UniProtKB - Q5T1C6 (THEM4_HUMAN)
Protein
Acyl-coenzyme A thioesterase THEM4
Gene
THEM4
Organism
Homo sapiens (Human)
Status
Functioni
Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a 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
- EC:3.1.2.22 PublicationsThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=2.4 µM for myristoyl-CoA2 Publications
- KM=2.6 µM for palmitoyl-CoA2 Publications
- KM=5.2 µM for oleoyl-CoA2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 161 | Proton donor/acceptor1 Publication | 1 | |
Binding sitei | 183 | Substrate | 1 | |
Binding sitei | 185 | Substrate | 1 |
GO - Molecular functioni
- myristoyl-CoA hydrolase activity Source: UniProtKB-EC
- palmitoyl-CoA hydrolase activity Source: UniProtKB
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 function | Hydrolase |
Biological process | Apoptosis, Fatty acid metabolism, Lipid metabolism |
Enzyme and pathway databases
PathwayCommonsi | Q5T1C6 |
Reactomei | R-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 |
SABIO-RKi | Q5T1C6 |
SIGNORi | Q5T1C6 |
Chemistry databases
SwissLipidsi | SLP:000000657 |
Names & Taxonomyi
Protein namesi | Recommended name: Acyl-coenzyme A thioesterase THEM4 (EC:3.1.2.22 Publications)Short name: Acyl-CoA thioesterase THEM4 Alternative name(s): Carboxyl-terminal modulator protein Thioesterase superfamily member 4 |
Gene namesi | Name:THEM4 Synonyms:CTMP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17947, THEM4 |
MIMi | 606388, gene |
neXtProti | NX_Q5T1C6 |
VEuPathDBi | HostDB:ENSG00000159445.12 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
- ruffle membrane 1 Publication
Mitochondrion
- Mitochondrion 3 Publications
- Mitochondrion inner membrane ; Peripheral membrane protein 1 Publication
- Mitochondrion intermembrane space 2 Publications
Other locations
- Cytoplasm 1 Publication
Note: Released from the mitochondria into the cytosol in response to apoptotic stimuli.1 Publication
Cytosol
- cytosol Source: UniProtKB
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB-SubCell
- mitochondrial intermembrane space Source: UniProtKB-SubCell
- mitochondrial matrix Source: Reactome
- mitochondrion Source: UniProtKB
Plasma Membrane
- plasma membrane Source: Reactome
- ruffle membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 37 – 38 | SS → DD: Abolishes import into the mitochondria. 1 Publication | 2 | |
Mutagenesisi | 37 | S → A: Abolishes cleavage of mitochondrial transit peptide. 1 Publication | 1 | |
Mutagenesisi | 152 | H → A or F: Strongly reduced enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 161 | D → E or N: Nearly abolishes enzyme activity. Strongly reduced affinity for myristoyl-CoA. 1 Publication | 1 | |
Mutagenesisi | 177 | T → A: Strongly reduced enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 183 | N → A: No effect on enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 206 | R → A: Reduces enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 207 | K → A: Slightly reduced enzyme activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 117145 |
OpenTargetsi | ENSG00000159445 |
PharmGKBi | PA142670813 |
Miscellaneous databases
Pharosi | Q5T1C6, Tbio |
Genetic variation databases
BioMutai | THEM4 |
DMDMi | 74744451 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 36 | MitochondrionSequence analysisAdd BLAST | 36 | |
ChainiPRO_0000314179 | 37 – 240 | Acyl-coenzyme A thioesterase THEM4Add BLAST | 204 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 37 | Phosphoserine1 Publication | 1 | |
Modified residuei | 38 | Phosphoserine1 Publication | 1 | |
Modified residuei | 55 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 66 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 74 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 98 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 207 | N6-succinyllysineBy similarity | 1 |
Post-translational modificationi
Phosphorylated.2 Publications
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q5T1C6 |
jPOSTi | Q5T1C6 |
MassIVEi | Q5T1C6 |
MaxQBi | Q5T1C6 |
PaxDbi | Q5T1C6 |
PeptideAtlasi | Q5T1C6 |
PRIDEi | Q5T1C6 |
ProteomicsDBi | 64259 |
PTM databases
iPTMneti | Q5T1C6 |
PhosphoSitePlusi | Q5T1C6 |
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
Bgeei | ENSG00000159445, Expressed in amniotic fluid and 215 other tissues |
ExpressionAtlasi | Q5T1C6, baseline and differential |
Genevisiblei | Q5T1C6, HS |
Organism-specific databases
HPAi | ENSG00000159445, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer and homotetramer.
Interacts with AKT1 in the cytosol.
