Property Summary

NCBI Gene PubMed Count 50
PubMed Score 44.52
PubTator Score 92.11

Knowledge Summary

Patent (6,091)

TINX Plot

  Disease (3)

Disease Target Count Z-score Confidence
Obesity 616 3.414 1.7

Expression

  Differential Expression (38)

Disease log2 FC p
gastric cancer 1.600 4.4e-04
pancreatic cancer -3.300 2.2e-03
osteosarcoma -2.031 3.3e-02
ependymoma -1.400 8.8e-05
glioblastoma -1.600 1.2e-02
group 4 medulloblastoma -2.600 2.2e-05
atypical teratoid/rhabdoid tumor -2.100 1.0e-04
medulloblastoma, large-cell -3.500 3.6e-06
juvenile dermatomyositis 2.067 8.8e-06
autosomal dominant Emery-Dreifuss muscul... 2.384 1.2e-02
acute quadriplegic myopathy 1.961 2.7e-02
Atopic dermatitis -1.500 3.7e-02
primary pancreatic ductal adenocarcinoma -3.053 1.8e-03
tuberculosis and treatment for 6 months 2.000 4.5e-03
non-small cell lung cancer -3.701 1.5e-20
intraductal papillary-mucinous adenoma (... -2.700 2.5e-04
intraductal papillary-mucinous carcinoma... -3.500 9.6e-04
intraductal papillary-mucinous neoplasm ... -4.000 6.6e-04
colon cancer -3.000 3.0e-06
lung cancer -2.100 2.2e-05
active Crohn's disease -1.755 8.5e-03
ulcerative colitis -2.500 1.4e-04
breast carcinoma -2.400 3.0e-04
fibroadenoma -3.000 1.3e-03
Breast cancer -3.200 2.9e-10
cystic fibrosis and chronic rhinosinusit... -2.448 4.2e-02
lung adenocarcinoma -3.500 2.7e-29
pediatric high grade glioma -1.600 2.2e-03
pancreatic carcinoma 1.500 2.3e-02
psoriasis -3.600 1.2e-11
Endometriosis -2.330 3.7e-02
mucosa-associated lymphoid tissue lympho... 3.123 3.3e-02
ductal carcinoma in situ -2.700 1.3e-03
invasive ductal carcinoma -3.700 6.0e-03
ovarian cancer -3.800 6.7e-07
pituitary cancer -2.900 2.1e-06
Down syndrome 1.200 3.3e-03
chronic rhinosinusitis -2.311 2.7e-02

Protein-protein Interaction (7)

Gene RIF (31)

PMID Text
27456910 Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1alpha and PDK4 mRNA response in trained human muscle.
26560812 upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification.
26506419 High PDK4 expression is associated with hepatocellular cancer.
26469385 HIV-1 MA increases PDK4 mRNA expression in HepG2 cells
25794976 Swiss PDB Viewer identifies NFkappaB subunit p100/p49 as a potential interacting partner for PDK4. Relationship between PDK4 and apoptosis is suggested.
25609694 ZBTB2 may increase cell proliferation by reprogramming glucose metabolic pathways to favor glycolysis by upregulating PDK4 expression via repression of RelA/p65 expression
25311062 Fatty acids induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors.
25164809 PDK4 promotes tumorigenesis through activation of the CREB-RHEB-mTORC1 signaling cascade.
24837562 Methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after gastric bypass.
23842279 HIV-1 MA increases PDK4 mRNA expression in HepG2 cells
23050013 Data show that the orphan nuclear receptor estrogen related receptor gamma (ERRgamma) plays a critical role in hypoxia-mediated activation of pyruvate dehydrogenase kinase 4 (PDK4) gene expression.
22019269 PDK4 polymorphisms may not be associated with type 2 diabetes or metabolic syndrome.
21904029 The present structures demonstrate the flexible and dynamic aspects of PDK4 in the open conformation and provide a basis for the development of novel inhibitors targeting the nucleotide-binding pocket of PDK4.
21883960 mRNA of PGC-1alpha and PDK4 increases markedly in both type I and type II skeletal muscle after either continuous or interval exercise
21852536 Data show that overexpression of ErbB2 maintains PDH flux by suppressing PDK4 expression in an Erk-dependent manner.
20877624 Observational study of gene-disease association. (HuGE Navigator)
20715114 PDK4 gene is downregulated in colic adenocarcinoma.
18660489 Observational study of gene-disease association. (HuGE Navigator)
18658136 PDK4 with bound ADP exists in equilibrium between the open and the closed conformations
18519799 PDK4 upregulation in adipocytes participates in the hypolipidemic effect of thiazolidinediones through modulation of glyceroneogenesis
17669420 PDK2, PDK3 and PDK4 are primary PPARbeta/delta target genes in humans underlining the importance of the receptor in the control of metabolism
17652214 Accumulation of im lipids plays a more important role than impaired activation of Akt-mediated pathways in the regulation of muscle PDK4 gene expression in lipid-induced acute insulin-resistant states
16757381 retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression
15955060 in human muscle, hormonal and nutritional conditions may control PDK2 and PDK4 mRNA expression via a common signalling mechanism.
15776585 Observational study of genotype prevalence and gene-disease association. (HuGE Navigator)
15721319 activation of FXR may suppress glycolysis and enhance oxidation of fatty acids via inactivation of the pyruvate dehydrogenase complex by increasing PDK4 expression
15581486 Gene expression regulation is affected by retinoic acid and histone acetyation (review).
15047604 Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity.
14966024 mRNA levels are increased in skeletal muscle during fasting
12582211 results support the concept that a reduced tissue availability of fatty acids consequent to a massive lipid malabsorption influences glucose metabolism acting through the regulation of pyruvate dehydrogenase kinase 4
12145475 The expression of the pyruvate dehydrogenase kinase 4 was downregulated in the failing heart.

