P11182 · ODB2_HUMAN
- ProteinLipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial
- GeneDBT
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids482 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO2. It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component.
Catalytic activity
- 2-methylpropanoyl-CoA + N6-[(R)-dihydrolipoyl]-L-lysyl-[protein] = CoA + N6-[(R)-S8-2-methylpropanoyldihydrolipoyl]-L-lysyl-[protein]This reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 lipoyl cofactor covalently.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 291 | CoA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 306 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 349 | CoA (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 378 | CoA (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 399 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 400 | CoA (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 403 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 424 | CoA (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 426 | CoA (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Active site | 452 | |||||
Sequence: H | ||||||
Active site | 456 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | branched-chain alpha-ketoacid dehydrogenase complex | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | microtubule cytoskeleton | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrial nucleoid | |
Cellular Component | mitochondrion | |
Cellular Component | oxoglutarate dehydrogenase complex | |
Molecular Function | acetyltransferase activity | |
Molecular Function | dihydrolipoyllysine-residue (2-methylpropanoyl)transferase activity | |
Molecular Function | lipoic acid binding | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | branched-chain amino acid catabolic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP11182
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Maple syrup urine disease 2 (MSUD2)
- Note
- DescriptionA form of maple syrup urine disease, an autosomal recessive metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
- See alsoMIM:620699
Natural variants in MSUD2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_015099 | 98 | I>M | in MSUD2; dbSNP:rs121965001 | |
VAR_004978 | 276 | F>C | in MSUD2; dbSNP:rs121964999 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_015099 | 98 | in MSUD2; dbSNP:rs121965001 | |||
Sequence: I → M | ||||||
Mutagenesis | 105 | Abolishes lipoylation but retains normal interaction with PPM1K. | ||||
Sequence: K → A | ||||||
Mutagenesis | 147 | Has no effect on the interaction with PPM1K. | ||||
Sequence: E → A | ||||||
Mutagenesis | 148 | Completely abolishes the interaction with PPM1K. | ||||
Sequence: E → A | ||||||
Mutagenesis | 149 | Completely abolishes the interaction with PPM1K. | ||||
Sequence: D → A | ||||||
Mutagenesis | 152 | Has no effect on the interaction with PPM1K. | ||||
Sequence: E → A | ||||||
Mutagenesis | 159 | Has no effect on the interaction with PPM1K. | ||||
Sequence: D → A | ||||||
Natural variant | VAR_004978 | 276 | in MSUD2; dbSNP:rs121964999 | |||
Sequence: F → C | ||||||
Natural variant | VAR_015100 | 384 | in dbSNP:rs12021720 | |||
Sequence: S → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 574 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-61 | UniProt | Mitochondrion | ||||
Sequence: MAAVRMLRTWSRNAGKLICVRYFQTCGNVHVLKPNYVCFFGYPSFKYSHPHHFLKTTAALR | |||||||
Chain | PRO_0000020489 | 62-482 | UniProt | Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial | |||
Sequence: GQVVQFKLSDIGEGIREVTVKEWYVKEGDTVSQFDSICEVQSDKASVTITSRYDGVIKKLYYNLDDIAYVGKPLVDIETEALKDSEEDVVETPAVSHDEHTHQEIKGRKTLATPAVRRLAMENNIKLSEVVGSGKDGRILKEDILNYLEKQTGAILPPSPKVEIMPPPPKPKDMTVPILVSKPPVFTGKDKTEPIKGFQKAMVKTMSAALKIPHFGYCDEIDLTELVKLREELKPIAFARGIKLSFMPFFLKAASLGLLQFPILNASVDENCQNITYKASHNIGIAMDTEQGLIVPNVKNVQICSIFDIATELNRLQKLGSVSQLSTTDLTGGTFTLSNIGSIGGTFAKPVIMPPEVAIGALGSIKAIPRFNQKGEVYKAQIMNVSWSADHRVIDGATMSRFSNLWKSYLENPAFMLLDLK | |||||||
Modified residue | 105 | UniProt | N6-lipoyllysine | ||||
Sequence: K | |||||||
Modified residue | 133 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue | 196 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 196 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 202 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 220 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 220 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 243 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 250 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 261 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue | 289 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 289 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 295 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 304 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 435 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 440 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 440 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Forms a 24-polypeptide structural core with octahedral symmetry that represents the E2 component of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. The BCKDH complex is composed of three major building blocks E1, E2 and E3. It is organized around E2, a 24-meric cubic core composed of DBT, to which are associated 6 to 12 copies of E1, and approximately 6 copies of the dehydrogenase E3, a DLD dimer (By similarity) (PubMed:22291014).
