ACOT4_MOUSE
ID ACOT4_MOUSE Reviewed; 421 AA.
AC Q8BWN8; Q8BJQ1; Q8BL20; Q9QYR8;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Peroxisomal succinyl-coenzyme A thioesterase {ECO:0000305|PubMed:16940157};
DE EC=3.1.2.3 {ECO:0000269|PubMed:16141203, ECO:0000269|PubMed:16940157};
DE AltName: Full=Acyl-coenzyme A thioesterase 4;
DE Short=Acyl-CoA thioesterase 4;
DE AltName: Full=PTE-2b;
DE AltName: Full=Peroxisomal acyl coenzyme A thioester hydrolase Ib;
DE AltName: Full=Peroxisomal long-chain acyl-CoA thioesterase Ib;
DE Short=PTE-Ib;
GN Name=Acot4; Synonyms=Pte1b, Pte2b;
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], TISSUE SPECIFICITY, AND INDUCTION.
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Liver;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16141203; DOI=10.1074/jbc.m508479200;
RA Westin M.A., Hunt M.C., Alexson S.E.;
RT "The identification of a succinyl-CoA thioesterase suggests a novel pathway
RT for succinate production in peroxisomes.";
RL J. Biol. Chem. 280:38125-38132(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
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-313, 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).
CC -!- FUNCTION: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids
CC and coenzyme A (CoASH), regulating their respective intracellular
CC levels (PubMed:16141203, PubMed:16940157). In contrast to its human
CC ortholog, functions essentially as a succinyl-CoA thioesterase with no
CC activity with medium to long chain saturated acyl-CoAs and with a low
CC activity toward glutaryl-CoA (PubMed:16141203, PubMed:16940157).
CC {ECO:0000269|PubMed:16141203, ECO:0000269|PubMed:16940157}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + succinyl-CoA = CoA + H(+) + succinate;
CC Xref=Rhea:RHEA:11516, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292; EC=3.1.2.3;
CC Evidence={ECO:0000269|PubMed:16141203, ECO:0000269|PubMed:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11517;
CC Evidence={ECO:0000305|PubMed:16141203, ECO:0000305|PubMed:16940157};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutaryl-CoA + H2O = CoA + glutarate + H(+);
CC Xref=Rhea:RHEA:40575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30921, ChEBI:CHEBI:57287, ChEBI:CHEBI:57378;
CC Evidence={ECO:0000269|PubMed:16141203, ECO:0000269|PubMed:16940157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40576;
CC Evidence={ECO:0000305|PubMed:16141203, ECO:0000305|PubMed:16940157};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.3 uM for succinyl-CoA {ECO:0000269|PubMed:16141203};
CC KM=37.1 uM for glutaryl-CoA {ECO:0000269|PubMed:16141203};
CC Vmax=3.98 umol/min/mg enzyme with succinyl-CoA as substrate
CC {ECO:0000269|PubMed:16141203};
CC Vmax=1.14 umol/min/mg enzyme with glutaryl-CoA as substrate
CC {ECO:0000269|PubMed:16141203};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000305|PubMed:16141203, ECO:0000305|PubMed:16940157}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:16141203}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in liver and kidney. Weakly
CC expressed in other tissues including intestine, adrenal gland and
CC adipose tissues. {ECO:0000269|PubMed:10567408,
CC ECO:0000269|PubMed:16141203, ECO:0000269|PubMed:16940157}.
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:10567408}.
CC -!- SIMILARITY: Belongs to the C/M/P thioester hydrolase family.
CC {ECO:0000305}.
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DR EMBL; AF180801; AAF13872.1; -; Genomic_DNA.
DR EMBL; AF180799; AAF13872.1; JOINED; Genomic_DNA.
DR EMBL; AF180800; AAF13872.1; JOINED; Genomic_DNA.
DR EMBL; AK046630; BAC32814.1; -; mRNA.
DR EMBL; AK050420; BAC34246.1; -; mRNA.
DR EMBL; AK080883; BAC38060.1; -; mRNA.
DR CCDS; CCDS26035.1; -.
DR RefSeq; NP_599008.3; NM_134247.3.
DR AlphaFoldDB; Q8BWN8; -.
DR SMR; Q8BWN8; -.
DR BioGRID; 228585; 1.
DR STRING; 10090.ENSMUSP00000021652; -.
DR SwissLipids; SLP:000000593; -.
