BCKDK
entrez
10295
canonical
uniprot
O14874
canonical
ensembl
ENSG00000103507
resolver
ensp
ENSP00000219794
resolver
ensp
ENSP00000287507
resolver
ensp
ENSP00000378404
resolver
genesymbol
BCKDK
resolver
hgnc
HGNC:16902
resolver
uniprot
A8MY43
resolver
uniprot
Q6FGL4
resolver
uniprot
Q96G95
resolver
uniprot
Q96IN5
resolver
uniprot_entry
BCKD_HUMAN
resolver
uniprot_sec
A8MY43
resolver
uniprot_sec
Q6FGL4
resolver
uniprot_sec
Q96G95
resolver
uniprot_sec
Q96IN5
resolver
activity_regulation
ACTIVITY REGULATION: Allosterically inhibited by certain thiazoles and thiophenes: thiazoles increase interaction with DBT/BCKDH-E2, whereas thiophenes reduce this interaction. Inhibited by 3,6- dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) (PubMed:37558654). The ATP binding is mediated by both potassium and magnesium ions (PubMed:37558654). {ECO:0000269|PubMed:37558654}.
uniprot
proteins
amino_acid_sequence
MILASVLRSGPGGGLPLRPLLGPALALRARSTSATDTHHVEMARERSKTVTSFYNQSAIDAAAEKPSVRLTPTMMLYAGRSQDGSHLLKSARYLQQELPVRIAHRIKGFRCLPFIIGCNPTILHVHELYIRAFQKLTDFPPIKDQADEAQYCQLVRQLLDDHKDVVTLLAEGLRESRKHIEDEKLVRYFLDKTLTSRLGIRMLATHHLALHEDKPDFVGIICTRLSPKKIIEKWVDFARRLCEHKYGNAPRVRINGHVAARFPFIPMPLDYILPELLKNAMRATMESHLDTPYNVPDVVITIANNDVDLIIRISDRGGGIAHKDLDRVMDYHFTTAEASTQDPRISPLFGHLDMHSGAQSGPMHGFGFGLPTSRAYAEYLGGSLQLQSLQGIGTDVYLRLRHIDGREESFRI
uniprot
proteins
disease_involvement
DISEASE: Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) [MIM:614923]: A metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids. {ECO:0000269|PubMed:22956686, ECO:0000269|PubMed:24449431}. Note=The disease is caused by variants affecting the gene represented in this entry. A diet enriched in branched amino acids (BCAAs) allows to normalize plasma BCAA levels. This suggests that it may be possible to treat patients with mutations in BCKDK with BCAA supplementation.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
2.7.11.4
uniprot
proteins
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 (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). {ECO:0000269|PubMed:24449431, ECO:0000269|PubMed:29779826, ECO:0000269|PubMed:37558654}.
uniprot
proteins
mass_dalton
46360
uniprot
proteins
pathway_participation
PATHWAY: Protein modification. {ECO:0000269|PubMed:24449431, ECO:0000269|PubMed:29779826}.
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated. {ECO:0000269|PubMed:24449431}.
uniprot
proteins
protein_family
PDK/BCKDK protein kinase family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22589535
uniprot
proteins
pubmed
22956686
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24449431
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
29779826
uniprot
proteins
pubmed
37558654
uniprot
proteins
sequence_length
412
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:Q00972, ECO:0000305|PubMed:24449431}. Note=Detected in the cytosolic compartment of liver cells. {ECO:0000250|UniProtKB:Q00972}.
uniprot
proteins