Q5T1C6 · THEM4_HUMAN
- ProteinAcyl-coenzyme A thioesterase THEM4
- GeneTHEM4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids240 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
Catalytic activity
- H2O + hexadecanoyl-CoA = CoA + H+ + hexadecanoateThis reaction proceeds in the forward direction.
- H2O + octanoyl-CoA = CoA + H+ + octanoateThis reaction proceeds in the forward direction.
- decanoyl-CoA + H2O = CoA + decanoate + H+This reaction proceeds in the forward direction.
- dodecanoyl-CoA + H2O = CoA + dodecanoate + H+This reaction proceeds in the forward direction.
- H2O + tetradecanoyl-CoA = CoA + H+ + tetradecanoateThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H+This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA + H+This reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.4 μM | myristoyl-CoA | |||||
2.6 μM | palmitoyl-CoA | |||||
5.2 μM | oleoyl-CoA |
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 161 | Proton donor/acceptor | ||||
Sequence: D | ||||||
Binding site | 183 | substrate | ||||
Sequence: N | ||||||
Binding site | 185 | substrate | ||||
Sequence: K | ||||||
Binding site | 206-207 | substrate | ||||
Sequence: RK |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial intermembrane space | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Cellular Component | plasma membrane | |
Cellular Component | ruffle membrane | |
Molecular Function | long-chain fatty acyl-CoA hydrolase activity | |
Biological Process | fatty acid metabolic process | |
Biological Process | negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | regulation of mitochondrial membrane permeability involved in apoptotic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameAcyl-coenzyme A thioesterase THEM4
- EC number
- Short namesAcyl-CoA thioesterase THEM4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ5T1C6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Peripheral membrane protein
Note: Released from the mitochondria into the cytosol in response to apoptotic stimuli.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_037865 | 17 | in dbSNP:rs3748805 | |||
Sequence: L → R | ||||||
Mutagenesis | 37 | Abolishes cleavage of mitochondrial transit peptide. | ||||
Sequence: S → A | ||||||
Mutagenesis | 37-38 | Abolishes import into the mitochondria. | ||||
Sequence: SS → DD | ||||||
Natural variant | VAR_037866 | 38 | in dbSNP:rs144257719 | |||
Sequence: S → C | ||||||
Mutagenesis | 152 | Strongly reduced enzyme activity. | ||||
Sequence: H → A or F | ||||||
Mutagenesis | 161 | Nearly abolishes enzyme activity. Strongly reduced affinity for myristoyl-CoA. | ||||
Sequence: D → E or N | ||||||
Mutagenesis | 177 | Strongly reduced enzyme activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 183 | No effect on enzyme activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 206 | Reduces enzyme activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 207 | Slightly reduced enzyme activity. | ||||
Sequence: K → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 298 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-36 | Mitochondrion | ||||
Sequence: MLRSCAARLRTLGALCLPPVGRRLPGSEPRPELRSF | ||||||
Modified residue | 37 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000314179 | 37-240 | Acyl-coenzyme A thioesterase THEM4 | |||
Sequence: SSEEVILKDCSVPNPSWNKDLRLLFDQFMKKCEDGSWKRLPSYKRTPTEWIQDFKTHFLDPKLMKEEQMSQAQLFTRSFDDGLGFEYVMFYNDIEKRMVCLFQGGPYLEGPPGFIHGGAIATMIDATVGMCAMMAGGIVMTANLNINYKRPIPLCSVVMINSQLDKVEGRKFFVSCNVQSVDEKTLYSEATSLFIKLNPAKSLT | ||||||
Modified residue | 38 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 55 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 66 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 74 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 98 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 207 | N6-succinyllysine | ||||
Sequence: K |
Post-translational modification
Phosphorylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer and homotetramer. Interacts with AKT1 in the cytosol.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q5T1C6 | AKT1 P31749 | 4 | EBI-7684443, EBI-296087 | |
BINARY | Q5T1C6 | FGFR3 P22607 | 3 | EBI-7684443, EBI-348399 | |
BINARY | Q5T1C6 | HRAS P01112 | 3 | EBI-7684443, EBI-350145 | |
BINARY | Q5T1C6 | PECAM1 P16284 | 3 | EBI-7684443, EBI-716404 | |
BINARY | Q5T1C6 | Q9Y649 | 3 | EBI-7684443, EBI-25900580 | |
BINARY | Q5T1C6 | SPRED1 Q7Z699 | 3 | EBI-7684443, EBI-5235340 | |
BINARY | Q5T1C6 | VIM P08670 | 3 | EBI-7684443, EBI-353844 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length240
- Mass (Da)27,130
- Last updated2004-12-21 v1
- ChecksumA01071B07A1B5FB2
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ313515 EMBL· GenBank· DDBJ | CAC86384.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314852 EMBL· GenBank· DDBJ | BAG37369.1 EMBL· GenBank· DDBJ | mRNA | ||
AL450992 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471121 EMBL· GenBank· DDBJ | EAW53400.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC065277 EMBL· GenBank· DDBJ | AAH65277.1 EMBL· GenBank· DDBJ | mRNA |