THIM_RAT
ID THIM_RAT Reviewed; 397 AA.
AC P13437;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=3-ketoacyl-CoA thiolase, mitochondrial {ECO:0000305};
DE EC=2.3.1.16 {ECO:0000269|PubMed:16476568};
DE AltName: Full=Acetyl-CoA acetyltransferase {ECO:0000305};
DE EC=2.3.1.9 {ECO:0000269|PubMed:16476568};
DE AltName: Full=Acetyl-CoA acyltransferase;
DE AltName: Full=Acyl-CoA hydrolase, mitochondrial {ECO:0000305};
DE EC=3.1.2.- {ECO:0000269|PubMed:16476568};
DE EC=3.1.2.1 {ECO:0000269|PubMed:16476568};
DE EC=3.1.2.2 {ECO:0000269|PubMed:16476568};
DE AltName: Full=Beta-ketothiolase;
DE AltName: Full=Mitochondrial 3-oxoacyl-CoA thiolase;
GN Name=Acaa2;
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].
RC TISSUE=Liver;
RX PubMed=3038520; DOI=10.1002/j.1460-2075.1987.tb02376.x;
RA Arakawa H., Takiguchi M., Amaya Y., Nagata S., Hayashi H., Mori M.;
RT "cDNA-derived amino acid sequence of rat mitochondrial 3-oxoacyl-CoA
RT thiolase with no transient presequence: structural relationship with
RT peroxisomal isozyme.";
RL EMBO J. 6:1361-1366(1987).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION BY DEHP.
RX PubMed=16476568; DOI=10.1016/j.bbalip.2006.01.001;
RA Yamashita H., Itsuki A., Kimoto M., Hiemori M., Tsuji H.;
RT "Acetate generation in rat liver mitochondria; acetyl-CoA hydrolase
RT activity is demonstrated by 3-ketoacyl-CoA thiolase.";
RL Biochim. Biophys. Acta 1761:17-23(2006).
CC -!- FUNCTION: In the production of energy from fats, this is one of the
CC enzymes that catalyzes the last step of the mitochondrial beta-
CC oxidation pathway, an aerobic process breaking down fatty acids into
CC acetyl-CoA (Probable). Using free coenzyme A/CoA, catalyzes the
CC thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs
CC into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms
CC (Probable). Also catalyzes the condensation of two acetyl-CoA molecules
CC into acetoacetyl-CoA and could be involved in the production of ketone
CC bodies (Probable). Also displays hydrolase activity on various fatty
CC acyl-CoAs (PubMed:16476568). Thereby, could be responsible for the
CC production of acetate in a side reaction to beta-oxidation (Probable).
CC Abolishes BNIP3-mediated apoptosis and mitochondrial damage (By
CC similarity). {ECO:0000250|UniProtKB:P42765,
CC ECO:0000269|PubMed:16476568, ECO:0000305|PubMed:16476568}.
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:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21565;
CC Evidence={ECO:0000305|PubMed:16476568};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566;
CC Evidence={ECO:0000305|PubMed:16476568};
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:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC Evidence={ECO:0000305|PubMed:16476568};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + H2O = acetate + CoA + H(+); Xref=Rhea:RHEA:20289,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=3.1.2.1;
CC Evidence={ECO:0000269|PubMed:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20290;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + propanoyl-CoA = CoA + H(+) + propanoate;
CC Xref=Rhea:RHEA:40103, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17272, ChEBI:CHEBI:57287, ChEBI:CHEBI:57392;
CC Evidence={ECO:0000269|PubMed:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40104;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoyl-CoA + H2O = butanoate + CoA + H(+);
CC Xref=Rhea:RHEA:40111, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17968, ChEBI:CHEBI:57287, ChEBI:CHEBI:57371;
CC Evidence={ECO:0000269|PubMed:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40112;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexanoyl-CoA = CoA + H(+) + hexanoate;
CC Xref=Rhea:RHEA:40115, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17120, ChEBI:CHEBI:57287, ChEBI:CHEBI:62620;
CC Evidence={ECO:0000269|PubMed:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40116;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + octanoyl-CoA = CoA + H(+) + octanoate;
CC Xref=Rhea:RHEA:30143, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:25646, ChEBI:CHEBI:57287, ChEBI:CHEBI:57386;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30144;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + H2O = CoA + decanoate + H(+);
CC Xref=Rhea:RHEA:40059, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:27689, ChEBI:CHEBI:57287, ChEBI:CHEBI:61430;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H2O = CoA + dodecanoate + H(+);
CC Xref=Rhea:RHEA:30135, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:57287, ChEBI:CHEBI:57375;
CC Evidence={ECO:0000269|PubMed:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + tetradecanoyl-CoA = CoA + H(+) + tetradecanoate;
CC Xref=Rhea:RHEA:40119, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57287, ChEBI:CHEBI:57385;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoyl-CoA = CoA + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:16645, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379; EC=3.1.2.2;
CC Evidence={ECO:0000269|PubMed:16476568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:16476568};
CC -!- ACTIVITY REGULATION: The 3-oxoacetyl-CoA thiolase activity is inhibited
CC by acetyl-CoA while the acetyl-CoA hydrolase activity is inhibited by
CC acetoacetyl-CoA. {ECO:0000269|PubMed:16476568}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11.4 uM for acetoacetyl-CoA {ECO:0000269|PubMed:16476568};
CC KM=0.71 mM for acetyl-CoA {ECO:0000269|PubMed:16476568};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:16476568}.
