Overview
| Uniprot ID | O14874 |
|---|
| Protein Name | Branched-chain alpha-ketoacid dehydrogenase kinase |
|---|
| Gene Name | BCKDK |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 89 |
QDGSHLLKSARYLQQ |
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 (PubMed:24449431, PubMed:29779826, PubMed:37558654). 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-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). 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 (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826)
Protein Sequence
10
MILASVLRSG
20
PGGGLPLRPL
30
LGPALALRAR
40
STSATDTHHV
50
EMARERSKTV
60
TSFYNQSAID
70
AAAEKPSVRL
80
TPTMMLYAGR
90
SQDGSHLLKS
100
ARYLQQELPV
110
RIAHRIKGFR
120
CLPFIIGCNP
130
TILHVHELYI
140
RAFQKLTDFP
150
PIKDQADEAQ
160
YCQLVRQLLD
170
DHKDVVTLLA
180
EGLRESRKHI
190
EDEKLVRYFL
200
DKTLTSRLGI
210
RMLATHHLAL
220
HEDKPDFVGI
230
ICTRLSPKKI
240
IEKWVDFARR
250
LCEHKYGNAP
260
RVRINGHVAA
270
RFPFIPMPLD
280
YILPELLKNA
290
MRATMESHLD
300
TPYNVPDVVI
310
TIANNDVDLI
320
IRISDRGGGI
330
AHKDLDRVMD
340
YHFTTAEAST
350
QDPRISPLFG
360
HLDMHSGAQS
370
GPMHGFGFGL
380
PTSRAYAEYL
390
GGSLQLQSLQ
400
GIGTDVYLRL
410
RHIDGREESF
RI
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005759 |
mitochondrial matrix |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0045252 |
oxoglutarate dehydrogenase complex |
| Molecular Function |
GO:0047323 |
[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0016301 |
kinase activity |
| Molecular Function |
GO:0106310 |
protein serine kinase activity |
| Molecular Function |
GO:0004674 |
protein serine/threonine kinase activity |
| Molecular Function |
GO:0004722 |
protein serine/threonine phosphatase activity |
| Molecular Function |
GO:0004740 |
pyruvate dehydrogenase (acetyl-transferring) kinase activity |
| Biological Process |
GO:0009063 |
amino acid catabolic process |
| Biological Process |
GO:0009083 |
branched-chain amino acid catabolic process |
| Biological Process |
GO:0006550 |
L-isoleucine catabolic process |
| Biological Process |
GO:0006552 |
L-leucine catabolic process |
| Biological Process |
GO:0006574 |
L-valine catabolic process |
| Biological Process |
GO:0008610 |
lipid biosynthetic process |
| Biological Process |
GO:0010906 |
regulation of glucose metabolic process |
| Biological Process |
GO:0010510 |
regulation of pyruvate decarboxylation to acetyl-CoA |
| Biological Process |
GO:0007283 |
spermatogenesis |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.