Property Summary

NCBI Gene PubMed Count 73
PubMed Score 190.69
PubTator Score 96.80

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (10)

Disease log2 FC p
Multiple myeloma 1.140 5.3e-04
astrocytic glioma -1.200 2.4e-02
osteosarcoma -1.418 2.8e-05
glioblastoma -1.100 9.4e-04
acute quadriplegic myopathy 1.064 1.5e-03
intraductal papillary-mucinous neoplasm ... 1.100 4.1e-03
Pick disease -1.100 3.8e-05
ductal carcinoma in situ -1.100 1.5e-03
invasive ductal carcinoma -1.100 1.1e-02
ovarian cancer 2.100 4.1e-07

Protein-protein Interaction (11)

Gene RIF (28)

PMID Text
26408721 Lack of PDHE1alpha protein expression is associated with Esophageal Squamous Cell Carcinoma.
26309161 oncoprotein HBXIP enhances glucose metabolism reprogramming through suppressing SCO2 and PDHA1 in breast cancer
26107902 MPO and BPI in CD4(+)T-lymphocytes, and PDHA1 and MRPL42 in CD8(+) T-lymphocytes might be used as specific biomarkers of severe asthma progression.
25104357 Phosphorylation at distinct serine and tyrosine residues inhibits PDHA1 through distinct mechanisms to impact active site accessibility.
25060325 High HK2 expression combined with low phosphorylated PDHA1 expression in the invasive front lesions of colorectal tumors is predictive of tumor aggressiveness and survival.
23842279 In the presence of PPARbeta/delta, Vpr induced a 3.3-fold increase in PPAR response element-driven transcriptional activity, a 1.9-fold increase in PDK4 protein expression, and a 1.6-fold increase in the phosphorylated pyruvate dehydrogenase subunit E1alpha.
23842279 HIV-1 Vpr enhances PPARbeta/delta agonist GW501516-induced pyruvate dehydrogenase kinase 4 (PDK4) protein expression and phosphorylation of pyruvate dehydrogenase alpha 1 (PDHE1alpha) at serine 293 in cells
22750801 Expression of the PDHA1 gene was found in all somatic cells, whereas expression of PDHA2 gene was restricted to germ cells. The switch from X-linked to autosomic gene expression occurred in spermatocytes.
22142326 Molecular analysis of PDH1A revealed a novel hemizygous c.1045G>A mutation, predicting a p.A349T missense mutation.
21914562 We provide an efficient stepwise strategy for mutation screening in pyruvate dehydrogenase complex genes and expand the growing list of PDHA1 mutations analyzed at the structural level
21895644 Skin fibroblast culture assay revealed PDH deficiency, confirmed by mutation analysis of the E1 alpha subunit.
21852536 Data show that overexpression of ErbB2 maintains PDH flux by suppressing PDK4 expression in an Erk-dependent manner.
21809123 TNFalpha can inhibit pulmonary artery smooth muscle cells pyruvate dehydrogenase activity and induce a pulmonary arterial hypertension phenotype.
21723463 4 affected female patients with PDHA1 mutations who had with severe cortical atrophy, dilated ventricles, and an incomplete corpus callosum.
21470495 We document the broad variability of clinical symptoms of pdha1 deficiency disease. We proved that normal PDHc activity may not exclude the disease.
20958858 Novel nonsense mutation (R263X) of the E1alpha subunit in pyruvate dehydrogenase complex deficiency
20002461 PDHA1 mutations were screened in 40 patients with biochemically demonstrated pyruvate dehydrogenase complex deficiency deficiency or strong clinical suspicion and changes with probable pathological significance were found in 20.
19586787 AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells.
19517265 In this study the phenotypes of patients with PDH deficiency have been divided into three groups of mutations.
18398624 Our results encourage the use of amino acid supplementation to overcome the metabolic/biochemical changes induced by PDHA1 gene specific mutations associated with mild pyruvate dehydrogenase complex phenotypes.
18023225 two synonymous mutations expand the spectrum of rare PDHA1 splicing mutations, all of which are located in non canonical splice sites.
17957032 Resting PDH protein content and phosphorylation on PDH-E1 alpha sites 1 and 2 were higher in vastus lateralis than in triceps and deltoid as was the activity of oxidative enzymes
17947500 Attenuated PDHa activity contributes to the preferential oxidation of n-6 PUFA during moderate-intensity exercise.
17065338 Short-term elevation in plasma non-esterified fatty acids at rest increases PDH-E1alpha phosphorylation, but exercise overrules this effect and phosphorylation leads to even dephosphorylation during exercise with intralipid infusion.
16967364 Molecular genetic analysis of the X-chromosomal E1alpha subunit of PDH showed three new mutations in phylogenetically conserved areas of the protein: Glu358Lys in patient 1; Arg88Lys in patient 2 and 3 (brothers); and Leu216Ser in patient 4.
16713755 PDHA1 gene mutations may have a role in Pyruvate dehydrogenase E1 subunit deficiency
14708897 determinant spreading might underlie the autoimmunity against Elalpha.
14638692 model of the pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and binding of the E1 and E3 components