CC -!- SUBUNIT: Homotetramer. Interacts with BNIP3 (By similarity).
CC {ECO:0000250|UniProtKB:P42765}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16476568}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, brown adipose tissue and heart
CC (at protein level). {ECO:0000269|PubMed:16476568}.
CC -!- INDUCTION: Up-regulated in liver, brown adipose tissue, heart,
CC intestine and kidney by DEHP/bis(2-ethylhexyl)phthalate (at protein
CC level). {ECO:0000269|PubMed:16476568}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; X05341; CAA28952.1; -; mRNA.
DR PIR; A29452; XURT.
DR RefSeq; NP_569117.1; NM_130433.1.
DR AlphaFoldDB; P13437; -.
DR SMR; P13437; -.
DR BioGRID; 250910; 3.
DR IntAct; P13437; 2.
DR STRING; 10116.ENSRNOP00000060140; -.
DR SwissLipids; SLP:000001412; -.
DR CarbonylDB; P13437; -.
DR iPTMnet; P13437; -.
DR PhosphoSitePlus; P13437; -.
DR jPOST; P13437; -.
DR PaxDb; P13437; -.
DR PRIDE; P13437; -.
DR GeneID; 170465; -.
DR KEGG; rno:170465; -.
DR CTD; 10449; -.
DR RGD; 620482; Acaa2.
DR eggNOG; KOG1391; Eukaryota.
DR InParanoid; P13437; -.
DR OrthoDB; 1129049at2759; -.
DR PhylomeDB; P13437; -.
DR Reactome; R-RNO-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR SABIO-RK; P13437; -.
DR UniPathway; UPA00659; -.
DR PRO; PR:P13437; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; ISO:RGD.
DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; IDA:RGD.
DR GO; GO:0003986; F:acetyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; IDA:UniProtKB.
DR GO; GO:0102991; F:myristoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IDA:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:RGD.
DR GO; GO:1902109; P:negative regulation of mitochondrial membrane permeability involved in apoptotic process; ISO:RGD.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
DR CDD; cd00751; thiolase; 1.
DR Gene3D; 3.40.47.10; -; 2.
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; Hydrolase;
KW Lipid metabolism; Mitochondrion; Phosphoprotein; Reference proteome;
KW Transferase; Transit peptide.
FT CHAIN 1..397
FT /note="3-ketoacyl-CoA thiolase, mitochondrial"
FT /id="PRO_0000223301"
FT TRANSIT 1..16
FT /note="Mitochondrion; not cleaved"
FT ACT_SITE 92
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT ACT_SITE 382
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT BINDING 224
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT BINDING 227
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT BINDING 251
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT SITE 352
FT /note="Increases nucleophilicity of active site Cys"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT MOD_RES 25
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 25
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 45
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 119
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT MOD_RES 127
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT MOD_RES 136
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 137
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 137
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 143
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 143
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 158
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 158
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 171
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 171
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 191
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 191
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 209
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 209
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 211
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 212
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 214
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 240
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 269
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 270
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 305
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 305
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 312
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 312
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42765"
FT MOD_RES 340
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
SQ SEQUENCE 397 AA; 41871 MW; 8344FB7271C3E2E1 CRC64;
MALLRGVFIV AAKRTPFGAY GGLLKDFTAT DLTEFAARAA LSAGKVPPET IDSVIVGNVM
QSSSDAAYLA RHVGLRVGVP TETGALTLNR LCGSGFQSIV SGCQEICSKD AEVVLCGGTE
SMSQSPYSVR NVRFGTKFGL DLKLEDTLWA GLTDQHVKLP MGMTAENLAA KYNISREDCD
RYALQSQQRW KAANEAGYFN EEMAPIEVKT KKGKQTMQVD EHARPQTTLE QLQNLPPVFK
KEGTVTAGNA SGMSDGAGVV IIASEDAVKK HNFTPLARVV GYFVSGCDPA IMGIGPVPAI
TGALKKAGLS LKDMDLIDVN EAFAPQFLAV QKSLDLDPSK TNVSGGAIAL GHPLGGSGSR
ITAHLVHELR RRGGKYAVGS ACIGGGQGIS LIIQNTA