AA Sequence

MKAARFVLRSAGSLNGAGLVPREVEHFSRYSPSPLSMKQLLDFGSENACERTSFAFLRQELPVRLANILK      1 - 70
EIDILPTQLVNTSSVQLVKSWYIQSLMDLVEFHEKSPDDQKALSDFVDTLIKVRNRHHNVVPTMAQGIIE     71 - 140
YKDACTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIFSDSQTGNPSHIGSIDPNCDVVAVVQDAFEC    141 - 210
SRMLCDQYYLSSPELKLTQVNGKFPDQPIHIVYVPSHLHHMLFELFKNAMRATVEHQENQPSLTPIEVIV    211 - 280
VLGKEDLTIKISDRGGGVPLRIIDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNL    281 - 350
YSLSGYGTDAIIYLKALSSESIEKLPVFNKSAFKHYQMSSEADDWCIPSREPKNLAKEVAM             351 - 411
//

Text Mined References (52)

PMID Year Title
27456910 2016 Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1? and PDK4 mRNA response in trained human muscle.
26560812 2015 Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation.
26506419 2015 Active glycolytic metabolism in CD133(+) hepatocellular cancer stem cells: regulation by MIR-122.
25794976 2015 Pyruvate dehydrogenase kinase 4 (PDK4) could be involved in a regulatory role in apoptosis and a link between apoptosis and insulin resistance.
25609694 2015 ZBTB2 increases PDK4 expression by transcriptional repression of RelA/p65.
25311062 2015 Increased pyruvate dehydrogenase kinase expression in cultured myotubes from obese and diabetic individuals.
25164809 2014 PDK4 protein promotes tumorigenesis through activation of cAMP-response element-binding protein (CREB)-Ras homolog enriched in brain (RHEB)-mTORC1 signaling cascade.
24837562 Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass.
23050013 2012 Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERR?.
22020285 2011 Image-based genome-wide siRNA screen identifies selective autophagy factors.
22019269 2012 Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome.
21904029 2011 Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.
21883960 2012 The effect of continuous and interval exercise on PGC-1? and PDK4 mRNA in type I and type II fibres of human skeletal muscle.
21852536 2011 Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation.
21816445 2012 Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20715114 2011 Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex.
18660489 2008 Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.
18658136 2008 Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.
18519799 2008 Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue.
17669420 2007 Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta.
17652214 2007 Elevated free fatty acids attenuate the insulin-induced suppression of PDK4 gene expression in human skeletal muscle: potential role of intramuscular long-chain acyl-coenzyme A.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
16757381 Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15955060 2005 Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells.
15776585 2002 [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal].
15721319 2005 Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor.
15618316 2005 Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle.
15581486 2004 Mechanisms responsible for regulation of pyruvate dehydrogenase kinase 4 gene expression.
15516373 2005 Are exercise-induced genes induced by exercise?
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15047604 2004 Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
14966024 2004 Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12853948 2003 The DNA sequence of human chromosome 7.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12676647 2003 Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.
12606505 2003 Effect of short-term fasting and refeeding on transcriptional regulation of metabolic genes in human skeletal muscle.
12582211 2003 Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients.
12573248 2003 Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12145475 2002 Downregulation of metabolic gene expression in failing human heart before and after mechanical unloading.
11978179 2002 Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex.
11701428 2001 Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet.
11486000 2001 Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase.
11485553 2001 Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites.
11001762 2000 Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise.
9787110 1998 Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects.
8798399 1996 Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
7499431 1995 Diversity of the pyruvate dehydrogenase kinase gene family in humans.