THEM4_HUMAN
ID THEM4_HUMAN Reviewed; 240 AA.
AC Q5T1C6; B2RBX2; Q96KR2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Acyl-coenzyme A thioesterase THEM4;
DE Short=Acyl-CoA thioesterase THEM4;
DE EC=3.1.2.2 {ECO:0000269|PubMed:19453107, ECO:0000269|PubMed:22871024};
DE AltName: Full=Carboxyl-terminal modulator protein;
DE AltName: Full=Thioesterase superfamily member 4;
DE Flags: Precursor;
GN Name=THEM4; Synonyms=CTMP;
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, INTERACTION WITH AKT1, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND VARIANT ARG-17.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-17.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-17.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-17.
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=15026474; DOI=10.1093/jnci/djh064;
RA Knobbe C.B., Reifenberger J., Blaschke B., Reifenberger G.;
RT "Hypermethylation and transcriptional downregulation of the carboxyl-
RT terminal modulator protein gene in glioblastomas.";
RL J. Natl. Cancer Inst. 96:483-486(2004).
RN [7]
RP FUNCTION.
RX PubMed=17615157; DOI=10.1152/ajpcell.00570.2006;
RA Ono H., Sakoda H., Fujishiro M., Anai M., Kushiyama A., Fukushima Y.,
RA Katagiri H., Ogihara T., Oka Y., Kamata H., Horike N., Uchijima Y.,
RA Kurihara H., Asano T.;
RT "Carboxy-terminal modulator protein induces Akt phosphorylation and
RT activation, thereby enhancing antiapoptotic, glycogen synthetic, and
RT glucose uptake pathways.";
RL Am. J. Physiol. 293:C1576-C1585(2007).
RN [8]
RP PHOSPHORYLATION AT SER-37 AND SER-38, IDENTIFICATION BY MASS SPECTROMETRY,
RP MUTAGENESIS OF 37-SER-SER-38, AND SUBCELLULAR LOCATION.
RX PubMed=19604401; DOI=10.1186/1471-2121-10-53;
RA Piao L., Li Y., Yang K.J., Park K.A., Byun H.S., Won M., Hong J., Kim J.L.,
RA Kweon G.R., Hur G.M., Seok J.H., Cho J.Y., Chun T., Hess D., Sack R.,
RA Maira S.M., Brazil D.P., Hemmings B.A., Park J.;
RT "Heat shock protein 70-mediated sensitization of cells to apoptosis by
RT carboxyl-terminal modulator protein.";
RL BMC Cell Biol. 10:53-53(2009).
RN [9]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19453107; DOI=10.1021/bi900710w;
RA Zhao H., Martin B.M., Bisoffi M., Dunaway-Mariano D.;
RT "The Akt C-terminal modulator protein is an acyl-CoA thioesterase of the
RT Hotdog-Fold family.";
RL Biochemistry 48:5507-5509(2009).
RN [10]
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF SER-37.
RX PubMed=19168129; DOI=10.1016/j.cellsig.2009.01.016;
RA Parcellier A., Tintignac L.A., Zhuravleva E., Cron P., Schenk S.,
RA Bozulic L., Hemmings B.A.;
RT "Carboxy-terminal modulator protein (CTMP) is a mitochondrial protein that
RT sensitizes cells to apoptosis.";
RL Cell. Signal. 21:639-650(2009).
RN [11]
RP 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 [12]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 40-240 IN COMPLEX WITH
RP UNDECAN-2-ONE-COA, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, FUNCTION, ACTIVE SITE, INTERACTION WITH AKT1, AND MUTAGENESIS OF
RP HIS-152; ASP-161; THR-177; ASN-183; ARG-206 AND LYS-207.
RX PubMed=22871024; DOI=10.1021/bi300968n;
RA Zhao H., Lim K., Choudry A., Latham J.A., Pathak M.C., Dominguez D.,
RA Luo L., Herzberg O., Dunaway-Mariano D.;
RT "Correlation of structure and function in the human hotdog-fold enzyme
RT hTHEM4.";
RL Biochemistry 51:6490-6492(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 37-240, AND SUBUNIT.
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).
RN [14]
RP VARIANTS ARG-17 AND CYS-38.
RX PubMed=17013611; DOI=10.1007/s00401-006-0128-y;
RA Schick V., Majores M., Engels G., Spitoni S., Koch A., Elger C.E.,
RA Simon M., Knobbe C., Bluemcke I., Becker A.J.;
RT "Activation of Akt independent of PTEN and CTMP tumor-suppressor gene
RT mutations in epilepsy-associated Taylor-type focal cortical dysplasias.";
RL Acta Neuropathol. 112:715-725(2006).
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. Plays a role in the apoptotic
CC process, possibly via its regulation of AKT1 activity. According to
CC PubMed:11598301, inhibits AKT1 phosphorylation and activity. According
CC to PubMed:17615157, enhances AKT1 activity by favoring its
CC phosphorylation and translocation to plasma membrane.
CC {ECO:0000269|PubMed:11598301, ECO:0000269|PubMed:17615157,
CC ECO:0000269|PubMed:19168129, ECO:0000269|PubMed:19421406,
CC ECO:0000269|PubMed:19453107, ECO:0000269|PubMed:22871024}.
