PDK1

Protein identityUniProt · HPA

UniProt accession

Q15118

Gene

PDK1

Ensembl

ENSG00000152256

Chromosome

2

Canonical length

436 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

Canonical amino-acid sequenceUniProt

436 residues, UniProt reviewed canonical sequence.

>Q15118|PDK1
     1  MRLARLLRGA ALAGPGPGLR AAGFSRSFSS DSGSSPASER GVPGQVDFYA RFSPSPLSMK
    61  QFLDFGSVNA CEKTSFMFLR QELPVRLANI MKEISLLPDN LLRTPSVQLV QSWYIQSLQE
   121  LLDFKDKSAE DAKAIYDFTD TVIRIRNRHN DVIPTMAQGV IEYKESFGVD PVTSQNVQYF
   181  LDRFYMSRIS IRMLLNQHSL LFGGKGKGSP SHRKHIGSIN PNCNVLEVIK DGYENARRLC
   241  DLYYINSPEL ELEELNAKSP GQPIQVVYVP SHLYHMVFEL FKNAMRATME HHANRGVYPP
   301  IQVHVTLGNE DLTVKMSDRG GGVPLRKIDR LFNYMYSTAP RPRVETSRAV PLAGFGYGLP
   361  ISRLYAQYFQ GDLKLYSLEG YGTDAVIYIK ALSTDSIERL PVYNKAAWKH YNTNHEADDW
   421  CVPSREPKDM TTFRSA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDK1 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

26 nTPM

Expression across tissuesHPA

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)

0.81

gnomAD pLI

0

gnomAD missense Z

1.15

DepMap mean gene effect

-0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell population proliferation
• glucose metabolic process
• hypoxia-inducible factor-1alpha signaling pathway
• intrinsic apoptotic signaling pathway in response to oxidative stress
• regulation of glucose metabolic process
• regulation of pyruvate decarboxylation to acetyl-CoA

Molecular functions

• ATP binding
• protein kinase activity
• pyruvate dehydrogenase (acetyl-transferring) kinase activity

Cellular components

• mitochondrial matrix
• mitochondrion
• pyruvate 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

KeywordsUniProt

• ATP-binding
• Kinase
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of PDK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PDHA1