Interacts with PPM1K with a 24:1 stoichiometry; the N-terminal region (residues 49-61) of PPM1K and C-terminal linker of the lipoyl domain of DBT/E2 (residues 145-160) are critical for this interaction whereas the lipoyl prosthetic group is dispensable. This interaction requires colocalization in mitochondria (PubMed:19411760, PubMed:22291014, PubMed:22589535).
PPM1K competes with BCKDK for binding to DBT; this interaction is modulated by branched-chain alpha-keto acids (BCKAs). At steady state, BCKDH holoenzyme preferentially binds BCKDK and BCKDHA is phosphorylated. In response to high levels of BCKAs, BCKDK is replaced by PPM1K leading to BCKDHA dephosphorylation (PubMed:22589535, PubMed:37558654).
Interacts with PPM1K with a 24:1 stoichiometry; the N-terminal region (residues 49-61) of PPM1K and C-terminal linker of the lipoyl domain of DBT/E2 (residues 145-160) are critical for this interaction whereas the lipoyl prosthetic group is dispensable. This interaction requires colocalization in mitochondria (PubMed:19411760, PubMed:22291014, PubMed:22589535).
PPM1K competes with BCKDK for binding to DBT; this interaction is modulated by branched-chain alpha-keto acids (BCKAs). At steady state, BCKDH holoenzyme preferentially binds BCKDK and BCKDHA is phosphorylated. In response to high levels of BCKAs, BCKDK is replaced by PPM1K leading to BCKDHA dephosphorylation (PubMed:22589535, PubMed:37558654).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P11182 | CA5B Q9Y2D0 | 2 | EBI-359002, EBI-21848083 | |
BINARY | P11182 | COX4I1 P13073 | 2 | EBI-359002, EBI-1056574 | |
BINARY | P11182 | GRPEL2 Q8TAA5 | 3 | EBI-359002, EBI-13943406 | |
BINARY | P11182 | MMAB Q96EY8 | 3 | EBI-359002, EBI-7825413 | |
BINARY | P11182 | MRRF Q96E11 | 3 | EBI-359002, EBI-2855755 |
Protein-protein interaction databases
Miscellaneous
Structure
3D structure databases
Miscellaneous
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 64-139 | Lipoyl-binding | ||||
Sequence: VVQFKLSDIGEGIREVTVKEWYVKEGDTVSQFDSICEVQSDKASVTITSRYDGVIKKLYYNLDDIAYVGKPLVDIE | ||||||
Region | 145-160 | Critical for association with PPM1K | ||||
Sequence: DSEEDVVETPAVSHDE | ||||||
Region | 147-168 | Disordered | ||||
Sequence: EEDVVETPAVSHDEHTHQEIKG | ||||||
Domain | 172-209 | Peripheral subunit-binding (PSBD) | ||||
Sequence: LATPAVRRLAMENNIKLSEVVGSGKDGRILKEDILNYL |
Sequence similarities
Belongs to the 2-oxoacid dehydrogenase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length482
- Mass (Da)53,517
- Last updated2024-05-29 v4
- ChecksumA6CE6E8D532E10FA
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7P0T9W1 | A0A7P0T9W1_HUMAN | DBT | 301 | ||
Q5VVL7 | Q5VVL7_HUMAN | DBT | 320 | ||
A0A7P0Z494 | A0A7P0Z494_HUMAN | DBT | 524 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 321 | in Ref. 4; AAA64512 | ||||
Sequence: Q → P | ||||||
Sequence conflict | 354 | in Ref. 4; AAA64512 | ||||
Sequence: L → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X66785 EMBL· GenBank· DDBJ | CAA47285.1 EMBL· GenBank· DDBJ | mRNA | ||
J03208 EMBL· GenBank· DDBJ | AAA35589.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
M27093 EMBL· GenBank· DDBJ | AAA64512.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BT007372 EMBL· GenBank· DDBJ | AAP36036.1 EMBL· GenBank· DDBJ | mRNA | ||
AL445928 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK313191 EMBL· GenBank· DDBJ | BAG36008.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471097 EMBL· GenBank· DDBJ | EAW72963.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC016675 EMBL· GenBank· DDBJ | AAH16675.1 EMBL· GenBank· DDBJ | mRNA | ||
M19301 EMBL· GenBank· DDBJ | AAA59200.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
X68104 EMBL· GenBank· DDBJ | CAA48225.1 EMBL· GenBank· DDBJ | Genomic DNA |