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:19453107, ECO:0000269|PubMed:22871024};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:19453107};
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:0000269|PubMed:19453107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30144;
CC Evidence={ECO:0000305|PubMed:19453107};
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:19453107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000305|PubMed:19453107};
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:19453107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000305|PubMed:19453107};
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:19453107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000305|PubMed:19453107};
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:19453107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000305|PubMed:19453107};
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:0000269|PubMed:19453107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40152;
CC Evidence={ECO:0000305|PubMed:19453107};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.4 uM for myristoyl-CoA {ECO:0000269|PubMed:19453107,
CC ECO:0000269|PubMed:22871024};
CC KM=2.6 uM for palmitoyl-CoA {ECO:0000269|PubMed:19453107,
CC ECO:0000269|PubMed:22871024};
CC KM=5.2 uM for oleoyl-CoA {ECO:0000269|PubMed:19453107,
CC ECO:0000269|PubMed:22871024};
CC -!- SUBUNIT: Homodimer and homotetramer. Interacts with AKT1 in the
CC cytosol. {ECO:0000269|PubMed:11598301, ECO:0000269|PubMed:22586271,
CC ECO:0000269|PubMed:22871024}.
CC -!- INTERACTION:
CC Q5T1C6; P31749: AKT1; NbExp=4; IntAct=EBI-7684443, EBI-296087;
CC Q5T1C6; P22607: FGFR3; NbExp=3; IntAct=EBI-7684443, EBI-348399;
CC Q5T1C6; P01112: HRAS; NbExp=3; IntAct=EBI-7684443, EBI-350145;
CC Q5T1C6; P16284: PECAM1; NbExp=3; IntAct=EBI-7684443, EBI-716404;
CC Q5T1C6; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-7684443, EBI-5235340;
CC Q5T1C6; P08670: VIM; NbExp=3; IntAct=EBI-7684443, EBI-353844;
CC Q5T1C6; Q9Y649; NbExp=3; IntAct=EBI-7684443, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11598301}. Cell
CC projection, ruffle membrane {ECO:0000269|PubMed:11598301}. Cytoplasm
CC {ECO:0000269|PubMed:19604401}. Mitochondrion
CC {ECO:0000269|PubMed:19168129, ECO:0000269|PubMed:19421406,
CC ECO:0000269|PubMed:19604401}. Mitochondrion inner membrane; Peripheral
CC membrane protein {ECO:0000269|PubMed:19168129}. Mitochondrion
CC intermembrane space {ECO:0000269|PubMed:19168129,
CC ECO:0000269|PubMed:19604401}. Note=Released from the mitochondria into
CC the cytosol in response to apoptotic stimuli.
CC {ECO:0000269|PubMed:19168129}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in skeletal muscle, testis,
CC uterus, brain and kidney. Down-regulated in glioblastoma or glioma
CC compared to non-neoplastic brain due to promoter hypermethylation.
CC {ECO:0000269|PubMed:11598301, ECO:0000269|PubMed:15026474}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:11598301,
CC ECO:0000269|PubMed:19604401}.
CC -!- SIMILARITY: Belongs to the THEM4/THEM5 thioesterase family.
CC {ECO:0000305}.
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DR EMBL; AJ313515; CAC86384.1; -; mRNA.
DR EMBL; AK314852; BAG37369.1; -; mRNA.
DR EMBL; AL450992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53400.1; -; Genomic_DNA.
DR EMBL; BC065277; AAH65277.1; -; mRNA.
DR CCDS; CCDS1006.1; -.
DR RefSeq; NP_444283.2; NM_053055.4.
DR PDB; 4AE8; X-ray; 1.59 A; A/B/C/D=37-240.
DR PDB; 4GAH; X-ray; 2.30 A; A/B=40-240.
DR PDBsum; 4AE8; -.
DR PDBsum; 4GAH; -.
DR AlphaFoldDB; Q5T1C6; -.
DR SMR; Q5T1C6; -.
DR BioGRID; 125557; 87.
DR DIP; DIP-60764N; -.
DR IntAct; Q5T1C6; 29.
DR MINT; Q5T1C6; -.
DR STRING; 9606.ENSP00000357804; -.
DR SwissLipids; SLP:000000657; -.
DR iPTMnet; Q5T1C6; -.
DR PhosphoSitePlus; Q5T1C6; -.
DR BioMuta; THEM4; -.
DR DMDM; 74744451; -.
DR EPD; Q5T1C6; -.
DR jPOST; Q5T1C6; -.
DR MassIVE; Q5T1C6; -.
DR MaxQB; Q5T1C6; -.
DR PaxDb; Q5T1C6; -.
DR PeptideAtlas; Q5T1C6; -.
DR PRIDE; Q5T1C6; -.
DR ProteomicsDB; 64259; -.
DR Antibodypedia; 34077; 86 antibodies from 28 providers.
DR DNASU; 117145; -.
DR Ensembl; ENST00000368814.8; ENSP00000357804.3; ENSG00000159445.13.
DR GeneID; 117145; -.
