THEM5_MOUSE
ID THEM5_MOUSE Reviewed; 248 AA.
AC Q9CQJ0; Q9CTI2;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Acyl-coenzyme A thioesterase THEM5;
DE Short=Acyl-CoA thioesterase THEM5;
DE EC=3.1.2.2 {ECO:0000250|UniProtKB:Q8N1Q8};
DE AltName: Full=Acyl-coenzyme A thioesterase 15;
DE AltName: Full=Thioesterase superfamily member 5;
GN Name=Them5; Synonyms=Acot15;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 92-248 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=22586271; DOI=10.1128/mcb.00312-12;
RA Zhuravleva E., Gut H., Hynx D., Marcellin D., Bleck C.K., Genoud C.,
RA Cron P., Keusch J.J., Dummler B., Esposti M.D., Hemmings B.A.;
RT "Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin
RT remodeling and fatty liver development.";
RL Mol. Cell. Biol. 32:2685-2697(2012).
CC -!- FUNCTION: Has acyl-CoA thioesterase activity towards long-chain (C16
CC and C18) fatty acyl-CoA substrates, with a preference for linoleoyl-CoA
CC and other unsaturated long-chain fatty acid-CoA esters (By similarity).
CC Plays an important role in mitochondrial fatty acid metabolism, and in
CC remodeling of the mitochondrial lipid cardiolipin (PubMed:22586271).
CC Required for normal mitochondrial function (PubMed:22586271).
CC {ECO:0000250|UniProtKB:Q8N1Q8, ECO:0000269|PubMed:22586271}.
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:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
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:0000250|UniProtKB:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40144;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
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:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
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:0000250|UniProtKB:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
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:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40132;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + CoA + H(+); Xref=Rhea:RHEA:40151,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57368;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40152;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
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:Q8N1Q8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30140;
CC Evidence={ECO:0000250|UniProtKB:Q8N1Q8};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8N1Q8}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q8N1Q8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CQJ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CQJ0-2; Sequence=VSP_024556;
CC -!- DISRUPTION PHENOTYPE: With increasing age, mice develop fatty liver,
CC due to impaired mitochondrial fatty acid metabolism, and impaired
CC remodeling of the mitochondrial lipid cardiolipin. Mitochondria contain
CC increased levels of monolysocardiolipin, and decreased levels of
CC linoleic and linolenic acid. The altered fatty acid metabolism leads to
CC decreased mitochondrial beta-oxidation and ketone body formation.
CC Mitochondria show abnormal, elongated morphology, and their function is
CC impaired. {ECO:0000269|PubMed:22586271}.
CC -!- SIMILARITY: Belongs to the THEM4/THEM5 thioesterase family.
CC {ECO:0000305}.
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DR EMBL; AK003517; BAB22830.1; -; mRNA.
DR EMBL; AK004155; BAB23196.1; -; mRNA.
DR EMBL; AK009228; BAB26151.1; -; mRNA.
DR EMBL; BC046437; AAH46437.1; -; mRNA.
DR CCDS; CCDS17590.1; -. [Q9CQJ0-1]
DR RefSeq; NP_079692.1; NM_025416.3. [Q9CQJ0-1]
DR AlphaFoldDB; Q9CQJ0; -.
DR SMR; Q9CQJ0; -.
DR STRING; 10090.ENSMUSP00000029794; -.
DR PhosphoSitePlus; Q9CQJ0; -.
DR MaxQB; Q9CQJ0; -.
DR PaxDb; Q9CQJ0; -.
DR PRIDE; Q9CQJ0; -.
DR ProteomicsDB; 285592; -. [Q9CQJ0-1]
DR ProteomicsDB; 285593; -. [Q9CQJ0-2]
DR Antibodypedia; 34076; 64 antibodies from 13 providers.
DR Ensembl; ENSMUST00000029794; ENSMUSP00000029794; ENSMUSG00000028148. [Q9CQJ0-1]
DR GeneID; 66198; -.
DR KEGG; mmu:66198; -.
DR UCSC; uc008qfv.2; mouse. [Q9CQJ0-1]
DR UCSC; uc008qfw.1; mouse. [Q9CQJ0-2]
DR CTD; 284486; -.
DR MGI; MGI:1913448; Them5.
DR VEuPathDB; HostDB:ENSMUSG00000028148; -.
DR eggNOG; KOG4781; Eukaryota.
DR GeneTree; ENSGT00940000161937; -.
DR HOGENOM; CLU_072603_0_0_1; -.
DR InParanoid; Q9CQJ0; -.
DR OMA; QVEGQGY; -.
DR OrthoDB; 1322443at2759; -.
DR PhylomeDB; Q9CQJ0; -.
DR TreeFam; TF332518; -.
DR Reactome; R-MMU-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR BioGRID-ORCS; 66198; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Them5; mouse.
DR PRO; PR:Q9CQJ0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9CQJ0; protein.
DR Bgee; ENSMUSG00000028148; Expressed in tail skin and 56 other tissues.
DR ExpressionAtlas; Q9CQJ0; baseline and differential.
DR Genevisible; Q9CQJ0; MM.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0102991; F:myristoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; ISS:UniProtKB.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; IMP:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; ISS:UniProtKB.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR006683; Thioestr_dom.
DR Pfam; PF03061; 4HBT; 1.
DR SUPFAM; SSF54637; SSF54637; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Fatty acid metabolism; Hydrolase; Lipid metabolism;
KW Mitochondrion; Reference proteome.
FT CHAIN 1..248
FT /note="Acyl-coenzyme A thioesterase THEM5"
FT /id="PRO_0000284520"
FT ACT_SITE 167
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT VAR_SEQ 235..248
FT /note="VFLQLQLEEQSQEQ -> KEICSLSLGCLPLPHPQQRVGKMSAKSQILSWSL
FT GLLGVEMLLARDMDEEKGNKVRITQPAPQDSLK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_024556"
SQ SEQUENCE 248 AA; 27865 MW; 86A6C91ED6FCEB73 CRC64;
MLRTSFQGVA RLVRHKALYR SPCLLPRVHL ASAFGSSTES LVARFCPEKT DLKDYALPNA
SWCSDMLSLY QEFLEKTKSG GWIKLPSFKS NRDHIQGLKL PFGLETASDK QDWRLFTRSI
QLEGQGYEYV IFFHPSEKKS VCLFQPGPYL EGAPGFAHGG SLAALMDETY SKTAYLAGEG
LFTLSLNIKF KNLIPVGSLA VLDIQVEKIE DQKLYMSCIA QSRDKQTVYA KSSGVFLQLQ
LEEQSQEQ
