PDHA1

Protein identityUniProt · HPA

UniProt accession

P08559

Gene

PDHA1

Ensembl

ENSG00000131828

Chromosome

X

Canonical length

390 aa

Protein class

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

Subcellular location

Mitochondria

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), and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

Canonical amino-acid sequenceUniProt

390 residues, UniProt reviewed canonical sequence.

>P08559|PDHA1
     1  MRKMLAAVSR VLSGASQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED
    61  GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA
   121  HGFTFTRGLS VREILAELTG RKGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA
   181  CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST
   241  DYYKRGDFIP GLRVDGMDIL CVREATRFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS
   301  YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP
   361  LEELGYHIYS SDPPFEVRGA NQWIKFKSVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDHA1 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)

0.27

Highest tissue expression

420 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDHA1.

Disease | AllUniProt

Conditions PDHA1 is implicated in, by any mechanism.

• Pyruvate dehydrogenase E1-alpha deficiency (PDHAD) MIM:312170

Disease | GeneticClinVar

395 pathogenic / likely-pathogenic of 1,001 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyruvate dehydrogenase E1-alpha deficiency
• Inborn genetic diseases
• Pyruvate dehydrogenase complex deficiency
• Thyroid cancer, nonmedullary, 1
• PDHA1-related disorder

Disease | AutoantibodyPubMed

Conditions in which antibodies against PDHA1 are reported. Each links to that disease's full target list.

• Liver Cirrhosis, Biliary 5

ReferencesPubMed · IEDB

Publications for PDHA1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.27

gnomAD pLI

0.99

gnomAD missense Z

2.57

DepMap mean gene effect

0.01

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

• glucose metabolic process
• pyruvate decarboxylation to acetyl-CoA
• tricarboxylic acid cycle

Molecular functions

• metal ion binding
• pyruvate dehydrogenase (acetyl-transferring) activity

Cellular components

• mitochondrial matrix
• mitochondrion
• nucleolus
• nucleus
• pyruvate dehydrogenase complex

Protein domainsUniProt · Pfam · InterPro

• Dehydrogenase, E1 component
• Pyruvate dehydrogenase (acetyl-transferring) E1 component, alpha subunit, subgroup y
• Thiamin diphosphate-binding fold
• Pyruvate Dehydrogenase E1 Alpha Subunit
• Dehydrogenase E1 component

KeywordsUniProt

• Acetylation
• Carbohydrate metabolism
• Glucose metabolism
• Leigh syndrome
• Magnesium
• Metal-binding
• Mitochondrion
• Oxidoreductase
• Phosphoprotein
• Primary mitochondrial disease
• Pyruvate
• Thiamine pyrophosphate
• Transit peptide
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of PDHA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DLAT
• IMMT
• PDHB
• PDK1
• STAT5A