ACOT1_HUMAN
ID ACOT1_HUMAN Reviewed; 421 AA.
AC Q86TX2; A1L173; Q3I5F9;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Acyl-coenzyme A thioesterase 1 {ECO:0000305|PubMed:16940157};
DE Short=Acyl-CoA thioesterase 1 {ECO:0000305|PubMed:16940157};
DE EC=3.1.2.- {ECO:0000269|PubMed:16940157};
DE AltName: Full=CTE-I;
DE AltName: Full=CTE-Ib;
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:0000305|PubMed:16940157};
DE EC=3.1.2.2 {ECO:0000269|PubMed:16940157};
GN Name=ACOT1; Synonyms=CTE1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE
RP SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16940157; DOI=10.1096/fj.06-6042com;
RA Hunt M.C., Rautanen A., Westin M.A.K., Svensson L.T., Alexson S.E.H.;
RT "Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters
RT shows that convergent, functional evolution results in a reduced number of
RT human peroxisomal ACOTs.";
RL FASEB J. 20:1855-1864(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuroblastoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 2-12; 25-35 AND 223-233, CLEAVAGE OF INITIATOR
RP METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
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:16940157}.
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30140;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40148;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40132;
CC Evidence={ECO:0000305|PubMed:16940157};
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:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40724;
CC Evidence={ECO:0000305|PubMed:16940157};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=35.8 uM for C10-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=3.6 uM for C12-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=2.8 uM for C14-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=3.6 uM for C16-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=2.4 uM for C18-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=2 uM for C20-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=2.4 uM for C16:1-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=4.1 uM for C18:1-acyl-CoA {ECO:0000269|PubMed:16940157};
CC KM=2.1 uM for C18:1-trans-acyl-CoA {ECO:0000269|PubMed:16940157};
CC Vmax=224 nmol/min/mg enzyme toward C10-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=700 nmol/min/mg enzyme toward C12-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=912 nmol/min/mg enzyme toward C14-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=691 nmol/min/mg enzyme toward C16-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=597 nmol/min/mg enzyme toward C18-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=520 nmol/min/mg enzyme toward C20-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=577 nmol/min/mg enzyme toward C16:1-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=258 nmol/min/mg enzyme toward C18:1-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC Vmax=309 nmol/min/mg enzyme toward C18:1-trans-acyl-CoA
CC {ECO:0000269|PubMed:16940157};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000305|PubMed:16940157}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16940157}.
CC -!- SIMILARITY: Belongs to the C/M/P thioester hydrolase 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; DQ082754; AAZ31236.1; -; mRNA.
DR EMBL; BX161396; CAD61883.1; -; mRNA.
DR EMBL; BC127748; AAI27749.1; -; mRNA.
DR EMBL; BC132889; AAI32890.1; -; mRNA.
DR EMBL; BC132891; AAI32892.1; -; mRNA.
DR EMBL; BC143042; AAI43043.1; -; mRNA.
DR CCDS; CCDS32117.1; -.
DR RefSeq; NP_001032238.1; NM_001037161.1.
DR AlphaFoldDB; Q86TX2; -.
DR SMR; Q86TX2; -.
DR BioGRID; 534965; 116.
DR IntAct; Q86TX2; 18.
DR MINT; Q86TX2; -.
DR STRING; 9606.ENSP00000311224; -.
DR ChEMBL; CHEMBL2189136; -.
DR SwissLipids; SLP:000000613; -.
DR ESTHER; human-ACOT1; Acyl-CoA_Thioesterase.
DR iPTMnet; Q86TX2; -.
DR PhosphoSitePlus; Q86TX2; -.
DR SwissPalm; Q86TX2; -.
DR BioMuta; ACOT1; -.
DR DMDM; 50428913; -.
DR UCD-2DPAGE; Q86TX2; -.
DR EPD; Q86TX2; -.
DR jPOST; Q86TX2; -.
DR MassIVE; Q86TX2; -.
DR MaxQB; Q86TX2; -.
DR PaxDb; Q86TX2; -.
DR PeptideAtlas; Q86TX2; -.
DR PRIDE; Q86TX2; -.
DR ProteomicsDB; 69743; -.
DR Antibodypedia; 54875; 106 antibodies from 21 providers.
DR DNASU; 641371; -.
DR Ensembl; ENST00000311148.9; ENSP00000311224.4; ENSG00000184227.8.
DR GeneID; 641371; -.
DR KEGG; hsa:641371; -.
DR MANE-Select; ENST00000311148.9; ENSP00000311224.4; NM_001037161.2; NP_001032238.1.
DR UCSC; uc001xol.2; human.
DR CTD; 641371; -.
DR DisGeNET; 641371; -.
DR GeneCards; ACOT1; -.
DR HGNC; HGNC:33128; ACOT1.
DR HPA; ENSG00000184227; Tissue enhanced (liver).
DR MIM; 614313; gene.
DR neXtProt; NX_Q86TX2; -.
DR OpenTargets; ENSG00000184227; -.
DR PharmGKB; PA162375318; -.
DR VEuPathDB; HostDB:ENSG00000184227; -.
DR eggNOG; ENOG502QQ8Z; Eukaryota.
DR GeneTree; ENSGT01010000222336; -.
DR HOGENOM; CLU_029849_4_0_1; -.
DR InParanoid; Q86TX2; -.
DR OMA; IVFPYVP; -.
DR OrthoDB; 991383at2759; -.
DR PhylomeDB; Q86TX2; -.
DR TreeFam; TF314911; -.
DR BioCyc; MetaCyc:MON-14105; -.
DR BRENDA; 3.1.2.2; 2681.
DR PathwayCommons; Q86TX2; -.
DR Reactome; R-HSA-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR SABIO-RK; Q86TX2; -.
DR SignaLink; Q86TX2; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 641371; 10 hits in 997 CRISPR screens.
DR ChiTaRS; ACOT1; human.
DR GenomeRNAi; 641371; -.
DR Pharos; Q86TX2; Tbio.
DR PRO; PR:Q86TX2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86TX2; protein.
DR Bgee; ENSG00000184227; Expressed in right lobe of liver and 101 other tissues.
DR ExpressionAtlas; Q86TX2; baseline and differential.
DR Genevisible; Q86TX2; HS.
DR GO; GO:0005829; C:cytosol; IDA:HGNC-UCL.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; IDA:HGNC-UCL.
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; IDA:HGNC-UCL.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:HGNC-UCL.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IDA:HGNC-UCL.
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; Direct protein sequencing; Fatty acid metabolism; Hydrolase;
KW Lipid metabolism; Reference proteome; Serine esterase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4"
FT CHAIN 2..421
FT /note="Acyl-coenzyme A thioesterase 1"
FT /id="PRO_0000202155"
FT ACT_SITE 232
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 326
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 360
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT VARIANT 266
FT /note="R -> H (in dbSNP:rs1049568)"
FT /id="VAR_059830"
SQ SEQUENCE 421 AA; 46277 MW; 04675F28D9D53B97 CRC64;
MAATLILEPA GRCCWDEPVR IAVRGLAPEQ PVTLRASLRD EKGALFQAHA RYRADTLGEL
DLERAPALGG SFAGLEPMGL LWALEPEKPL VRLVKRDVRT PLAVELEVLD GHDPDPGRLL
CRVRHERYFL PPGVRREPVR AGRVRGTLFL PPEPGPFPGI VDMFGTGGGL LEYRASLLAG
KGFAVMALAY YNYEDLPKTM ETLHLEYFEE AVNYLLSHPE VKGPGVGLLG ISKGGELCLS
MASFLKGITA AVVINGSVAN VGGTLRYKGE TLPPVGVNRN RIKVTKDGYA DIVDVLNSPL
EGPDQKSFIP VERAESTFLF LVGQDDHNWK SEFYANEACK RLQAHGRRKP QIICYPETGH
YIEPPYFPLC RASLHALVGS PIIWGGEPRA HAMAQVDAWK QLQTFFHKHL GGHEGTIPSK
V
