Tchem PDK1 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial

Protein Summary

Description

Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress. 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]

Uniprot Accession IDs

• Q15118
• B2R6T1
• B7Z937
• D3DPD8
• E9PD65
• Q308M4

Gene Name

• PDK1

Ensembl ID

• ENST00000282077
• ENSP00000282077
• ENSG00000152256
• ENST00000392571
• ENSP00000376352
• ENST00000410055
• ENSP00000386985

Symbol

• PDHK1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.98
PubMedID	0.94
kinase perturbation	0.91
molecular function	0.91
transcription factor binding site profile	0.88

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / [Pyruvate Dehydrogenase (Acetyl-transferring)] Kinase Isozyme 1, Mitochondrial

DTO Classes

Protein / Kinase / Protein Kinase / Atypical Group / Pdhk Family / [Pyruvate Dehydrogenase (Acetyl-transferring)] Kinase Isozyme 1, Mitochondrial

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 138.59   (req: < 5)

Gene RIFs: 36   (req: <= 3)

Antibodies: 636   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 138.59   (req: >= 5)

Gene RIFs: 36   (req: > 3)

Antibodies: 636   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 119

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (119)

Explore Active Ligands

1 – 10 of 119

staurosporine

PDK1Tchem Kinase

pKd : 7.89

CHEMBL4465866

PDK1Tchem Kinase

pKd : 7.96

CHEMBL4576489

PDK1Tchem Kinase

pKd : 8.22

AT-9283

PDK1Tchem Kinase

pKd : 7.92

CHEMBL2347053

PDK1Tchem Kinase

pIC50 : 9.4

VER-246608

PDK1Tchem Kinase

pKi : 7.55

CHEMBL4591977

PDK1Tchem Kinase

pIC50 : 8.3

CHEMBL4519504

PDK1Tchem Kinase

pIC50 : 8.3

AZD7545

PDK1Tchem Kinase

pIC50 : 8.19

US9040717, Compound (3)

PDK1Tchem Kinase

pIC50 : 8.46

Protein-Protein Interactions (125)

Explore Interacting Targets

1 – 10 of 125

• See Interactions on String-DB

PDK3

Tchem

Family:  Kinase

Novelty:  0.05009442

p_int:  1

Score:  0.839

Data Source:  BioPlex,STRINGDB

PDK2

Tchem

Family:  Kinase

Novelty:  0.01502257

p_int:  0.999999962

p_ni:  3.8e-8

Score:  0.91

Data Source:  BioPlex,STRINGDB

FOXD4

Tbio

Family:  TF

Novelty:  0.11166611

p_int:  0.999998293

p_ni:  0.000001707

Score:  0.647

Data Source:  BioPlex,STRINGDB

PDK4

Tchem

Family:  Kinase

Novelty:  0.00410067

p_int:  0.999664796

p_ni:  0.000335204

Score:  0.828

Data Source:  BioPlex,STRINGDB

CRBN

Tclin

Novelty:  0.00385433

p_int:  0.998900553

p_ni:  0.001077012

p_wrong:  0.000022435

Score:  0.234

Data Source:  BioPlex,STRINGDB

NDUFS7

Tclin

Family:  Enzyme

Novelty:  0.01562198

p_int:  0.987629181

p_ni:  0.01236723

p_wrong:  0.00000359

Data Source:  BioPlex

ACAD9

Tbio

Family:  Enzyme

Novelty:  0.03238308

p_int:  0.987560964

p_ni:  0.012438911

p_wrong:  1.25e-7

Score:  0.507

Data Source:  BioPlex,STRINGDB

SLC18A1

Tchem

Family:  Transporter

Novelty:  0.01135292

p_int:  0.982652996

p_ni:  0.017345208

p_wrong:  0.000001796

Data Source:  BioPlex

PDHB

Tbio

Family:  Enzyme

Novelty:  0.01018086

p_int:  0.982590067

p_ni:  0.017409933

Score:  0.988

Data Source:  BioPlex,Reactome,STRINGDB

APLNR

Tchem

Family:  GPCR

Novelty:  0.00224203

p_int:  0.981154959

p_ni:  0.018845041

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (173)

Reactome (8)

KEGG (3)

PathwayCommons (2)

WikiPathways (160)

Metabolism (R-HSA-1430728)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Pyruvate metabolism	31 targets	R-HSA-70268
Reactome	Pyruvate metabolism and Citric Acid (TCA) cycle	55 targets	R-HSA-71406
Reactome	Regulation of pyruvate dehydrogenase (PDH) complex	16 targets	R-HSA-204174
Reactome	Signal Transduction	2704 targets	R-HSA-162582

Name	Explore in Pharos	Explore in Source
Metabolism	2112 targets	R-HSA-1430728
Pyruvate metabolism	31 targets	R-HSA-70268
Pyruvate metabolism and Citric Acid (TCA) cycle	55 targets	R-HSA-71406
Regulation of pyruvate dehydrogenase (PDH) complex	16 targets	R-HSA-204174
Signal Transduction	2704 targets	R-HSA-162582

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (14)

Functions (3)

Components (5)

Processes (6)

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1 – 3 of 3

GO Term	Evidence	Assigned by
protein kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
pyruvate dehydrogenase (acetyl-transferring) kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (2)

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1 – 2 of 2

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
fasting blood glucose measurement	EFO_0004465	1	1	1		46.1
glucose measurement	EFO_0004468	1	1	1		27.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 2 of 2

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
fasting blood glucose measurement	EFO_0004465	1		46.1
glucose measurement	EFO_0004468	1		27.3

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Carbohydrate metabolism
Complete proteome
Glucose metabolism
Kinase
Mitochondrion
Nucleotide-binding
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
fasting blood glucose measurement
glucose measurement

MGI Phenotype Find Similar Targets

No Header	No Header
endocrine/exocrine gland phenotype
reproductive system phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	pyruvate dehydrogenase kinase 1	VGNC:6370	459743
Macaque	pyruvate dehydrogenase kinase 1		697772
Mouse	pyruvate dehydrogenase kinase, isoenzyme 1	MGI:1926119	228026
Rat	pyruvate dehydrogenase kinase 1	RGD:69427	116551
Dog	pyruvate dehydrogenase kinase 1		476828

Species	Name	OMA	EggNOG	Inparanoid
Chimp	pyruvate dehydrogenase kinase 1
Macaque	pyruvate dehydrogenase kinase 1
Mouse	pyruvate dehydrogenase kinase, isoenzyme 1
Rat	pyruvate dehydrogenase kinase 1
Dog	pyruvate dehydrogenase kinase 1

Publication Statistics

PubMed Score 138.59

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PubTator Score 421.82

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Related Publications

Text Mined References (55)

GeneRif Annotations (36)

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PMID	Year	Title