BCKDK

Protein identityUniProt · HPA

UniProt accession

O14874

Gene

BCKDK

Ensembl

ENSG00000103507

Chromosome

16

Canonical length

412 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCKD. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

412 residues, UniProt reviewed canonical sequence.

>O14874|BCKDK
     1  MILASVLRSG PGGGLPLRPL LGPALALRAR STSATDTHHV EMARERSKTV TSFYNQSAID
    61  AAAEKPSVRL TPTMMLYAGR SQDGSHLLKS ARYLQQELPV RIAHRIKGFR CLPFIIGCNP
   121  TILHVHELYI RAFQKLTDFP PIKDQADEAQ YCQLVRQLLD DHKDVVTLLA EGLRESRKHI
   181  EDEKLVRYFL DKTLTSRLGI RMLATHHLAL HEDKPDFVGI ICTRLSPKKI IEKWVDFARR
   241  LCEHKYGNAP RVRINGHVAA RFPFIPMPLD YILPELLKNA MRATMESHLD TPYNVPDVVI
   301  TIANNDVDLI IRISDRGGGI AHKDLDRVMD YHFTTAEAST QDPRISPLFG HLDMHSGAQS
   361  GPMHGFGFGL PTSRAYAEYL GGSLQLQSLQ GIGTDVYLRL RHIDGREESF RI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against BCKDK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

81 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about BCKDK.

Disease | AllUniProt

Conditions BCKDK is implicated in, by any mechanism.

• Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) MIM:614923

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 197 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Branched-chain keto acid dehydrogenase kinase deficiency
• Intellectual disability
• See cases
• Maple syrup urine disease type 1A

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.87

gnomAD pLI

0

gnomAD missense Z

1.64

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amino acid catabolic process
• branched-chain amino acid catabolic process
• L-isoleucine catabolic process
• L-leucine catabolic process
• L-valine catabolic process
• lipid biosynthetic process
• regulation of glucose metabolic process
• regulation of pyruvate decarboxylation to acetyl-CoA
• spermatogenesis

Molecular functions

• ATP binding
• kinase activity
• protein serine kinase activity
• protein serine/threonine kinase activity
• protein serine/threonine phosphatase activity
• pyruvate dehydrogenase (acetyl-transferring) kinase activity
• [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity

Cellular components

• mitochondrial matrix
• mitochondrion
• oxoglutarate dehydrogenase complex

Protein domainsUniProt · Pfam · InterPro

• Histidine kinase/HSP90-like ATPase domain
• Histidine kinase domain
• Branched-chain alpha-ketoacid dehydrogenase kinase/Pyruvate dehydrogenase kinase, N-terminal
• Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain superfamily
• Histidine kinase/HSP90-like ATPase superfamily
• PDK/BCKDK protein kinase
• Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
• Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase
• Signal transduction histidine kinase-related protein, C-terminal

KeywordsUniProt

• Acetylation
• ATP-binding
• Autism
• Autism spectrum disorder
• Epilepsy
• Intellectual disability
• Kinase
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of BCKDK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DNAJB1
• STAT3