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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]
PDK3 (Pyruvate Dehydrogenase Kinase 3) is a Protein Coding gene. Diseases associated with PDK3 include Charcot-Marie-Tooth Disease, X-Linked Dominant, 6 and Charcot-Marie-Tooth Disease. Among its related pathways are Pyruvate metabolism and Citric Acid (TCA) cycle and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein kinase activity and pyruvate dehydrogenase (acetyl-transferring) kinase activity. An important paralog of this gene is PDK1.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH0XJ024464 | Promoter/Enhancer | 1.9 | EPDnew Ensembl ENCODE CraniofacialAtlas | 610.4 | +0.7 | 680 | 3.8 | RNF2 CREB1 PRDM10 ZNF629 POLR2A BACH1 LARP7 PRDM1 RBFOX2 PATZ1 | PDK3 SNRPEP9 PCYT1B | |
GH0XJ024477 | Enhancer | 0.9 | FANTOM5 ENCODE | 9.6 | +14.6 | 14557 | 4.9 | RNF2 FOS POLR2A PKNOX1 SIN3A RUNX3 ZNF316 ZSCAN5C ZBTB40 MAFF | PDK3 ZFX SNRPEP9 PCYT1B | |
GH0XJ024493 | Enhancer | 1 | Ensembl ENCODE | 8.4 | +29.7 | 29680 | 3.4 | PRDM10 ZNF629 ZNF692 FOXA1 PRDM1 SP1 SOX6 CEBPA SP2 ZXDB | PDK3 SNRPEP9 PCYT1B | |
GH0XJ024491 | Enhancer | 0.8 | Ensembl ENCODE | 9.4 | +26.8 | 26779 | 0.8 | FOXA1 ATF7 ZFX RFX1 CTBP1 NFE2 ZNF316 ZNF217 GATA3 DPF2 | PDK3 SAT1 SNRPEP9 PCYT1B | |
GH0XJ024424 | Enhancer | 0.9 | Ensembl ENCODE | 7.5 | -38.6 | -38564 | 5.1 | SIX5 FOXA1 ZNF143 IRF2 CEBPA SCRT2 ZBTB25 ZNF217 HCFC1 CREM | PDK3 piR-47410-015 RF00017-8247 SUPT20HL1 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IDA | 15861126 |
GO:0004674 | protein serine/threonine kinase activity | IBA,IDA | 11486000 |
GO:0004740 | pyruvate dehydrogenase (acetyl-transferring) kinase activity | TAS,IDA | 11486000 |
GO:0005515 | protein binding | IPI | 15861126 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005730 | nucleolus | IDA | -- |
GO:0005739 | mitochondrion | TAS,IDA | -- |
GO:0005759 | mitochondrial matrix | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Pyruvate metabolism and Citric Acid (TCA) cycle | ||
2 | Nanog in Mammalian ESC Pluripotency |
eNOS Signaling
.48
|
|
3 | Metabolism |
.40
|
|
4 | Signaling by GPCR | ||
5 | Signaling by Retinoic Acid |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005975 | carbohydrate metabolic process | IEA | -- |
GO:0006006 | glucose metabolic process | IEA | -- |
GO:0010510 | regulation of acetyl-CoA biosynthetic process from pyruvate | IMP,TAS | -- |
GO:0010906 | regulation of glucose metabolic process | IMP | 22865452 |
GO:0016310 | phosphorylation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Dihydrolipoate | Experimental | Pharma | Target | 0 | ||
Radicicol | Experimental | Pharma | Target | ATPase/kinase inhibitor, Hsp90 inhibitor. Antifungal antibiotic | 0 | |
ATP | Investigational | Nutra | Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation | 0 | ||
CPI-613 | Investigational | Pharma | PDH/α-KGDH inhibitor | 0 | ||
AZD7545 | Pharma | PDHK inhibitor,potent and selective | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 | |||
Phosphate |
|
14066-19-4, 14265-44-2 |
|
Compound | Action | Cas Number |
---|---|---|
AZD7545 | PDHK inhibitor,potent and selective | 252017-04-2 |
ExUns: | 1a | · | 1b | ^ | 2 | ^ | 3a | · | 3b | ^ | 4 | ^ | 5a | · | 5b | ^ | 6a | · | 6b | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||||
SP3: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PDK3 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | PDK3 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PDK3 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PDK3 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Pdk3 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Pdk3 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | PDK3 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | PDK3 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PDK3 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | pdk3 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | pdk3b 31 |
|
OneToMany | |
pdk3a 30 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | Pdk 30 31 32 |
|
OneToMany | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP010276 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | pdhk-2 30 31 |
|
OneToMany | |
ZK370.5 32 |
|
|
|||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0F27423g 30 |
|
||
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AER270W 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | PKP1 31 |
|
OneToMany | |
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | PDK 30 |
|
||
Soybean (Glycine max) |
eudicotyledons | Gma.3204 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os07g0637300 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | pkp1 30 |
|
||
Bread mold (Neurospora crassa) |
Ascomycetes | NCU06760 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.3938 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 0X pos | Variation | AA Info | Type |
---|---|---|---|---|---|
648471 | Uncertain Significance: Charcot-Marie-Tooth disease, X-linked dominant, 6 | 24,503,492(+) | C/T | SYNONYMOUS_VARIANT | |
650052 | Uncertain Significance: Charcot-Marie-Tooth disease, X-linked dominant, 6 | 24,505,285(+) | G/A | SYNONYMOUS_VARIANT | |
650892 | Uncertain Significance: Charcot-Marie-Tooth disease, X-linked dominant, 6 | 24,503,480(+) | C/T | SYNONYMOUS_VARIANT | |
657567 | Uncertain Significance: Charcot-Marie-Tooth disease, X-linked dominant, 6 | 24,527,634(+) | A/G | MISSENSE_VARIANT | |
696106 | Benign: not provided | 24,534,000(+) | G/A | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv2239e212 | CNV | loss | 25503493 |
dgv2240e212 | CNV | loss | 25503493 |
nsv1119632 | CNV | deletion | 24896259 |
nsv472183 | CNV | novel sequence insertion | 20440878 |
nsv474045 | CNV | novel sequence insertion | 20440878 |
Disorder | Aliases | PubMed IDs |
---|---|---|
charcot-marie-tooth disease, x-linked dominant, 6 |
|
|
charcot-marie-tooth disease |
|
|
tooth disease |
|
|
x-linked charcot-marie-tooth disease |
|
|