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Protein

Acyl-coenzyme A thioesterase THEM4

Gene

THEM4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays an role in mitochondrial fatty acid metabolism. Plays a role in the apoptotic process, possibly via its regulation of AKT1 activity. According to PubMed:11598301, inhibits AKT1 phosphorylation and activity. According to PubMed:17615157, enhances AKT1 activity by favoring its phosphorylation and translocation to plasma membrane.6 Publications

Catalytic activityi

Palmitoyl-CoA + H2O = CoA + palmitate.2 Publications

Kineticsi

  1. KM=2.4 µM for myristoyl-CoA2 Publications
  2. KM=2.6 µM for palmitoyl-CoA2 Publications
  3. KM=5.2 µM for oleoyl-CoA2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei161Proton donor/acceptor1 Publication1
    Binding sitei183Substrate1
    Binding sitei185Substrate1

    GO - Molecular functioni

    GO - Biological processi

    • acyl-CoA metabolic process Source: Reactome
    • fatty acid metabolic process Source: UniProtKB
    • negative regulation of protein kinase B signaling Source: Reactome
    • protein kinase B signaling Source: UniProtKB
    • regulation of mitochondrial membrane permeability involved in apoptotic process Source: UniProtKB

    Keywordsi

    Molecular functionHydrolase
    Biological processApoptosis, Fatty acid metabolism, Lipid metabolism

    Enzyme and pathway databases

    ReactomeiR-HSA-1257604 PIP3 activates AKT signaling
    R-HSA-165158 Activation of AKT2
    R-HSA-199418 Negative regulation of the PI3K/AKT network
    R-HSA-389357 CD28 dependent PI3K/Akt signaling
    R-HSA-5218920 VEGFR2 mediated vascular permeability
    R-HSA-77289 Mitochondrial Fatty Acid Beta-Oxidation
    SIGNORiQ5T1C6

    Chemistry databases

    SwissLipidsiSLP:000000657

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Acyl-coenzyme A thioesterase THEM4 (EC:3.1.2.2)
    Short name:
    Acyl-CoA thioesterase THEM4
    Alternative name(s):
    Carboxyl-terminal modulator protein
    Thioesterase superfamily member 4
    Gene namesi
    Name:THEM4
    Synonyms:CTMP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000159445.12
    HGNCiHGNC:17947 THEM4
    MIMi606388 gene
    neXtProtiNX_Q5T1C6

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi37 – 38SS → DD: Abolishes import into the mitochondria. 1 Publication2
    Mutagenesisi37S → A: Abolishes cleavage of mitochondrial transit peptide. 1 Publication1
    Mutagenesisi152H → A or F: Strongly reduced enzyme activity. 1 Publication1
    Mutagenesisi161D → E or N: Nearly abolishes enzyme activity. Strongly reduced affinity for myristoyl-CoA. 1 Publication1
    Mutagenesisi177T → A: Strongly reduced enzyme activity. 1 Publication1
    Mutagenesisi183N → A: No effect on enzyme activity. 1 Publication1
    Mutagenesisi206R → A: Reduces enzyme activity. 1 Publication1
    Mutagenesisi207K → A: Slightly reduced enzyme activity. 1 Publication1

    Organism-specific databases

    DisGeNETi117145
    OpenTargetsiENSG00000159445
    PharmGKBiPA142670813

    Polymorphism and mutation databases

    BioMutaiTHEM4
    DMDMi74744451

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 36MitochondrionSequence analysisAdd BLAST36
    ChainiPRO_000031417937 – 240Acyl-coenzyme A thioesterase THEM4Add BLAST204

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei37Phosphoserine1 Publication1
    Modified residuei38Phosphoserine1 Publication1
    Modified residuei55N6-succinyllysineBy similarity1
    Modified residuei66N6-succinyllysineBy similarity1
    Modified residuei74N6-acetyllysineBy similarity1
    Modified residuei98N6-succinyllysineBy similarity1
    Modified residuei207N6-succinyllysineBy similarity1

    Post-translational modificationi

    Phosphorylated.2 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ5T1C6
    MaxQBiQ5T1C6
    PaxDbiQ5T1C6
    PeptideAtlasiQ5T1C6
    PRIDEiQ5T1C6
    ProteomicsDBi64259

    PTM databases

    iPTMnetiQ5T1C6
    PhosphoSitePlusiQ5T1C6

    Expressioni

    Tissue specificityi

    Expressed predominantly in skeletal muscle, testis, uterus, brain and kidney. Down-regulated in glioblastoma or glioma compared to non-neoplastic brain due to promoter hypermethylation.2 Publications