AA Sequence

MRKMLAAVSRVLSGASQKPASRVLVASRNFANDATFEIKKCDLHRLEEGPPVTTVLTREDGLKYYRMMQT      1 - 70
VRRMELKADQLYKQKIIRGFCHLCDGQEACCVGLEAGINPTDHLITAYRAHGFTFTRGLSVREILAELTG     71 - 140
RKGGCAKGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKDEVCLTLYGDGAANQGQIFEAYNM    141 - 210
AALWKLPCIFICENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVREATRFAAAYCRSGKGPI    211 - 280
LMELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKDRMVNSNLASVEELKEIDVEVRKEIEDAA    281 - 350
QFATADPEPPLEELGYHIYSSDPPFEVRGANQWIKFKSVS                                  351 - 390
//

Text Mined References (91)

PMID Year Title
26408721 2015 Decreased Expression of PDHE1? Predicts Worse Clinical Outcome in Esophageal Squamous Cell Carcinoma.
26309161 2015 The oncoprotein HBXIP promotes glucose metabolism reprogramming via downregulating SCO2 and PDHA1 in breast cancer.
26107902 [Comparative analysis of the role of CD4(+) and CD8(+) T cells in severe asthma development].
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25104357 2014 Tyr-301 phosphorylation inhibits pyruvate dehydrogenase by blocking substrate binding and promotes the Warburg effect.
25060325 2014 Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1? in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23842279 2013 HIV-1 Vpr enhances PPAR?/?-mediated transcription, increases PDK4 expression, and reduces PDC activity.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23146587 2013 Experimental determination of organelle targeting-peptide cleavage sites using transient expression of green fluorescent protein translational fusions.
23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.
22750801 2012 Pyruvate dehydrogenase complex: mRNA and protein expression patterns of E1? subunit genes in human spermatogenesis.
22142326 2012 Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility.
21914562 2011 Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein.
21895644 2012 Unilateral periventricular leukomalacia in association with pyruvate dehydrogenase deficiency.
21852536 2011 Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation.
21809123 2011 Pyruvate dehydrogenase inhibition by the inflammatory cytokine TNF? contributes to the pathogenesis of pulmonary arterial hypertension.
21723463 2011 MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency.
21630459 2011 Proteomic characterization of the human sperm nucleus.
21470495 2011 Two patients with clinically distinct manifestation of pyruvate dehydrogenase deficiency due to mutations in PDHA1 gene.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
20958858 2010 Novel mutation (R263X) of the E1? subunit in pyruvate dehydrogenase complex deficiency.
20833797 2011 Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20002461 2010 Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19586787 2009 AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells.
19517265 2009 Four novel PDHA1 mutations in pyruvate dehydrogenase deficiency.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19081061 2008 Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18398624 2009 Pyruvate dehydrogenase deficiency: identification of a novel mutation in the PDHA1 gene which responds to amino acid supplementation.
18088087 2008 Phosphoproteome of resting human platelets.
18023225 2008 Two silent substitutions in the PDHA1 gene cause exon 5 skipping by disruption of a putative exonic splicing enhancer.
17957032 2008 Regulation of PDH in human arm and leg muscles at rest and during intense exercise.
17947500 2008 The acute effects of differential dietary fatty acids on human skeletal muscle pyruvate dehydrogenase activity.
17474719 2007 Phosphorylation of serine 264 impedes active site accessibility in the E1 component of the human pyruvate dehydrogenase multienzyme complex.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
17065338 2006 PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion.