DR KEGG; hsa:117145; -.
DR MANE-Select; ENST00000368814.8; ENSP00000357804.3; NM_053055.5; NP_444283.2.
DR UCSC; uc001ezj.3; human.
DR CTD; 117145; -.
DR DisGeNET; 117145; -.
DR GeneCards; THEM4; -.
DR HGNC; HGNC:17947; THEM4.
DR HPA; ENSG00000159445; Low tissue specificity.
DR MIM; 606388; gene.
DR neXtProt; NX_Q5T1C6; -.
DR OpenTargets; ENSG00000159445; -.
DR PharmGKB; PA142670813; -.
DR VEuPathDB; HostDB:ENSG00000159445; -.
DR eggNOG; KOG4781; Eukaryota.
DR GeneTree; ENSGT00940000160047; -.
DR HOGENOM; CLU_072603_0_1_1; -.
DR InParanoid; Q5T1C6; -.
DR OMA; MFYNDVE; -.
DR OrthoDB; 1322443at2759; -.
DR PhylomeDB; Q5T1C6; -.
DR TreeFam; TF332518; -.
DR BRENDA; 3.1.2.20; 2681.
DR PathwayCommons; Q5T1C6; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-165158; Activation of AKT2.
DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR SABIO-RK; Q5T1C6; -.
DR SignaLink; Q5T1C6; -.
DR SIGNOR; Q5T1C6; -.
DR BioGRID-ORCS; 117145; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; THEM4; human.
DR GenomeRNAi; 117145; -.
DR Pharos; Q5T1C6; Tbio.
DR PRO; PR:Q5T1C6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T1C6; protein.
DR Bgee; ENSG00000159445; Expressed in kidney epithelium and 182 other tissues.
DR ExpressionAtlas; Q5T1C6; baseline and differential.
DR Genevisible; Q5T1C6; HS.
DR GO; GO:0005829; C:cytosol; IDA: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:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:1902108; P:regulation of mitochondrial membrane permeability involved in apoptotic process; IMP: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 3D-structure; Acetylation; Apoptosis; Cell membrane; Cell projection;
KW Cytoplasm; Fatty acid metabolism; Hydrolase; Lipid metabolism; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 37..240
FT /note="Acyl-coenzyme A thioesterase THEM4"
FT /id="PRO_0000314179"
FT ACT_SITE 161
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:22871024"
FT BINDING 183
FT /ligand="substrate"
FT BINDING 185
FT /ligand="substrate"
FT BINDING 206..207
FT /ligand="substrate"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19604401"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19604401"
FT MOD_RES 55
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 66
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 74
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 98
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 207
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT VARIANT 17
FT /note="L -> R (in dbSNP:rs3748805)"
FT /evidence="ECO:0000269|PubMed:11598301,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17013611, ECO:0000269|Ref.4"
FT /id="VAR_037865"
FT VARIANT 38
FT /note="S -> C (in dbSNP:rs144257719)"
FT /evidence="ECO:0000269|PubMed:17013611"
FT /id="VAR_037866"
FT MUTAGEN 37..38
FT /note="SS->DD: Abolishes import into the mitochondria."
FT /evidence="ECO:0000269|PubMed:19604401"
FT MUTAGEN 37
FT /note="S->A: Abolishes cleavage of mitochondrial transit
FT peptide."
FT /evidence="ECO:0000269|PubMed:19168129"
FT MUTAGEN 152
FT /note="H->A,F: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:22871024"
FT MUTAGEN 161
FT /note="D->E,N: Nearly abolishes enzyme activity. Strongly
FT reduced affinity for myristoyl-CoA."
FT /evidence="ECO:0000269|PubMed:22871024"
FT MUTAGEN 177
FT /note="T->A: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:22871024"
FT MUTAGEN 183
FT /note="N->A: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:22871024"
FT MUTAGEN 206
FT /note="R->A: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:22871024"
FT MUTAGEN 207
FT /note="K->A: Slightly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:22871024"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:4AE8"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:4AE8"
FT HELIX 84..93
FT /evidence="ECO:0007829|PDB:4GAH"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:4AE8"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:4AE8"
FT TURN 129..132
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 133..140
FT /evidence="ECO:0007829|PDB:4AE8"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4AE8"
FT HELIX 153..172
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 175..184
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 193..204
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 207..216
FT /evidence="ECO:0007829|PDB:4AE8"
FT STRAND 222..232
FT /evidence="ECO:0007829|PDB:4AE8"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:4GAH"
SQ SEQUENCE 240 AA; 27130 MW; A01071B07A1B5FB2 CRC64;
MLRSCAARLR TLGALCLPPV GRRLPGSEPR PELRSFSSEE VILKDCSVPN PSWNKDLRLL
FDQFMKKCED GSWKRLPSYK RTPTEWIQDF KTHFLDPKLM KEEQMSQAQL FTRSFDDGLG
FEYVMFYNDI EKRMVCLFQG GPYLEGPPGF IHGGAIATMI DATVGMCAMM AGGIVMTANL
NINYKRPIPL CSVVMINSQL DKVEGRKFFV SCNVQSVDEK TLYSEATSLF IKLNPAKSLT