    Gene expression databases

    BgeeiENSG00000159445
    CleanExiHS_THEM4
    ExpressionAtlasiQ5T1C6 baseline and differential
    GenevisibleiQ5T1C6 HS

    Organism-specific databases

    HPAiHPA028161

    Interactioni

    Subunit structurei

    Homodimer and homotetramer. Interacts with AKT1 in the cytosol.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AKT1P317494EBI-7684443,EBI-296087

    Protein-protein interaction databases

    BioGridi125557, 18 interactors
    DIPiDIP-60764N
    IntActiQ5T1C6, 6 interactors
    MINTiQ5T1C6
    STRINGi9606.ENSP00000357804

    Structurei

    Secondary structure

    1240
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi55 – 67Combined sources13
    Turni68 – 70Combined sources3
    Beta strandi71 – 76Combined sources6
    Helixi84 – 93Combined sources10
    Helixi111 – 113Combined sources3
    Turni117 – 119Combined sources3
    Beta strandi120 – 128Combined sources9
    Turni129 – 132Combined sources4
    Beta strandi133 – 140Combined sources8
    Helixi142 – 144Combined sources3
    Beta strandi145 – 147Combined sources3
    Helixi153 – 172Combined sources20
    Beta strandi175 – 184Combined sources10
    Beta strandi193 – 204Combined sources12
    Beta strandi207 – 216Combined sources10
    Beta strandi222 – 232Combined sources11
    Turni235 – 237Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4AE8X-ray1.59A/B/C/D37-240[»]
    4GAHX-ray2.30A/B40-240[»]
    ProteinModelPortaliQ5T1C6
    SMRiQ5T1C6
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni206 – 207Substrate binding2

    Sequence similaritiesi

    Belongs to the THEM4/THEM5 thioesterase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiKOG4781 Eukaryota
    ENOG4111ZF6 LUCA
    GeneTreeiENSGT00390000018826
    HOGENOMiHOG000220857
    HOVERGENiHBG054340
    InParanoidiQ5T1C6
    KOiK16339
    OMAiRKFFVSC
    OrthoDBiEOG091G0G1S
    PhylomeDBiQ5T1C6
    TreeFamiTF332518

    Family and domain databases

    InterProiView protein in InterPro
    IPR029069 HotDog_dom_sf
    IPR006683 Thioestr_dom
    PfamiView protein in Pfam
    PF03061 4HBT, 1 hit
    SUPFAMiSSF54637 SSF54637, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q5T1C6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLRSCAARLR TLGALCLPPV GRRLPGSEPR PELRSFSSEE VILKDCSVPN
    60 70 80 90 100
    PSWNKDLRLL FDQFMKKCED GSWKRLPSYK RTPTEWIQDF KTHFLDPKLM
    110 120 130 140 150
    KEEQMSQAQL FTRSFDDGLG FEYVMFYNDI EKRMVCLFQG GPYLEGPPGF
    160 170 180 190 200
    IHGGAIATMI DATVGMCAMM AGGIVMTANL NINYKRPIPL CSVVMINSQL
    210 220 230 240
    DKVEGRKFFV SCNVQSVDEK TLYSEATSLF IKLNPAKSLT
    Length:240
    Mass (Da):27,130
    Last modified:December 21, 2004 - v1
    Checksum:iA01071B07A1B5FB2
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03786517L → R5 PublicationsCorresponds to variant dbSNP:rs3748805Ensembl.1
    Natural variantiVAR_03786638S → C1 PublicationCorresponds to variant dbSNP:rs144257719Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ313515 mRNA Translation: CAC86384.1
    AK314852 mRNA Translation: BAG37369.1
    AL450992 Genomic DNA No translation available.
    CH471121 Genomic DNA Translation: EAW53400.1
    BC065277 mRNA Translation: AAH65277.1
    CCDSiCCDS1006.1
    RefSeqiNP_444283.2, NM_053055.4
    UniGeneiHs.164070

    Genome annotation databases

    EnsembliENST00000368814; ENSP00000357804; ENSG00000159445
    GeneIDi117145
    KEGGihsa:117145
    UCSCiuc001ezj.3 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiTHEM4_HUMAN
    AccessioniPrimary (citable) accession number: Q5T1C6
    Secondary accession number(s): B2RBX2, Q96KR2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: December 21, 2004
    Last modified: June 20, 2018
    This is version 122 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

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