THEM4_MOUSE
ID THEM4_MOUSE Reviewed; 230 AA.
AC Q3UUI3; A3KPD5; Q8BYS9; Q8R234; Q9D5Y3;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Acyl-coenzyme A thioesterase THEM4;
DE Short=Acyl-CoA thioesterase THEM4;
DE EC=3.1.2.2 {ECO:0000250|UniProtKB:Q5T1C6};
DE AltName: Full=Carboxyl-terminal modulator protein;
DE AltName: Full=Thioesterase superfamily member 4;
DE Flags: Precursor;
GN Name=Them4; Synonyms=Ctmp;
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].
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus, and Testis;
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].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 INTERACTION WITH AKT8 MURINE LEUKEMIA VIRUS V-AKT (MICROBIAL INFECTION) AND
RP AKTI.
RX PubMed=11598301; DOI=10.1126/science.1062030;
RA Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M.,
RA Hemmings B.A.;
RT "Carboxyl-terminal modulator protein (CTMP), a negative regulator of
RT PKB/Akt and v-Akt at the plasma membrane.";
RL Science 294:374-380(2001).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19421406; DOI=10.1371/journal.pone.0005471;
RA Parcellier A., Tintignac L.A., Zhuravleva E., Dummler B., Brazil D.P.,
RA Hynx D., Cron P., Schenk S., Olivieri V., Hemmings B.A.;
RT "The carboxy-terminal modulator protein (CTMP) regulates mitochondrial
RT dynamics.";
RL PLoS ONE 4:E5471-E5471(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, 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).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-46; LYS-57; LYS-89; LYS-98 AND
RP LYS-197, AND IDENTIFICATION BY MASS 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-65, 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).
CC -!- FUNCTION: Has acyl-CoA thioesterase activity towards medium and long-
CC chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a role
CC in mitochondrial fatty acid metabolism (By similarity). Plays a role in
CC the apoptotic process, possibly via its regulation of AKT1 activity
CC (PubMed:19421406). {ECO:0000250|UniProtKB:Q5T1C6,
CC ECO:0000269|PubMed:19421406}.
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:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + octanoyl-CoA = CoA + H(+) + octanoate;
CC Xref=Rhea:RHEA:30143, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:25646, ChEBI:CHEBI:57287, ChEBI:CHEBI:57386;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30144;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
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:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
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:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
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:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
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:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
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:Q5T1C6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40152;
CC Evidence={ECO:0000250|UniProtKB:Q5T1C6};
CC -!- SUBUNIT: Homodimer and homotetramer (By similarity). Interacts with
CC AKT1 in the cytosol (PubMed:11598301). {ECO:0000250|UniProtKB:Q5T1C6,
CC ECO:0000269|PubMed:11598301}.
CC -!- SUBUNIT: (Microbial infection) Interacts with V-AKT from AKT8 murine
CC leukemia virus. {ECO:0000269|PubMed:11598301}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q5T1C6}.
CC Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q5T1C6}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q5T1C6}. Mitochondrion
CC {ECO:0000269|PubMed:19421406}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q5T1C6}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q5T1C6}. Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:Q5T1C6}. Note=Released from the mitochondria
CC into the cytosol in response to apoptotic stimuli.
CC {ECO:0000250|UniProtKB:Q5T1C6}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q5T1C6}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice have abnormally
CC elongated mitochondria, but mitochondrial function appears to be
CC normal. {ECO:0000269|PubMed:19421406}.
CC -!- SIMILARITY: Belongs to the THEM4/THEM5 thioesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI34397.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAB29572.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAC29995.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AK014834; BAB29572.1; ALT_SEQ; mRNA.
DR EMBL; AK038420; BAC29995.1; ALT_SEQ; mRNA.
DR EMBL; AK138397; BAE23642.1; -; mRNA.
DR EMBL; BC022612; AAH22612.1; -; mRNA.
DR EMBL; BC134396; AAI34397.1; ALT_SEQ; mRNA.
DR CCDS; CCDS38533.1; -.
DR RefSeq; NP_083707.1; NM_029431.1.
DR AlphaFoldDB; Q3UUI3; -.
DR SMR; Q3UUI3; -.
DR BioGRID; 217735; 1.
DR STRING; 10090.ENSMUSP00000062841; -.
DR iPTMnet; Q3UUI3; -.
DR PhosphoSitePlus; Q3UUI3; -.
DR SwissPalm; Q3UUI3; -.
DR EPD; Q3UUI3; -.
DR jPOST; Q3UUI3; -.
DR MaxQB; Q3UUI3; -.
DR PaxDb; Q3UUI3; -.
DR PeptideAtlas; Q3UUI3; -.
DR PRIDE; Q3UUI3; -.
DR ProteomicsDB; 259381; -.
DR Antibodypedia; 34077; 86 antibodies from 28 providers.
DR Ensembl; ENSMUST00000049822; ENSMUSP00000062841; ENSMUSG00000028145.
DR GeneID; 75778; -.
DR KEGG; mmu:75778; -.
DR UCSC; uc008qft.1; mouse.
DR CTD; 117145; -.
DR MGI; MGI:1923028; Them4.
DR VEuPathDB; HostDB:ENSMUSG00000028145; -.
DR eggNOG; KOG4781; Eukaryota.
DR GeneTree; ENSGT00940000160047; -.
DR HOGENOM; CLU_072603_0_1_1; -.
DR InParanoid; Q3UUI3; -.
DR OMA; MFYNDVE; -.
DR OrthoDB; 1322443at2759; -.
DR PhylomeDB; Q3UUI3; -.
DR TreeFam; TF332518; -.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-165158; Activation of AKT2.
DR Reactome; R-MMU-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-MMU-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR BioGRID-ORCS; 75778; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Them4; mouse.
DR PRO; PR:Q3UUI3; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q3UUI3; protein.
DR Bgee; ENSMUSG00000028145; Expressed in spermatocyte and 244 other tissues.
DR Genevisible; Q3UUI3; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
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:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:1902108; P:regulation of mitochondrial membrane permeability involved in apoptotic 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 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cell membrane; Cell projection; Cytoplasm;
KW Fatty acid metabolism; Host-virus interaction; Hydrolase; Lipid metabolism;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 28..230
FT /note="Acyl-coenzyme A thioesterase THEM4"
FT /id="PRO_0000314180"
FT ACT_SITE 152
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q5T1C6"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 196..197
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T1C6"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T1C6"
FT MOD_RES 46
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 57
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 65
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 89
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 98
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 197
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 34
FT /note="R -> C (in Ref. 2; AAH22612)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="M -> V (in Ref. 1; BAB29572)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 230 AA; 26031 MW; B0FFCCDBB1E45CEE CRC64;
MLRNCAMRLR TLGATPARRP GAARRLFSSE KVIRKDYALP NPSWTKDLRL LFDQFMKKCE
DGSWKRMPSH RQNPTRAIQE FQTLFVDSKF KKEEQMSKAQ QFTRSFEEGL GFEYAMFYNK
VEKRTVSLFQ GGLHLQGVPG FVHGGAIATI IDVTTGTCAI SEGVAMTANL NITYKKPIPL
LSVVVVNSQL QKIEGRKLFV SCTIQSIDEK TLYTEATALF IKLDPEKPLT
