P28330 · ACADL_HUMAN
- ProteinLong-chain specific acyl-CoA dehydrogenase, mitochondrial
- GeneACADL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids430 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (By similarity).
The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (By similarity).
Among the different mitochondrial acyl-CoA dehydrogenases, long-chain specific acyl-CoA dehydrogenase can act on saturated and unsaturated acyl-CoAs with 6 to 24 carbons with a preference for 8 to 18 carbons long primary chains (PubMed:21237683, PubMed:8823175).
The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (By similarity).
Among the different mitochondrial acyl-CoA dehydrogenases, long-chain specific acyl-CoA dehydrogenase can act on saturated and unsaturated acyl-CoAs with 6 to 24 carbons with a preference for 8 to 18 carbons long primary chains (PubMed:21237683, PubMed:8823175).
Catalytic activity
- a long-chain 2,3-saturated fatty acyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + hexanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-hexenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + octanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-octenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- decanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-decenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- dodecanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-dodecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + oxidized [electron-transfer flavoprotein] + tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + hexadecanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- eicosanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- docosanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-docosenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + oxidized [electron-transfer flavoprotein] + tetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- (5E)-tetradecenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,5E)-tetradecadienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- (5Z)-tetradecenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,5Z)-tetradecadienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
29 μM | hexanoyl-CoA | |||||
8 μM | octanoyl-CoA | |||||
10 μM | decanoyl-CoA | |||||
7 μM | dodecanoyl-CoA | |||||
10 μM | tetradecanoyl-CoA | |||||
14 μM | hexadecanoyl-CoA | |||||
8 μM | octadecanoyl-CoA |
Pathway
Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 170-179 | FAD (UniProtKB | ChEBI) | ||||
Sequence: IAMTEPGAGS | ||||||
Binding site | 179 | substrate | ||||
Sequence: S | ||||||
Binding site | 203-205 | FAD (UniProtKB | ChEBI) | ||||
Sequence: FIS | ||||||
Binding site | 227-228 | substrate | ||||
Sequence: AH | ||||||
Binding site | 282 | substrate | ||||
Sequence: Y | ||||||
Binding site | 289-292 | substrate | ||||
Sequence: PQER | ||||||
Active site | 291 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 317 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 328 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 385-389 | FAD (UniProtKB | ChEBI) | ||||
Sequence: QLHGG | ||||||
Binding site | 412-413 | substrate | ||||
Sequence: GG | ||||||
Binding site | 414-416 | FAD (UniProtKB | ChEBI) | ||||
Sequence: TNE |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrial membrane | |
Cellular Component | mitochondrion | |
Molecular Function | fatty-acyl-CoA binding | |
Molecular Function | flavin adenine dinucleotide binding | |
Molecular Function | identical protein binding | |
Molecular Function | long-chain fatty acyl-CoA dehydrogenase activity | |
Molecular Function | palmitoyl-CoA oxidase activity | |
Biological Process | carnitine catabolic process | |
Biological Process | carnitine metabolic process, CoA-linked | |
Biological Process | cellular lipid catabolic process | |
Biological Process | fatty acid beta-oxidation using acyl-CoA dehydrogenase | |
Biological Process | long-chain fatty acid catabolic process | |
Biological Process | negative regulation of fatty acid biosynthetic process | |
Biological Process | negative regulation of fatty acid oxidation | |
Biological Process | positive regulation of cold-induced thermogenesis | |
Biological Process | regulation of cholesterol metabolic process | |
Biological Process | temperature homeostasis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameLong-chain specific acyl-CoA dehydrogenase, mitochondrial
- EC number
- Short namesLCAD
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP28330
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 291 | Loss of long-chain-acyl-CoA dehydrogenase activity. No effect on protein abundance. No effect on solubility. No effect on substrate binding. | ||||
Sequence: E → Q | ||||||
Natural variant | VAR_000328 | 303 | in dbSNP:rs1801204 | |||
Sequence: S → T | ||||||
Natural variant | VAR_000329 | 333 | in dbSNP:rs2286963 | |||
Sequence: K → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 490 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, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-30 | Mitochondrion | ||||
Sequence: MAARLLRGSLRVLGGHRAPRQLPAARCSHS | ||||||
Chain | PRO_0000000509 | 31-430 | Long-chain specific acyl-CoA dehydrogenase, mitochondrial | |||
Sequence: GGEERLETPSAKKLTDIGIRRIFSPEHDIFRKSVRKFFQEEVIPHHSEWEKAGEVSREVWEKAGKQGLLGVNIAEHLGGIGGDLYSAAIVWEEQAYSNCSGPGFSIHSGIVMSYITNHGSEEQIKHFIPQMTAGKCIGAIAMTEPGAGSDLQGIKTNAKKDGSDWILNGSKVFISNGSLSDVVIVVAVTNHEAPSPAHGISLFLVENGMKGFIKGRKLHKMGLKAQDTAELFFEDIRLPASALLGEENKGFYYIMKELPQERLLIADVAISASEFMFEETRNYVKQRKAFGKTVAHLQTVQHKLAELKTHICVTRAFVDNCLQLHEAKRLDSATACMAKYWASELQNSVAYDCVQLHGGWGYMWEYPIAKAYVDARVQPIYGGTNEIMKELIAREIVFDK | ||||||
Modified residue | 42 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 54 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 66 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 66 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 81 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 81 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 92 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 95 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 165 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 240 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 254 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 254 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 279 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 279 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 318 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 322 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 322 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 358 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 362 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Acetylation at Lys-318 and Lys-322 in proximity of the cofactor-binding sites strongly reduces catalytic activity. These sites are deacetylated by SIRT3.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homotetramer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P28330 | SYT2 Q8N9I0 | 2 | EBI-12059321, EBI-8032987 | |
BINARY | P28330 | TGM1 P22735 | 3 | EBI-12059321, EBI-2562368 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length430
- Mass (Da)47,656
- Last updated2009-02-10 v2
- Checksum72F9803685406DF9
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M74096 EMBL· GenBank· DDBJ | AAA51565.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313498 EMBL· GenBank· DDBJ | BAG36280.1 EMBL· GenBank· DDBJ | mRNA | ||
AC006994 EMBL· GenBank· DDBJ | AAY14881.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471063 EMBL· GenBank· DDBJ | EAW70481.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC039063 EMBL· GenBank· DDBJ | AAH39063.1 EMBL· GenBank· DDBJ | mRNA | ||
BC064549 EMBL· GenBank· DDBJ | AAH64549.1 EMBL· GenBank· DDBJ | mRNA |