ACOT1_MOUSE
ID ACOT1_MOUSE Reviewed; 419 AA.
AC O55137; Q549A9;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Acyl-coenzyme A thioesterase 1 {ECO:0000250|UniProtKB:Q86TX2};
DE Short=Acyl-CoA thioesterase 1 {ECO:0000250|UniProtKB:Q86TX2};
DE EC=3.1.2.- {ECO:0000250|UniProtKB:Q86TX2};
DE AltName: Full=CTE-I;
DE AltName: Full=Inducible cytosolic acyl-coenzyme A thioester hydrolase;
DE AltName: Full=Long chain acyl-CoA thioester hydrolase;
DE Short=Long chain acyl-CoA hydrolase;
DE AltName: Full=Palmitoyl-coenzyme A thioesterase {ECO:0000250|UniProtKB:Q86TX2};
DE EC=3.1.2.2 {ECO:0000250|UniProtKB:Q86TX2};
GN Name=Acot1; Synonyms=Cte1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=10567408; DOI=10.1074/jbc.274.48.34317;
RA Hunt M.C., Nousiainen S.E.B., Huttunen M.K., Orii K.E., Svensson L.T.,
RA Alexson S.E.H.;
RT "Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise
RT a highly conserved novel multi-gene family involved in lipid metabolism.";
RL J. Biol. Chem. 274:34317-34326(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11330065; DOI=10.1385/cbb:32:1-3:317;
RA Hunt M.C., Lindquist P.J.G., Nousiainen S.E.B., Huttunen M.K., Orii K.E.,
RA Svensson L.T., Aoyama T., Hashimoto T., Diczfalusy U., Alexson S.E.H.;
RT "Acyl-CoA thioesterases belong to a novel gene family of peroxisome
RT proliferator-regulated enzymes involved in lipid metabolism.";
RL Cell Biochem. Biophys. 32:317-324(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=9490035; DOI=10.1046/j.1432-1327.1998.2510631.x;
RA Lindquist P.J.G., Svensson L.T., Alexson S.E.H.;
RT "Molecular cloning of the peroxisome proliferator-induced 46-kDa cytosolic
RT acyl-CoA thioesterase from mouse and rat liver --recombinant expression in
RT Escherichia coli, tissue expression, and nutritional regulation.";
RL Eur. J. Biochem. 251:631-640(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, ACTIVE SITES, AND MUTAGENESIS OF SER-232; ASP-324 AND
RP HIS-358.
RX PubMed=11694534; DOI=10.1074/jbc.m109040200;
RA Huhtinen K., O'Byrne J., Lindquist P.J.G., Contreras J.A., Alexson S.E.H.;
RT "The peroxisome proliferator-induced cytosolic type I acyl-CoA thioesterase
RT (CTE-I) is a serine-histidine-aspartic acid alpha /beta hydrolase.";
RL J. Biol. Chem. 277:3424-3432(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids
CC and coenzyme A (CoASH), regulating their respective intracellular
CC levels. More active towards saturated and unsaturated long chain fatty
CC acyl-CoAs (C12-C20). {ECO:0000269|PubMed:11694534}.
