P11310 · ACADM_HUMAN
- ProteinMedium-chain specific acyl-CoA dehydrogenase, mitochondrial
- GeneACADM
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids421 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Medium-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 (PubMed:1970566, PubMed:21237683, PubMed:2251268, 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 (PubMed:2251268).
Electron transfer flavoprotein (ETF) is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:15159392, PubMed:25416781).
Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 6 to 12 carbons long primary chains (PubMed:1970566, PubMed:21237683, PubMed:2251268, 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 (PubMed:2251268).
Electron transfer flavoprotein (ETF) is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:15159392, PubMed:25416781).
Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 6 to 12 carbons long primary chains (PubMed:1970566, PubMed:21237683, PubMed:2251268, PubMed:8823175).
Catalytic activity
- a medium-chain 2,3-saturated fatty acyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = a medium-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + oxidized [electron-transfer flavoprotein] + pentanoyl-CoA = (2E)-pentenoyl-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.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
175 μM | butyryl-CoA | |||||
15 μM | hexanoyl-CoA | |||||
3.4 μM | octanoyl-CoA | |||||
2.5 μM | decanoyl-CoA | |||||
2.5 μM | dodecanoyl-CoA | |||||
2.3 μM | tetradecanoyl-CoA | |||||
1.6 μM | hexadecanoyl-CoA |
Pathway
Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 158-167 | FAD (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: YCVTEPGAGS | ||||||
Binding site | 167 | octanoyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 191-193 | FAD (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: WIT | ||||||
Binding site | 278 | octanoyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 281 | octanoyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 306-308 | FAD (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: RKT | ||||||
Binding site | 316-317 | FAD (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: HQ | ||||||
Binding site | 374-378 | FAD (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: QILGG | ||||||
Active site | 401 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 401 | octanoyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 401-405 | FAD (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: EGTSQ |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameMedium-chain specific acyl-CoA dehydrogenase, mitochondrial
- EC number
- Short namesMCAD
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP11310
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD)
- Note
- DescriptionAn inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy.
- See alsoMIM:201450
Natural variants in ACADMD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_000317 | 53 | R>C | in ACADMD; dbSNP:rs398123072 | |
VAR_013698 | 67 | Y>H | in ACADMD; mild; dbSNP:rs121434280 | |
VAR_015954 | 78 | I>T | in ACADMD; dbSNP:rs398123074 | |
VAR_000318 | 115-116 | missing | in ACADMD | |
VAR_015955 | 116 | C>Y | in ACADMD; dbSNP:rs875989859 | |
VAR_015956 | 121 | T>I | in ACADMD; dbSNP:rs121434283 | |
VAR_000319 | 149 | M>I | in ACADMD; dbSNP:rs121434277 | |
VAR_000320 | 193 | T>A | in ACADMD; the thermostability is markedly decreased; dbSNP:rs121434279 | |
VAR_000321 | 195 | G>R | in ACADMD; dbSNP:rs121434278 | |
VAR_015957 | 206 | R>L | in ACADMD; dbSNP:rs200724875 | |
VAR_000322 | 244 | C>R | in ACADMD; dbSNP:rs121434276 | |
VAR_013699 | 245 | S>L | in ACADMD; dbSNP:rs121434281 | |
VAR_000323 | 267 | G>R | in ACADMD; dbSNP:rs121434274 | |
VAR_013700 | 281 | R>T | in ACADMD; mild clinical phenotype; dbSNP:rs121434282 | |
VAR_015958 | 310 | G>R | in ACADMD; dbSNP:rs747268471 | |
VAR_000324 | 326 | M>T | in ACADMD; dbSNP:rs786204631 | |
VAR_000325 | 329 | K>E | in ACADMD; may alter splicing; decreased fatty acid beta-oxidation; dbSNP:rs77931234 | |
VAR_000326 | 336 | S>R | in ACADMD | |
