THEM4_RAT
ID THEM4_RAT Reviewed; 230 AA.
AC Q566R0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 95.
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=Thioesterase superfamily member 4;
DE Flags: Precursor;
GN Name=Them4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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).
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 (By
CC similarity). {ECO:0000250|UniProtKB:Q5T1C6}.
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 (By similarity). {ECO:0000250|UniProtKB:Q5T1C6}.
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:0000250|UniProtKB:Q5T1C6}. 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 -!- SIMILARITY: Belongs to the THEM4/THEM5 thioesterase family.
CC {ECO:0000305}.
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DR EMBL; BC093385; AAH93385.1; -; mRNA.
DR RefSeq; NP_001020188.1; NM_001025017.1.
DR AlphaFoldDB; Q566R0; -.
DR SMR; Q566R0; -.
DR STRING; 10116.ENSRNOP00000028260; -.
DR iPTMnet; Q566R0; -.
DR PhosphoSitePlus; Q566R0; -.
DR PaxDb; Q566R0; -.
DR PRIDE; Q566R0; -.
DR Ensembl; ENSRNOT00000028260; ENSRNOP00000028260; ENSRNOG00000020829.
DR GeneID; 361992; -.
DR KEGG; rno:361992; -.
DR UCSC; RGD:1304723; rat.
DR CTD; 117145; -.
DR RGD; 1304723; Them4.
DR eggNOG; KOG4781; Eukaryota.
DR GeneTree; ENSGT00940000160047; -.
DR HOGENOM; CLU_072603_0_1_1; -.
DR InParanoid; Q566R0; -.
DR OMA; MFYNDVE; -.
DR OrthoDB; 1322443at2759; -.
DR PhylomeDB; Q566R0; -.
DR TreeFam; TF332518; -.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-165158; Activation of AKT2.
DR Reactome; R-RNO-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-RNO-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-RNO-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR PRO; PR:Q566R0; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000020829; Expressed in heart and 20 other tissues.
DR Genevisible; Q566R0; RN.
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; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Apoptosis; Cell membrane; Cell projection; Cytoplasm;
KW Fatty acid metabolism; Hydrolase; Lipid metabolism; Membrane;
KW 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_0000314181"
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:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 57
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 65
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 89
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 98
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
FT MOD_RES 197
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UUI3"
SQ SEQUENCE 230 AA; 26089 MW; 08840291C025B9A5 CRC64;
MLRSCAMRLR TLGATPARRP EATRRLFSSE EVVCKDYALP NPSWTKDLRL LFDQFMKKCE
DGSWKRLPSY RQNPPQALQE FQTHFVDSKF KKEEQMSKAQ QFTRSLEEGL GFEYAMFYNK
AEKRIVCLFQ GGLHLQGMPG FVHGGAIATI IDITAGMCAF SEGIVMTANL NIDYKKPIPL
LSVVVVNSQL QKIEGRKLFV SCTIQSTDEK TLHTQATALF IKLDPDKPLT