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:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:11694534};
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:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000305|PubMed:11694534};
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:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000305|PubMed:11694534};
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:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000305|PubMed:11694534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + octadecanoyl-CoA = CoA + H(+) + octadecanoate;
CC Xref=Rhea:RHEA:30139, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394;
CC Evidence={ECO:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30140;
CC Evidence={ECO:0000305|PubMed:11694534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + H2O = CoA + eicosanoate + H(+);
CC Xref=Rhea:RHEA:40147, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32360, ChEBI:CHEBI:57287, ChEBI:CHEBI:57380;
CC Evidence={ECO:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40148;
CC Evidence={ECO:0000305|PubMed:11694534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+);
CC Xref=Rhea:RHEA:40139, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387;
CC Evidence={ECO:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000305|PubMed:11694534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-hexadecenoyl-CoA + H2O = (9Z)-hexadecenoate + CoA + H(+);
CC Xref=Rhea:RHEA:40131, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32372, ChEBI:CHEBI:57287, ChEBI:CHEBI:61540;
CC Evidence={ECO:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40132;
CC Evidence={ECO:0000305|PubMed:11694534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9E)-octadecenoyl-CoA + H2O = (9E)-octadecenoate + CoA + H(+);
CC Xref=Rhea:RHEA:40723, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30825, ChEBI:CHEBI:57287, ChEBI:CHEBI:77537;
CC Evidence={ECO:0000269|PubMed:11694534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40724;
CC Evidence={ECO:0000305|PubMed:11694534};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.6 uM for C16:0-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=15.2 uM for C10:0-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=2.6 uM for C12:0-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=3.5 uM for C14:0-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=0.5 uM for C20:0-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=1.5 uM for C14:1-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=1.1 uM for C16:1-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=2.4 uM for C18:1(cis)-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=1.8 uM for C18:1(trans)-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=4.5 uM for C18:2-acyl-CoA {ECO:0000269|PubMed:11694534};
CC KM=3.0 uM for C20:4-acyl-CoA {ECO:0000269|PubMed:11694534};
CC Vmax=1.2 umol/min/mg enzyme with C16:0-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.192 umol/min/mg enzyme with C10:0-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.780 umol/min/mg enzyme with C12:0-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=1.68 umol/min/mg enzyme with C14:0-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.692 umol/min/mg enzyme with C18:0-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.245 umol/min/mg enzyme with C20:0-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.745 umol/min/mg enzyme with C14:1-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.621 umol/min/mg enzyme with C16:1-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.176 umol/min/mg enzyme with C18:1(cis)-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.188 umol/min/mg enzyme with C18:1(trans)-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.316 umol/min/mg enzyme with C18:2-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC Vmax=0.007 umol/min/mg enzyme with C20:4-acyl-CoA as substrate
CC {ECO:0000269|PubMed:11694534};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000305|PubMed:11694534}.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O88267}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, kidney, brown adipose tissue,
CC white adipose tissue, adrenal gland and muscle.
CC {ECO:0000269|PubMed:10567408, ECO:0000269|PubMed:11330065}.
CC -!- INDUCTION: In the liver, by peroxisome proliferator (Clofibrate)
CC treatment, via the peroxisome proliferator-activated receptors (PPARs)
CC or fasting for 24 hours. {ECO:0000269|PubMed:11330065}.
CC -!- SIMILARITY: Belongs to the C/M/P thioester hydrolase family.
CC {ECO:0000305}.
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DR EMBL; AF180795; AAF13870.1; -; Genomic_DNA.
DR EMBL; AF180793; AAF13870.1; JOINED; Genomic_DNA.
DR EMBL; AF180794; AAF13870.1; JOINED; Genomic_DNA.
DR EMBL; Y14004; CAA74327.1; -; mRNA.
DR EMBL; BC028261; AAH28261.1; -; mRNA.
DR CCDS; CCDS36487.1; -.
DR RefSeq; NP_036136.1; NM_012006.2.
DR AlphaFoldDB; O55137; -.
DR SMR; O55137; -.
DR STRING; 10090.ENSMUSP00000126448; -.
DR ChEMBL; CHEMBL3259489; -.
DR ESTHER; mouse-acot1; Acyl-CoA_Thioesterase.
DR MEROPS; S09.A52; -.
DR iPTMnet; O55137; -.
DR PhosphoSitePlus; O55137; -.
DR UCD-2DPAGE; O55137; -.
DR jPOST; O55137; -.
DR MaxQB; O55137; -.
DR PaxDb; O55137; -.
DR PeptideAtlas; O55137; -.
DR PRIDE; O55137; -.
DR ProteomicsDB; 285647; -.
DR DNASU; 26897; -.
DR Ensembl; ENSMUST00000168120; ENSMUSP00000126448; ENSMUSG00000072949.
DR GeneID; 26897; -.
DR KEGG; mmu:26897; -.
DR UCSC; uc007oeb.1; mouse.
DR CTD; 641371; -.
DR MGI; MGI:1349396; Acot1.
DR VEuPathDB; HostDB:ENSMUSG00000072949; -.
DR eggNOG; ENOG502QQ8Z; Eukaryota.
DR GeneTree; ENSGT01010000222336; -.
DR HOGENOM; CLU_029849_4_0_1; -.
DR InParanoid; O55137; -.
DR OMA; NTFMNEM; -.
DR OrthoDB; 1260385at2759; -.
DR PhylomeDB; O55137; -.
DR TreeFam; TF314911; -.
DR BRENDA; 3.1.2.2; 3474.
DR Reactome; R-MMU-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR SABIO-RK; O55137; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 26897; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Acot1; mouse.
DR PRO; PR:O55137; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; O55137; protein.
DR Bgee; ENSMUSG00000072949; Expressed in epithelium of small intestine and 270 other tissues.
DR ExpressionAtlas; O55137; baseline and differential.
DR Genevisible; O55137; MM.
DR GO; GO:0005737; C:cytoplasm; TAS:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; IDA:MGI.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IEA:UniProtKB-KW.
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:0006637; P:acyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:MGI.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR Gene3D; 2.60.40.2240; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR016662; Acyl-CoA_thioEstase_long-chain.
DR InterPro; IPR014940; BAAT_C.
DR InterPro; IPR006862; Thio_Ohase/aa_AcTrfase.
DR InterPro; IPR042490; Thio_Ohase/BAAT_N.
DR Pfam; PF08840; BAAT_C; 1.
DR Pfam; PF04775; Bile_Hydr_Trans; 1.
DR PIRSF; PIRSF016521; Acyl-CoA_hydro; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Fatty acid metabolism; Hydrolase; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Serine esterase.
FT CHAIN 1..419
FT /note="Acyl-coenzyme A thioesterase 1"
FT /id="PRO_0000202156"
FT ACT_SITE 232
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:11694534"
FT ACT_SITE 324
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:11694534"
FT ACT_SITE 358
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:11694534"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88267"
FT MUTAGEN 232
FT /note="S->A: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:11694534"
FT MUTAGEN 232
FT /note="S->C: Retains 2% of the initial activity;
FT deacylation of the acyl-enzyme intermediate becomes rate-
FT limiting."
FT /evidence="ECO:0000269|PubMed:11694534"
FT MUTAGEN 324
FT /note="D->A: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:11694534"
FT MUTAGEN 358
FT /note="H->Q: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:11694534"
SQ SEQUENCE 419 AA; 46136 MW; 57346B6177471CFB CRC64;
MEATLNLEPS GRSCWDEPLS IAVRGLAPEQ PVTLRSVLRD EKGALFRAHA RYRADSHGEL
DLARTPALGG SFSGLEPMGL LWAMEPDRPF WRLVKRDVQT PFVVELEVLD GHEPDGGQRL
AHAVHERHFL APGVRRVPVR EGRVRATLFL PPEPGPFPGI IDLFGVGGGL LEYRASLLAG
KGFAVMALAY YNYDDLPKNM ETMHMEYFEE AVNYLRSHPE VKGPGIGLLG ISKGGELGLA
MASFLKGITA AVVINGSVAA VGNTISYKDE TIPPVTILRN QVKMTKDGLK DVVDALQSPL
VDKKSFIPVE RSDTTFLFLV GQDDHNWKSE FYADEISKRL QAHGKEKPQI ICYPAAGHYI
EPPYFPLCSA GMHLLVGANI TFGGEPKPHA MAQLDAWQQL QTFFHKQLGS ECLHVSPKI