3 PublicationsBinary interactionsi
Hide detailsQ5T1C6
Protein-protein interaction databases
BioGRIDi | 125557, 39 interactors |
DIPi | DIP-60764N |
IntActi | Q5T1C6, 26 interactors |
MINTi | Q5T1C6 |
STRINGi | 9606.ENSP00000357804 |
Miscellaneous databases
RNActi | Q5T1C6, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q5T1C6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 206 – 207 | Substrate binding | 2 |
Sequence similaritiesi
Belongs to the THEM4/THEM5 thioesterase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG4781, Eukaryota |
GeneTreei | ENSGT00940000160047 |
HOGENOMi | CLU_072603_0_1_1 |
InParanoidi | Q5T1C6 |
OMAi | CIFQAGH |
OrthoDBi | 1322443at2759 |
PhylomeDBi | Q5T1C6 |
TreeFami | TF332518 |
Family and domain databases
InterProi | View protein in InterPro IPR029069, HotDog_dom_sf IPR006683, Thioestr_dom |
Pfami | View protein in Pfam PF03061, 4HBT, 1 hit |
SUPFAMi | SSF54637, SSF54637, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
Q5T1C6-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PLJ7 | E9PLJ7_HUMAN | Acyl-coenzyme A thioesterase THEM4 | THEM4 | 110 | Annotation score: | ||
F6XC58 | F6XC58_HUMAN | Acyl-coenzyme A thioesterase THEM4 | THEM4 | 107 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_037865 | 17 | L → R5 PublicationsCorresponds to variant dbSNP:rs3748805Ensembl. | 1 | |
Natural variantiVAR_037866 | 38 | S → 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 |
CCDSi | CCDS1006.1 |
RefSeqi | NP_444283.2, NM_053055.4 |
Genome annotation databases
Ensembli | ENST00000368814; ENSP00000357804; ENSG00000159445 |
GeneIDi | 117145 |
KEGGi | hsa:117145 |
UCSCi | uc001ezj.3, human |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS1006.1 |
RefSeqi | NP_444283.2, NM_053055.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4AE8 | X-ray | 1.59 | A/B/C/D | 37-240 | [»] | |
4GAH | X-ray | 2.30 | A/B | 40-240 | [»] | |
SMRi | Q5T1C6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 125557, 39 interactors |
DIPi | DIP-60764N |
IntActi | Q5T1C6, 26 interactors |
MINTi | Q5T1C6 |
STRINGi | 9606.ENSP00000357804 |
Chemistry databases
SwissLipidsi | SLP:000000657 |
PTM databases
iPTMneti | Q5T1C6 |
PhosphoSitePlusi | Q5T1C6 |
Genetic variation databases
BioMutai | THEM4 |
DMDMi | 74744451 |
Proteomic databases
EPDi | Q5T1C6 |
jPOSTi | Q5T1C6 |
MassIVEi | Q5T1C6 |
MaxQBi | Q5T1C6 |
PaxDbi | Q5T1C6 |
PeptideAtlasi | Q5T1C6 |
PRIDEi | Q5T1C6 |
ProteomicsDBi | 64259 |
Protocols and materials databases
Antibodypediai | 34077, 80 antibodies |
Genome annotation databases
Ensembli | ENST00000368814; ENSP00000357804; ENSG00000159445 |
GeneIDi | 117145 |
KEGGi | hsa:117145 |
UCSCi | uc001ezj.3, human |
Organism-specific databases
CTDi | 117145 |
DisGeNETi | 117145 |
GeneCardsi | THEM4 |
HGNCi | HGNC:17947, THEM4 |
HPAi | ENSG00000159445, Low tissue specificity |
MIMi | 606388, gene |
neXtProti | NX_Q5T1C6 |
OpenTargetsi | ENSG00000159445 |
PharmGKBi | PA142670813 |
VEuPathDBi | HostDB:ENSG00000159445.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4781, Eukaryota |
GeneTreei | ENSGT00940000160047 |
HOGENOMi | CLU_072603_0_1_1 |
InParanoidi | Q5T1C6 |
OMAi | CIFQAGH |
OrthoDBi | 1322443at2759 |
PhylomeDBi | Q5T1C6 |
TreeFami | TF332518 |
Enzyme and pathway databases
PathwayCommonsi | Q5T1C6 |
Reactomei | R-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 |
SABIO-RKi | Q5T1C6 |
SIGNORi | Q5T1C6 |
Miscellaneous databases
BioGRID-ORCSi | 117145, 9 hits in 876 CRISPR screens |
ChiTaRSi | THEM4, human |
GenomeRNAii | 117145 |
Pharosi | Q5T1C6, Tbio |
PROi | PR:Q5T1C6 |
RNActi | Q5T1C6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000159445, Expressed in amniotic fluid and 215 other tissues |
ExpressionAtlasi | Q5T1C6, baseline and differential |
Genevisiblei | Q5T1C6, HS |
Family and domain databases
InterProi | View protein in InterPro IPR029069, HotDog_dom_sf IPR006683, Thioestr_dom |
Pfami | View protein in Pfam PF03061, 4HBT, 1 hit |
SUPFAMi | SSF54637, SSF54637, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | THEM4_HUMAN | |
Accessioni | Q5T1C6Primary (citable) accession number: Q5T1C6 Secondary accession number(s): B2RBX2, Q96KR2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 15, 2008 |
Last sequence update: | December 21, 2004 | |
Last modified: | February 10, 2021 | |
This is version 139 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants