ACOT2_MOUSE
ID ACOT2_MOUSE Reviewed; 453 AA.
AC Q9QYR9; Q3T9C9;
DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Acyl-coenzyme A thioesterase 2, mitochondrial;
DE Short=Acyl-CoA thioesterase 2;
DE EC=3.1.2.2 {ECO:0000269|PubMed:25114170};
DE AltName: Full=Acyl coenzyme A thioester hydrolase;
DE AltName: Full=MTE-I;
DE AltName: Full=Very-long-chain acyl-CoA thioesterase;
DE Flags: Precursor;
GN Name=Acot2; Synonyms=Mte1;
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 [GENOMIC DNA], CHARACTERIZATION, INDUCTION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J;
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 [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen;
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).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-447, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-83, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J;
RX PubMed=25114170; DOI=10.1194/jlr.m046961;
RA Moffat C., Bhatia L., Nguyen T., Lynch P., Wang M., Wang D., Ilkayeva O.R.,
RA Han X., Hirschey M.D., Claypool S.M., Seifert E.L.;
RT "Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in
RT the liver.";
RL J. Lipid Res. 55:2458-2470(2014).
CC -!- FUNCTION: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids
CC and coenzyme A (CoASH), regulating their respective intracellular
CC levels (PubMed:25114170). Displays higher activity toward long chain
CC acyl CoAs (C14-C20) (PubMed:25114170). The enzyme is involved in
CC enhancing the hepatic fatty acid oxidation in mitochondria
CC (PubMed:25114170). {ECO:0000269|PubMed:25114170}.
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:25114170};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000269|PubMed:25114170};
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:25114170};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000269|PubMed:25114170};
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:0000250|UniProtKB:P49753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30140;
CC Evidence={ECO:0000250|UniProtKB:P49753};
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:0000250|UniProtKB:P49753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40148;
CC Evidence={ECO:0000250|UniProtKB:P49753};
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:P49753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000250|UniProtKB:P49753};
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:P49753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000250|UniProtKB:P49753};
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:25114170};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000269|PubMed:25114170};
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:0000250|UniProtKB:P49753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40132;
CC Evidence={ECO:0000250|UniProtKB:P49753};
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:0000250|UniProtKB:P49753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40724;
CC Evidence={ECO:0000250|UniProtKB:P49753};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + H2O = (9Z,12Z)-octadecadienoate
CC + CoA + H(+); Xref=Rhea:RHEA:40143, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57383; Evidence={ECO:0000269|PubMed:25114170};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40144;
CC Evidence={ECO:0000269|PubMed:25114170};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:25114170}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:25114170}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:25114170}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brown and white adipose tissue,
CC muscle, heart, kidney, lung, adrenal gland and spleen; weakly expressed
CC in intestine, testis and brain. {ECO:0000269|PubMed:10567408,
CC 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; AF180798; AAF13871.1; -; Genomic_DNA.
DR EMBL; AF180796; AAF13871.1; JOINED; Genomic_DNA.
DR EMBL; AF180797; AAF13871.1; JOINED; Genomic_DNA.
DR EMBL; AK172617; BAE43095.1; -; mRNA.
DR EMBL; CH466590; EDL02755.1; -; Genomic_DNA.
DR CCDS; CCDS26034.1; -.
DR RefSeq; NP_598949.3; NM_134188.3.
DR AlphaFoldDB; Q9QYR9; -.
DR SMR; Q9QYR9; -.
DR IntAct; Q9QYR9; 1.
DR STRING; 10090.ENSMUSP00000021649; -.
DR ChEMBL; CHEMBL3259488; -.
DR ESTHER; mouse-acot2; Acyl-CoA_Thioesterase.
DR MEROPS; S09.A52; -.
DR iPTMnet; Q9QYR9; -.
DR PhosphoSitePlus; Q9QYR9; -.
DR EPD; Q9QYR9; -.
DR jPOST; Q9QYR9; -.
DR MaxQB; Q9QYR9; -.
DR PaxDb; Q9QYR9; -.
DR PeptideAtlas; Q9QYR9; -.
DR PRIDE; Q9QYR9; -.
DR ProteomicsDB; 285648; -.
DR DNASU; 171210; -.
DR Ensembl; ENSMUST00000021649; ENSMUSP00000021649; ENSMUSG00000021226.
DR GeneID; 171210; -.
DR KEGG; mmu:171210; -.
DR UCSC; uc011yor.1; mouse.
DR CTD; 10965; -.
DR MGI; MGI:2159605; Acot2.
DR VEuPathDB; HostDB:ENSMUSG00000021226; -.
DR eggNOG; ENOG502QQ8Z; Eukaryota.
DR GeneTree; ENSGT01010000222336; -.
DR HOGENOM; CLU_029849_4_0_1; -.
DR InParanoid; Q9QYR9; -.
DR OMA; CQWGWKS; -.
DR OrthoDB; 1260385at2759; -.
DR PhylomeDB; Q9QYR9; -.
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 UniPathway; UPA00199; -.
DR BioGRID-ORCS; 171210; 2 hits in 76 CRISPR screens.
DR PRO; PR:Q9QYR9; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9QYR9; protein.
DR Bgee; ENSMUSG00000021226; Expressed in interventricular septum and 229 other tissues.
DR Genevisible; Q9QYR9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; ISO: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; ISO:MGI.
DR GO; GO:0006637; P:acyl-CoA metabolic process; ISO:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0042760; P:very long-chain fatty acid catabolic 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 Acetylation; Fatty acid metabolism; Hydrolase; Lipid metabolism;
KW Mitochondrion; Reference proteome; Serine esterase; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 43..453
FT /note="Acyl-coenzyme A thioesterase 2, mitochondrial"
FT /id="PRO_0000034065"
FT ACT_SITE 273
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P49753"
FT ACT_SITE 365
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P49753"
FT ACT_SITE 399
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P49753"
FT MOD_RES 83
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 447
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 163
FT /note="Q -> H (in Ref. 1; AAF13871)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="L -> V (in Ref. 1; AAF13871)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 453 AA; 49657 MW; 5687F2363B16284B CRC64;
MVASSFAVLR ASRLCQQDWK SWARLFVPPP LSTGGRTTWA RTNATLSVEP EGRSCWDEPL
SIAVRGLAPE QPVTLRSALR DEKGALFRAH ARYRADAGGE LNLARAPALG GSFSGLEPMG
LLWAMEPERP LWRLIKRDVQ TPFLVELEVL DGHEPDGGQR LAQAVHERHF LAPGVRRVPV
REGRVRATLF LPPEPGPFPG IIDLFGVGGG LLEYRASLLA GKGFAVMALA YYNYDDLPKS
IETMHMEYFE EAVNYLRSHP EVKGPGIGLL GISKGGELGL AMASFLKGIT AAVVINGSVA
AVGNTISYKD ETIPPVSLLR NQVKMTKDGL LDVVEALQSP LVDKKSFIPV ERSDTTFLFL
VGQDDHNWKS EFYADEISKR LQAHGKEKPQ IICYPAAGHY IEPPYFPLCS AGMHLLVGAN
ITFGGEPRAH AVAQVDAWQQ LQTFFHKQLG SKS