VAR_015959 | 352 | Y>C | in ACADMD; dbSNP:rs1227800781 | |
VAR_000327 | 375 | I>T | in ACADMD; dbSNP:rs121434275 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_000317 | 53 | in ACADMD; dbSNP:rs398123072 | |||
Sequence: R → C | ||||||
Natural variant | VAR_013698 | 67 | in ACADMD; mild; dbSNP:rs121434280 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_015954 | 78 | in ACADMD; dbSNP:rs398123074 | |||
Sequence: I → T | ||||||
Mutagenesis | 86 | Strongly reduced rate of electron transfer to ETF. | ||||
Sequence: L → M | ||||||
Mutagenesis | 98 | Strongly reduced rate of electron transfer to ETF. | ||||
Sequence: L → W | ||||||
Mutagenesis | 100 | Strongly reduced rate of electron transfer to ETF. | ||||
Sequence: L → Y | ||||||
Mutagenesis | 108 | Strongly reduced rate of electron transfer to ETF. | ||||
Sequence: I → M | ||||||
Natural variant | VAR_000318 | 115-116 | in ACADMD | |||
Sequence: Missing | ||||||
Natural variant | VAR_015955 | 116 | in ACADMD; dbSNP:rs875989859 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_015956 | 121 | in ACADMD; dbSNP:rs121434283 | |||
Sequence: T → I | ||||||
Natural variant | VAR_035716 | 132 | in a breast cancer sample; somatic mutation; dbSNP:rs875989854 | |||
Sequence: P → R | ||||||
Natural variant | VAR_000319 | 149 | in ACADMD; dbSNP:rs121434277 | |||
Sequence: M → I | ||||||
Mutagenesis | 191 | Loss of electron transfer to ETF. | ||||
Sequence: W → A | ||||||
Mutagenesis | 191 | Reduces rate of electron transfer to ETF about six-fold. | ||||
Sequence: W → F | ||||||
Natural variant | VAR_000320 | 193 | in ACADMD; the thermostability is markedly decreased; dbSNP:rs121434279 | |||
Sequence: T → A | ||||||
Natural variant | VAR_000321 | 195 | in ACADMD; dbSNP:rs121434278 | |||
Sequence: G → R | ||||||
Natural variant | VAR_015957 | 206 | in ACADMD; dbSNP:rs200724875 | |||
Sequence: R → L | ||||||
Mutagenesis | 237 | Strongly reduced rate of electron transfer to ETF. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_000322 | 244 | in ACADMD; dbSNP:rs121434276 | |||
Sequence: C → R | ||||||
Natural variant | VAR_013699 | 245 | in ACADMD; dbSNP:rs121434281 | |||
Sequence: S → L | ||||||
Natural variant | VAR_000323 | 267 | in ACADMD; dbSNP:rs121434274 | |||
Sequence: G → R | ||||||
Mutagenesis | 280 | Narrower substrate specificity. Changed substrate specificity towards longer acyl chains; when associated with G-401. Loss of acyl-CoA dehydrogenase activity; when associated with T-410. | ||||
Sequence: T → E | ||||||
Natural variant | VAR_013700 | 281 | in ACADMD; mild clinical phenotype; dbSNP:rs121434282 | |||
Sequence: R → T | ||||||
Natural variant | VAR_015958 | 310 | in ACADMD; dbSNP:rs747268471 | |||
Sequence: G → R | ||||||
Natural variant | VAR_000324 | 326 | in ACADMD; dbSNP:rs786204631 | |||
Sequence: M → T | ||||||
Natural variant | VAR_000325 | 329 | in ACADMD; may alter splicing; decreased fatty acid beta-oxidation; dbSNP:rs77931234 | |||
Sequence: K → E | ||||||
Natural variant | VAR_000326 | 336 | in ACADMD | |||
Sequence: S → R | ||||||
Natural variant | VAR_015959 | 352 | in ACADMD; dbSNP:rs1227800781 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_000327 | 375 | in ACADMD; dbSNP:rs121434275 | |||
Sequence: I → T | ||||||
Mutagenesis | 384 | Reduces rate of electron transfer to ETF three-fold. | ||||
Sequence: E → A | ||||||
Mutagenesis | 384 | Reduces rate of electron transfer to ETF two-fold. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 401 | Changed substrate specificity towards longer acyl chains; when associated with E-280. | ||||
Sequence: E → G | ||||||
Mutagenesis | 401 | Loss of acyl-CoA dehydrogenase activity. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 401 | Loss of acyl-CoA dehydrogenase activity; when associated with E-280. | ||||
Sequence: E → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 710 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-25 | Mitochondrion | ||||
Sequence: MAAGFGRCCRVLRSISRFHWRSQHT | ||||||
Chain | PRO_0000000502 | 26-421 | Medium-chain specific acyl-CoA dehydrogenase, mitochondrial | |||
Sequence: KANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN | ||||||
