PDK3

Protein identityUniProt · HPA

UniProt accession

Q15120

Gene

PDK3

Ensembl

ENSG00000067992

Chromosome

X

Canonical length

406 aa

Protein class

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

Subcellular location

Nucleoli,Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

Canonical amino-acid sequenceUniProt

406 residues, UniProt reviewed canonical sequence.

>Q15120|PDK3
     1  MRLFRWLLKQ PVPKQIERYS RFSPSPLSIK QFLDFGRDNA CEKTSYMFLR KELPVRLANT
    61  MREVNLLPDN LLNRPSVGLV QSWYMQSFLE LLEYENKSPE DPQVLDNFLQ VLIKVRNRHN
   121  DVVPTMAQGV IEYKEKFGFD PFISTNIQYF LDRFYTNRIS FRMLINQHTL LFGGDTNPVH
   181  PKHIGSIDPT CNVADVVKDA YETAKMLCEQ YYLVAPELEV EEFNAKAPDK PIQVVYVPSH
   241  LFHMLFELFK NSMRATVELY EDRKEGYPAV KTLVTLGKED LSIKISDLGG GVPLRKIDRL
   301  FNYMYSTAPR PSLEPTRAAP LAGFGYGLPI SRLYARYFQG DLKLYSMEGV GTDAVIYLKA
   361  LSSESFERLP VFNKSAWRHY KTTPEADDWS NPSSEPRDAS KYKAKQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDK3 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)

0.28

Highest tissue expression

34 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDK3.

Disease | AllUniProt

Conditions PDK3 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, X-linked dominant, 6 (CMTX6) MIM:300905

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)

0.55

gnomAD pLI

0.45

gnomAD missense Z

2.32

DepMap mean gene effect

-0.04

DepMap dependency class

selective

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

• cellular response to fatty acid
• cellular response to glucose stimulus
• hypoxia-inducible factor-1alpha signaling pathway
• peptidyl-serine phosphorylation
• peroxisome proliferator activated receptor signaling pathway
• regulation of glucose metabolic process
• regulation of pyruvate decarboxylation to acetyl-CoA
• regulation of reactive oxygen species metabolic process

Molecular functions

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

Cellular components

• mitochondrial matrix
• mitochondrion
• nucleolus

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
• Charcot-Marie-Tooth disease
• Kinase
• Mitochondrion
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of PDK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DLAT