THIM_PONAB
ID THIM_PONAB Reviewed; 397 AA.
AC Q5RES5;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=3-ketoacyl-CoA thiolase, mitochondrial {ECO:0000305};
DE EC=2.3.1.16 {ECO:0000250|UniProtKB:P42765};
DE AltName: Full=Acetyl-CoA acetyltransferase {ECO:0000305};
DE EC=2.3.1.9 {ECO:0000255|PROSITE-ProRule:PRU10020};
DE AltName: Full=Acetyl-CoA acyltransferase;
DE AltName: Full=Acyl-CoA hydrolase, mitochondrial {ECO:0000305};
DE EC=3.1.2.- {ECO:0000250|UniProtKB:P42765};
DE EC=3.1.2.1 {ECO:0000250|UniProtKB:P42765};
DE EC=3.1.2.2 {ECO:0000250|UniProtKB:P13437};
DE AltName: Full=Beta-ketothiolase;
DE AltName: Full=Mitochondrial 3-oxoacyl-CoA thiolase;
GN Name=ACAA2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. Using free coenzyme A/CoA, catalyzes the thiolytic cleavage
CC of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and
CC a fatty acyl-CoA shortened by two carbon atoms. Also catalyzes the
CC condensation of two acetyl-CoA molecules into acetoacetyl-CoA and could
CC be involved in the production of ketone bodies. Also displays hydrolase
CC activity on various fatty acyl-CoAs (By similarity). Thereby, could be
CC responsible for the production of acetate in a side reaction to beta-
CC oxidation (By similarity). Abolishes BNIP3-mediated apoptosis and
CC mitochondrial damage (By similarity). {ECO:0000250|UniProtKB:P13437,
CC ECO:0000250|UniProtKB:P42765}.
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:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21565;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:P42765};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21038;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20290;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40104;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40112;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40116;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:0000250|UniProtKB:P42765};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000250|UniProtKB:P42765};
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:0000250|UniProtKB:P13437};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000250|UniProtKB:P42765};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:P42765}.
CC -!- SUBUNIT: Homotetramer. Interacts with BNIP3.
CC {ECO:0000250|UniProtKB:P42765}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P42765}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR857441; CAH89732.1; -; mRNA.
DR RefSeq; NP_001124791.1; NM_001131319.1.
DR AlphaFoldDB; Q5RES5; -.
DR SMR; Q5RES5; -.
DR PRIDE; Q5RES5; -.
DR GeneID; 100171644; -.
DR KEGG; pon:100171644; -.
DR CTD; 10449; -.
DR InParanoid; Q5RES5; -.
DR OrthoDB; 1129049at2759; -.
DR UniPathway; UPA00659; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003986; F:acetyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; ISS: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:0006635; P:fatty acid beta-oxidation; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript 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_0000270499"
FT TRANSIT 1..16
FT /note="Mitochondrion; not cleaved"
FT /evidence="ECO:0000250"
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:0000250|UniProtKB:P42765"
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 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42765"
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 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 234
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
FT MOD_RES 234
FT /note="N6-succinyllysine; alternate"
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 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWT1"
SQ SEQUENCE 397 AA; 41907 MW; 5AFC50C22C39F82D CRC64;
MALLRGVFVV AAKRTPFGAY GGLLKDFTAT DLSEFAAKAA LSAGKVSPET VDSVIMGNVL
QSSSDAIYLA RHVGLRVGIP KETPALTINR LCGSGFQSIV NGCQEICVKE AEVVLCGGTE
SMSQAPYCVR TVRFGTKLGS DIKLEDSLWV SLTDQHVQLP IAMTAENLAV KHKISREECD
KYALQSQQRW KAANDAGYFN DEMAPIEVKT KKGKQTMQVD EHARPQTTLE QLQKLPPVFK
KDGTVTAGNA SGIADGAGAV IIASEDAVKK HNFTPLARIV GYFVSGCDPS IMGIGPVPAI
SGALKKAGLS LKDMDLVEVN EAFAPQYLAV ERSLDLDISK TNVNGGAIAL GHPLGGSGSR
ITAHLVHELR RRGGKYAVGS ACIGGGQGIA VIIQSTA