Modified residue | 69 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 69 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 179 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 212 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 212 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 217 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 217 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 259 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 259 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 271 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 271 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 279 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 301 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 351 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Acetylated. Could occur at proximity of the cofactor-binding sites and reduce the catalytic activity. Could be deacetylated by SIRT3.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Homotetramer (PubMed:8823176, Ref.23). Interacts with the heterodimeric electron transfer flavoprotein ETF.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | PRO_0000000502 | ACADM PRO_0000000502 P11310 | 2 | EBI-44440161, EBI-44440161 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P11310-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length421
- Mass (Da)46,588
- Last updated1989-07-01 v1
- Checksum7CD0B5832410581B
P11310-2
- Name2
- Differences from canonical
- 10-10: R → RCSLQ
Computationally mapped potential isoform sequences
There are 23 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0YDT5 | H0YDT5_HUMAN | ACADM | 67 | ||
A0A7P0T9W7 | A0A7P0T9W7_HUMAN | ACADM | 79 | ||
A0A7P0T8B6 | A0A7P0T8B6_HUMAN | ACADM | 64 | ||
A0A7P0T8G6 | A0A7P0T8G6_HUMAN | ACADM | 335 | ||
A0A7P0T8J9 | A0A7P0T8J9_HUMAN | ACADM | 201 | ||
A0A7P0T932 | A0A7P0T932_HUMAN | ACADM | 374 | ||
Q5T4U5 | Q5T4U5_HUMAN | ACADM | 454 | ||
A0A7P0TAZ5 | A0A7P0TAZ5_HUMAN | ACADM | 52 | ||
A0A7P0TB51 | A0A7P0TB51_HUMAN | ACADM | 342 | ||
A0A7P0TB55 | A0A7P0TB55_HUMAN | ACADM | 275 | ||
A0A7P0TBD1 | A0A7P0TBD1_HUMAN | ACADM | 200 | ||
A0A7P0TBF2 | A0A7P0TBF2_HUMAN | ACADM | 52 | ||
A0A7P0TA39 | A0A7P0TA39_HUMAN | ACADM | 106 | ||
A0A7P0TA63 | A0A7P0TA63_HUMAN | ACADM | 236 | ||
A0A7P0TAB2 | A0A7P0TAB2_HUMAN | ACADM | 199 | ||
A0A7P0TB28 | A0A7P0TB28_HUMAN | ACADM | 74 | ||
E9PRX4 | E9PRX4_HUMAN | ACADM | 76 | ||
E9PQA8 | E9PQA8_HUMAN | ACADM | 45 | ||
E9PLN7 | E9PLN7_HUMAN | ACADM | 50 | ||
E9PIX8 | E9PIX8_HUMAN | ACADM | 47 | ||
E9PJM9 | E9PJM9_HUMAN | ACADM | 104 | ||
A0A7P0Z4Q0 | A0A7P0Z4Q0_HUMAN | ACADM | 43 | ||
F6YB23 | F6YB23_HUMAN | ACADM | 389 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038420 | 10 | in isoform 2 | |||
Sequence: R → RCSLQ | ||||||
Sequence conflict | 356 | in Ref. 3; AAF63626 | ||||
Sequence: I → T |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M16827 EMBL· GenBank· DDBJ | AAA51566.1 EMBL· GenBank· DDBJ | mRNA | ||
M91432 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91421 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91422 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91423 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91425 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91426 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91427 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91428 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91429 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91430 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M91431 EMBL· GenBank· DDBJ | AAA59567.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF251043 EMBL· GenBank· DDBJ | AAF63626.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312629 EMBL· GenBank· DDBJ | BAG35514.1 EMBL· GenBank· DDBJ | mRNA | ||
AL357314 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471059 EMBL· GenBank· DDBJ | EAX06401.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005377 EMBL· GenBank· DDBJ | AAH05377.1 EMBL· GenBank· DDBJ | mRNA | ||
M60505 EMBL· GenBank· DDBJ | AAB59625.1 EMBL· GenBank· DDBJ | Genomic DNA |