DR ESTHER; mouse-acot4; Acyl-CoA_Thioesterase.
DR MEROPS; S09.A60; -.
DR iPTMnet; Q8BWN8; -.
DR PhosphoSitePlus; Q8BWN8; -.
DR SwissPalm; Q8BWN8; -.
DR jPOST; Q8BWN8; -.
DR MaxQB; Q8BWN8; -.
DR PaxDb; Q8BWN8; -.
DR PRIDE; Q8BWN8; -.
DR ProteomicsDB; 285843; -.
DR Antibodypedia; 33; 86 antibodies from 22 providers.
DR DNASU; 171282; -.
DR Ensembl; ENSMUST00000021652; ENSMUSP00000021652; ENSMUSG00000052392.
DR GeneID; 171282; -.
DR KEGG; mmu:171282; -.
DR UCSC; uc007oed.1; mouse.
DR CTD; 122970; -.
DR MGI; MGI:2159621; Acot4.
DR VEuPathDB; HostDB:ENSMUSG00000052392; -.
DR eggNOG; ENOG502QQ8Z; Eukaryota.
DR GeneTree; ENSGT01010000222336; -.
DR HOGENOM; CLU_029849_4_0_1; -.
DR InParanoid; Q8BWN8; -.
DR OMA; EDLPNNM; -.
DR OrthoDB; 1260385at2759; -.
DR PhylomeDB; Q8BWN8; -.
DR TreeFam; TF314911; -.
DR Reactome; R-MMU-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 171282; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Acot4; mouse.
DR PRO; PR:Q8BWN8; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BWN8; protein.
DR Bgee; ENSMUSG00000052392; Expressed in right kidney and 57 other tissues.
DR ExpressionAtlas; Q8BWN8; baseline and differential.
DR Genevisible; Q8BWN8; MM.
DR GO; GO:0005777; C:peroxisome; 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:0044466; F:glutaryl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0004778; F:succinyl-CoA hydrolase activity; ISO:MGI.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IDA:HGNC-UCL.
DR GO; GO:0043649; P:dicarboxylic acid catabolic process; ISO:MGI.
DR GO; GO:0043648; P:dicarboxylic acid 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; ISO:MGI.
DR GO; GO:0032788; P:saturated monocarboxylic acid metabolic process; ISO:MGI.
DR GO; GO:0046459; P:short-chain fatty acid metabolic process; IDA:HGNC-UCL.
DR GO; GO:0006104; P:succinyl-CoA metabolic process; IDA:HGNC-UCL.
DR GO; GO:0032789; P:unsaturated monocarboxylic acid metabolic process; ISO:MGI.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic 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 Fatty acid metabolism; Hydrolase; Lipid metabolism; Peroxisome;
KW Reference proteome; Serine esterase.
FT CHAIN 1..421
FT /note="Peroxisomal succinyl-coenzyme A thioesterase"
FT /id="PRO_0000202150"
FT MOTIF 419..421
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 232
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P49753"
FT ACT_SITE 326
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P49753"
FT ACT_SITE 360
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P49753"
FT MOD_RES 313
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 87
FT /note="D -> N (in Ref. 2; BAC32814)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="R -> G (in Ref. 1; AAF13872)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="M -> K (in Ref. 2; BAC38060)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 46481 MW; 93DB75F0191D49F7 CRC64;
MAATLSVEPT GRSCWDEPLS IAVRGLAPEQ PVTLRSVLRD EKGALFRAHA RYRADSHGEL
DLARVPALGG SFSGLEPMGL LWAMEPDRPF WRLIKRDVQT PFLVELEVLD GHEPDGGRRL
ARTVHERHFM APGVRRVPVR EGRVRATLFL PPGQGPFPGI IDVYGVGGGL LEYRAGLVAG
HGFATLALAF YDFEDLPKEL NVIEVDYFEE AVRYMLRHPK VKGPDIGLLG LSLGADVCLI
MASFLNNVSA TVSINGSAFS GNRHIKYKQT MIPPLGHDLR RMKVAFSGIL DIVDIRNDAV
GGCENPSMIP IEKAKGPILF VAGQDDHCWR SELYTQIASD RLQAHGKERP QVLSYPGTGH
YIEPPYFPMC PASLHKIVNE AVIWGGEVKA HSKAQIDAWK QILFFFGKHL GSTHSRASCR
L
