PDHX

Protein identityUniProt · HPA

UniProt accession

O00330

Gene

PDHX

Ensembl

ENSG00000110435

Chromosome

11

Canonical length

501 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane,Mitochondria

OverviewNCBI Gene

The pyruvate dehydrogenase (PDH) complex is located in the mitochondrial matrix and catalyzes the conversion of pyruvate to acetyl coenzyme A. The PDH complex thereby links glycolysis to Krebs cycle. The PDH complex contains three catalytic subunits, E1, E2, and E3, two regulatory subunits, E1 kinase and E1 phosphatase, and a non-catalytic subunit, E3 binding protein (E3BP). This gene encodes the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex. This protein tethers E3 dimers to the E2 core of the PDH complex. Defects in this gene are a cause of pyruvate dehydrogenase deficiency which results in neurological dysfunction and lactic acidosis in infancy and early childhood. This protein is also a minor antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC eventually leads to cirrhosis and liver failure. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

501 residues, UniProt reviewed canonical sequence.

>O00330|PDHX
     1  MAASWRLGCD PRLLRYLVGF PGRRSVGLVK GALGWSVSRG ANWRWFHSTQ WLRGDPIKIL
    61  MPSLSPTMEE GNIVKWLKKE GEAVSAGDAL CEIETDKAVV TLDASDDGIL AKIVVEEGSK
   121  NIRLGSLIGL IVEEGEDWKH VEIPKDVGPP PPVSKPSEPR PSPEPQISIP VKKEHIPGTL
   181  RFRLSPAARN ILEKHSLDAS QGTATGPRGI FTKEDALKLV QLKQTGKITE SRPTPAPTAT
   241  PTAPSPLQAT AGPSYPRPVI PPVSTPGQPN AVGTFTEIPA SNIRRVIAKR LTESKSTVPH
   301  AYATADCDLG AVLKVRQDLV KDDIKVSVND FIIKAAAVTL KQMPDVNVSW DGEGPKQLPF
   361  IDISVAVATD KGLLTPIIKD AAAKGIQEIA DSVKALSKKA RDGKLLPEEY QGGSFSISNL
   421  GMFGIDEFTA VINPPQACIL AVGRFRPVLK LTEDEEGNAK LQQRQLITVT MSSDSRVVDD
   481  ELATRFLKSF KANLENPIRL A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDHX 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)

0.42

Highest tissue expression

130 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDHX.

Disease | AllUniProt

Conditions PDHX is implicated in, by any mechanism.

• Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) MIM:245349

Disease | GeneticClinVar

39 pathogenic / likely-pathogenic of 452 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyruvate dehydrogenase E3-binding protein deficiency
• Inborn genetic diseases
• Pyruvate dehydrogenase E1-alpha deficiency
• Mitochondrial disease

ReferencesPubMed · IEDB

Publications for PDHX 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)

0.72

gnomAD pLI

0

gnomAD missense Z

-0.2

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

• pyruvate decarboxylation to acetyl-CoA

Molecular functions

• dihydrolipoyllysine-residue acetyltransferase activity

Cellular components

• mitochondrial matrix
• mitochondrion
• nucleoplasm
• plasma membrane
• pyruvate dehydrogenase complex

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• 2-oxoacid dehydrogenase acyltransferase, catalytic domain
• 2-oxo acid dehydrogenase, lipoyl-binding site
• Peripheral subunit-binding domain
• Single hybrid motif
• Chloramphenicol acetyltransferase-like domain superfamily
• E3-binding domain superfamily
• Dihydrolipoamide acetyltransferase/Pyruvate dehydrogenase protein X component
• 2-oxoacid dehydrogenases acyltransferase (catalytic domain)
• Biotin-requiring enzyme
• e3 binding domain

KeywordsUniProt

• Acetylation
• Lipoyl
• Mitochondrion
• Phosphoprotein
• Transit peptide

InteractionsUniProt · HPA

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

• DLD
• SIRT4
• HSCB
• STAT5A