16967364 2006 Acute flaccid paralysis as initial symptom in 4 patients with novel E1alpha mutations of the pyruvate dehydrogenase complex.
16713755 2006 Females with PDHA1 gene mutations: a diagnostic challenge.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15772651 2005 The DNA sequence of the human X chromosome.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15302935 2004 Large-scale characterization of HeLa cell nuclear phosphoproteins.
14708897 2003 Epitope mapping on E1alpha subunit of pyruvate dehydrogenase complex with autoantibodies of patients with primary biliary cirrhosis.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14638692 2004 Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components.
12676647 2003 Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.
12651851 2003 Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
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.
10077682 1999 X chromosome evidence for ancient human histories.
9799265 1998 DNA variability and recombination rates at X-linked loci in humans.
9671272 1998 Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity.
9266390 1997 Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.
9029794 1997 Mitochondrial and nuclear genes present conflicting portraits of human origins.
9003499 1997 Refined localization of the pyruvate dehydrogenase E1 alpha gene (PDHA1) by linkage analysis.
8844217 1996 Three new mutations of the pyruvate dehydrogenase alpha subunit: a point mutation (M181V), 3 bp deletion (-R282), and 16 bp insertion/frameshift (K358SVS-->TVDQS).
8664900 1996 Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency.
8504306 1993 Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex.
8498846 1993 Molecular genetic characterization of an X-linked form of Leigh's syndrome.
8199595 1994 Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
8032855 1994 Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients.
7967473 1994 Characterization of a point mutation in the pyruvate dehydrogenase E1 alpha gene from two boys with primary lactic acidaemia.
7887409 1995 Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex.
7853374 1994 Pyruvate dehydrogenase deficiency.
7782287 1995 Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation.
7757088 1995 Pyruvate dehydrogenase complex deficiency due to a point mutation (P188L) within the thiamine pyrophosphate binding loop of the E1 alpha subunit.
7573035 1995 An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein.
7545958 1994 Pyruvate dehydrogenase deficiency caused by a 33 base pair duplication in the PDH E1 alpha subunit.
7273846 1981 The glucose-lactic acid cycle and gluconeogenesis.
3422424 1988 Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase.
3034892 1987 The human pyruvate dehydrogenase complex. Isolation of cDNA clones for the E1 alpha subunit, sequence analysis, and characterization of the mRNA.
2828359 1988 Isolation of a full-length complementary DNA coding for human E1 alpha subunit of the pyruvate dehydrogenase complex.
2748588 1989 Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit.
2745444 1989 Structural organization of the gene for the E1 alpha subunit of the human pyruvate dehydrogenase complex.
2737678 1989 X-chromosome localization of the functional gene for the E1 alpha subunit of the human pyruvate dehydrogenase complex.
2537010 1989 Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.
2227443 1990 Characterization and nucleotide sequence of the gene encoding the human pyruvate dehydrogenase alpha-subunit.
1909401 1991 Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency.
1907799 1991 Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene.
1551669 1992 Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit.
1338114 1992 Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein.
1301207 1992 Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene.
1293379 1992 X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.