB_RAT Reviewed; 424 AA.
AC P07871; Q4G049;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=3-ketoacyl-CoA thiolase B, peroxisomal {ECO:0000305};
DE EC=2.3.1.155 {ECO:0000269|PubMed:10064897, ECO:0000269|PubMed:2882519};
DE EC=2.3.1.16 {ECO:0000269|PubMed:10064897, ECO:0000269|PubMed:2882519};
DE EC=2.3.1.9 {ECO:0000269|PubMed:10064897};
DE AltName: Full=Acetyl-CoA acyltransferase B;
DE AltName: Full=Beta-ketothiolase B;
DE AltName: Full=Peroxisomal 3-oxoacyl-CoA thiolase B;
DE Flags: Precursor;
GN Name=Acaa1b {ECO:0000312|RGD:1562373}; Synonyms=Acaa1;
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].
RX PubMed=3036803; DOI=10.1016/s0021-9258(18)47542-4;
RA Hijikata M., Ishii N., Kagamiyama H., Osumi T., Hashimoto T.;
RT "Structural analysis of cDNA for rat peroxisomal 3-ketoacyl-CoA thiolase.";
RL J. Biol. Chem. 262:8151-8158(1987).
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].
RC TISSUE=Liver;
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 FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=2882519; DOI=10.1073/pnas.84.8.2494;
RA Schram A.W., Goldfischer S., van Roermund C.W., Brouwer-Kelder E.M.,
RA Collins J., Hashimoto T., Heymans H.S., van den Bosch H., Schutgens R.B.,
RA Tager J.M.;
RT "Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2494-2496(1987).
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).
RN [6]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=10064897; DOI=10.1016/s1388-1981(99)00003-7;
RA Antonenkov V.D., Van Veldhoven P.P., Waelkens E., Mannaerts G.P.;
RT "Comparison of the stability and substrate specificity of purified
RT peroxisomal 3-oxoacyl-CoA thiolases A and B from rat liver.";
RL Biochim. Biophys. Acta 1437:136-141(1999).
CC -!- FUNCTION: Responsible for the thiolytic cleavage of straight chain 3-
CC keto fatty acyl-CoAs (3-oxoacyl-CoAs) (PubMed:10064897,
CC PubMed:2882519). Plays an important role in fatty acid peroxisomal
CC beta-oxidation (PubMed:10064897, PubMed:2882519). Catalyzes the
CC cleavage of short, medium, long, and very long straight chain 3-
CC oxoacyl-CoAs (PubMed:10064897, PubMed:2882519). Medium chain straight
CC 3-oxoacyl-CoAs are preferred substrates (PubMed:10064897).
CC {ECO:0000269|PubMed:10064897, ECO:0000269|PubMed:2882519}.
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:10064897, ECO:0000269|PubMed:2882519};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566;
CC Evidence={ECO:0000269|PubMed:2882519, ECO:0000305|PubMed:10064897};
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:10064897};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038;
CC Evidence={ECO:0000305|PubMed:10064897};
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:10064897};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31205;
CC Evidence={ECO:0000305|PubMed:10064897};
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:10064897, ECO:0000269|PubMed:2882519};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18163;
CC Evidence={ECO:0000269|PubMed:2882519, ECO:0000305|PubMed:10064897};
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:10064897};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40344;
CC Evidence={ECO:0000305|PubMed:10064897};
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=7.0 uM for acetoacetyl-CoA {ECO:0000269|PubMed:10064897};
CC KM=8.2 uM for 3-oxooctanoyl-CoA {ECO:0000269|PubMed:10064897};
CC KM=6.7 uM for 3-oxohexadecanoyl-CoA {ECO:0000269|PubMed:10064897};
CC KM=3.2 uM for 3-oxohexadecanedioyl-CoA {ECO:0000269|PubMed:10064897};
CC Vmax=24.4 umol/min/mg enzyme for the degradation of acetoacetyl-CoA
CC {ECO:0000269|PubMed:10064897};
CC Vmax=141.8 umol/min/mg enzyme for the degradation of 3-oxooctanoyl-
CC CoA {ECO:0000269|PubMed:10064897};
CC Vmax=15.6 umol/min/mg enzyme for the degradation of 3-
CC oxohexadecanoyl-CoA {ECO:0000269|PubMed:10064897};
CC Vmax=120.3 umol/min/mg enzyme for the degradation of 3-
CC oxohexadecanedioyl-CoA {ECO:0000269|PubMed:10064897};
CC -!- PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:10064897, ECO:0000269|PubMed:2882519}.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:10064897}.
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 -!- MISCELLANEOUS: There exist at least 2 rat liver peroxisomal 3-ketoacyl-
CC CoA thiolases.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; J02749; AAA41497.1; -; mRNA.
DR EMBL; D90063; BAA14107.1; -; Genomic_DNA.
DR EMBL; BC098757; AAH98757.1; -; mRNA.
DR PIR; B35725; XURTAB.
DR RefSeq; NP_001035108.1; NM_001040019.1.
DR AlphaFoldDB; P07871; -.
DR SMR; P07871; -.
DR IntAct; P07871; 1.
DR SwissLipids; SLP:000001213; -.
DR iPTMnet; P07871; -.
DR PhosphoSitePlus; P07871; -.
DR jPOST; P07871; -.
DR PRIDE; P07871; -.
DR Ensembl; ENSRNOT00000106186; ENSRNOP00000086036; ENSRNOG00000067803.
DR GeneID; 501072; -.
DR KEGG; rno:501072; -.
DR UCSC; RGD:1562373; rat.
DR CTD; 235674; -.
DR RGD; 1562373; Acaa1b.
DR GeneTree; ENSGT01030000234626; -.
DR InParanoid; P07871; -.
DR OrthoDB; 1011220at2759; -.
DR PhylomeDB; P07871; -.
DR Reactome; R-RNO-2046106; alpha-linolenic acid (ALA) metabolism.
DR Reactome; R-RNO-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR SABIO-RK; P07871; -.
DR UniPathway; UPA00661; -.
DR PRO; PR:P07871; -.
DR Proteomes; UP000002494; Chromosome 8.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0050633; F:acetyl-CoA C-myristoyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
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 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; Fatty acid metabolism; Lipid metabolism;
KW Peroxisome; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..26
FT /note="Peroxisome"
FT /evidence="ECO:0000269|PubMed:1680677"
FT CHAIN 27..424
FT /note="3-ketoacyl-CoA thiolase B, peroxisomal"
FT /id="PRO_0000034071"
FT ACT_SITE 123
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT ACT_SITE 408
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT BINDING 249
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT BINDING 252
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT BINDING 276
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT SITE 377
FT /note="Increases nucleophilicity of active site Cys"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCH0"
FT MOD_RES 234
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q921H8"
FT CONFLICT 44
FT /note="R -> Q (in Ref. 1; AAA41497)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="L -> P (in Ref. 1; AAA41497)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="L -> V (in Ref. 2; BAA14107)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 424 AA; 43820 MW; E1D41A3C65477D77 CRC64;
MHRLQVVLGH LAGRSESSSA LQAAPCSAGF PQASASDVVV VHGRRTPIGR AGRGGFKDTT
PDELLSAVLT AVLQDVKLKP ECLGDISVGN VLQPGAGAAM ARIAQFLSGI PETVPLSAVN
RQCSSGLQAV ANIAGGIRNG SYDIGMACGV ESMTLSERGN PGNISSRLLE NEKARDCLIP
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
