O55028 · BCKD_MOUSE
- ProteinBranched-chain alpha-ketoacid dehydrogenase kinase
- GeneBckdk
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids412 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (By similarity).
Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-334, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (By similarity).
Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (By similarity).
Recognizes phosphosites having SxxE/D canonical motif (By similarity).
Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-334, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (By similarity).
Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (By similarity).
Recognizes phosphosites having SxxE/D canonical motif (By similarity).
Catalytic activity
- ATP + L-seryl-[3-methyl-2-oxobutanoate dehydrogenase] = ADP + H+ + O-phospho-L-seryl-[3-methyl-2-oxobutanoate dehydrogenase]This reaction proceeds in the forward direction.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 279 | ATP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 279 | Mg2+ (UniProtKB | ChEBI); structural | ||||
Sequence: N | ||||||
Binding site | 315 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 328 | K+ (UniProtKB | ChEBI); structural | ||||
Sequence: V | ||||||
Binding site | 330 | K+ (UniProtKB | ChEBI); structural | ||||
Sequence: D | ||||||
Binding site | 333 | K+ (UniProtKB | ChEBI); structural | ||||
Sequence: F | ||||||
Binding site | 334 | ATP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 335 | ATP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 364 | ATP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 367 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 367 | K+ (UniProtKB | ChEBI); structural | ||||
Sequence: G | ||||||
Binding site | 370 | ATP (UniProtKB | ChEBI) | ||||
Sequence: L |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Cellular Component | oxoglutarate dehydrogenase complex | |
Molecular Function | [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity | |
Molecular Function | ATP binding | |
Molecular Function | metal ion binding | |
Molecular Function | protein kinase activity | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Molecular Function | protein serine/threonine phosphatase activity | |
Molecular Function | pyruvate dehydrogenase (acetyl-transferring) kinase activity | |
Biological Process | branched-chain amino acid catabolic process | |
Biological Process | isoleucine catabolic process | |
Biological Process | L-leucine catabolic process | |
Biological Process | lipid biosynthetic process | |
Biological Process | phosphorylation | |
Biological Process | regulation of glucose metabolic process | |
Biological Process | spermatogenesis | |
Biological Process | valine catabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBranched-chain alpha-ketoacid dehydrogenase kinase
- EC number
- Short namesBCKDH kinase ; BCKDHKIN; BDK
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO55028
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Mutant animals are born at the expected Mendelian ratio, but they exhibit a decreased fertility. They are healthy at birth. At 3 weeks of age, they start showing growth retardation. At 12 weeks, they are 15% smaller than their wild-type littermates. Adults develop neurological abnormalities, such as tremors, epileptic seizures and hindlimb clasping. These neurological deficits can be completely abolished when mice are fed with a diet enriched in branched amino acids.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 27 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for transit peptide, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-30 | Mitochondrion | ||||
Sequence: MILTSVLGSGPRSWSSLWPLLGSSLSLRAR | ||||||
Modified residue | 31 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000023453 | 31-412 | Branched-chain alpha-ketoacid dehydrogenase kinase | |||
Sequence: STSATDTHHVELARERSKTVTSFYNQSAIDVAAEKPSVRLTPTMMLYSGRSQDGSHLLKSGRYLQQELPVRIAHRIKGFRSLPFIIGCNPTILHVHELYIRAFQKLTDFPPIKDQADEAQYCQLVRQLLDDHKDVVTLLAEGLRESRKHIQDEKLVRYFLDKTLTSRLGIRMLATHHLALHEDKPDFVGIICTRLSPKKIIEKWVDFARRLCEHKYGNAPRVRINGHVAARFPFIPMPLDYILPELLKNAMRATMESHLDTPYNVPDVVITIANNDIDLIIRISDRGGGIAHKDLDRVMDYHFTTAEASTQDPRINPLFGHLDMHSGGQSGPMHGFGFGLPTSRAYAEYLGGSLQLQSLQGIGTDVYLRLRHIDGREESFRI | ||||||
Modified residue | 52 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 192 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 233 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 356 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 360 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autophosphorylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous.
Induction
Expression in female liver is influenced by circadian rhythm.
Gene expression databases
Interaction
Subunit
Homodimer. Homotetramer (By similarity).
Dimerizes through interaction of two opposing nucleotide-binding domains. Interacts with E2 component of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. Competes with BCKDK for binding to the E2 component; this interaction is modulated by branched-chain alpha-keto acids. At steady state, BCKDH holoenzyme contains BCKDK and BCKDHA is phosphorylated. In response to high levels of branched-chain alpha-keto acids, the inhibitory BCKDK is replaced by activating PPM1K leading to BCKDHA dephosphorylation and BCAA degradation (By similarity).
Dimerizes through interaction of two opposing nucleotide-binding domains. Interacts with E2 component of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. Competes with BCKDK for binding to the E2 component; this interaction is modulated by branched-chain alpha-keto acids. At steady state, BCKDH holoenzyme contains BCKDK and BCKDHA is phosphorylated. In response to high levels of branched-chain alpha-keto acids, the inhibitory BCKDK is replaced by activating PPM1K leading to BCKDHA dephosphorylation and BCAA degradation (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 159-404 | Histidine kinase | ||||
Sequence: LDDHKDVVTLLAEGLRESRKHIQDEKLVRYFLDKTLTSRLGIRMLATHHLALHEDKPDFVGIICTRLSPKKIIEKWVDFARRLCEHKYGNAPRVRINGHVAARFPFIPMPLDYILPELLKNAMRATMESHLDTPYNVPDVVITIANNDIDLIIRISDRGGGIAHKDLDRVMDYHFTTAEASTQDPRINPLFGHLDMHSGGQSGPMHGFGFGLPTSRAYAEYLGGSLQLQSLQGIGTDVYLRLRHID |
Sequence similarities
Belongs to the PDK/BCKDK protein kinase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length412
- Mass (Da)46,588
- Last updated1998-06-01 v1
- Checksum80B3B173AAC8AAD3
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0U1RQ97 | A0A0U1RQ97_MOUSE | Bckdk | 216 | ||
A0A0U1RPT4 | A0A0U1RPT4_MOUSE | Bckdk | 365 | ||
A0A0U1RQ50 | A0A0U1RQ50_MOUSE | Bckdk | 180 | ||
A0A0U1RNL7 | A0A0U1RNL7_MOUSE | Bckdk | 335 | ||
D3Z7R0 | D3Z7R0_MOUSE | Bckdk | 214 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF043070 EMBL· GenBank· DDBJ | AAB97689.1 EMBL· GenBank· DDBJ | mRNA | ||
BC046595 EMBL· GenBank· DDBJ | AAH46595.1 EMBL· GenBank· DDBJ | mRNA |