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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08559: Variant p.His292Leu

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene: PDHA1
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Variant information Variant position: help 292 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Histidine (H) to Leucine (L) at position 292 (H292L, p.His292Leu). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and polar (H) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In PDHAD. Any additional useful information about the variant.


Sequence information Variant position: help 292 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 390 The length of the canonical sequence.
Location on the sequence: help YCRSGKGPILMELQTYRYHG H SMSDPGVSYRTREEIQEVRS The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         YCRSGKGPILMELQTYRYHGHSMSDPGVSYRTREEIQEVRS

Chimpanzee                    YCRSGKGPILMELQTYRYHGHSMSGPGVSYRTREEIQEVRS

Mouse                         YCRSGKGPILMELQTYRYHGHSMSDPGVSYRTREEIQEVRS

Rat                           YCRSGKGPILMELQTYRYHGHSMSDPGVSYRTREEIQEVRS

Bovine                        YCRSGKGPILMELQTYRYHGHSMSDPGVSYRTREEIQEVRS

Caenorhabditis elegans        YCDSGKGPLMMEMATYRYHGHSMSDPGTSYRTREEIQEVRK

Slime mold                    WCRAGNGPIILEMDTYRYVGHSMSDPGITYRTREEVNHVRQ

Baker's yeast                 WCLSGKGPLVLEYETYRYGGHSMSDPGTTYRTRDEIQHMRS

Fission yeast                 YTVENSQPLLMEFVTYRYGGHSMSDPGTTYRSREEVQKVRA
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 30 – 390 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Binding site 292 – 292
Modified residue 277 – 277 N6-succinyllysine
Modified residue 293 – 293 Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
Modified residue 295 – 295 Phosphoserine
Modified residue 300 – 300 Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
Modified residue 301 – 301 Phosphotyrosine
Mutagenesis 293 – 293 S -> A. Reduces enzyme activity. Abolishes inactivation by phosphorylation; when associated with A-232 and A-300.
Mutagenesis 293 – 293 S -> E. Interferes with substrate binding.
Mutagenesis 300 – 300 S -> A. Abolishes inactivation by phosphorylation; when associated with A-232 and A-293.



Literature citations
Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex.
Chun K.; McKay N.; Petrova-Benedict R.; Robinson B.H.;
Hum. Mol. Genet. 2:449-454(1993)
Cited for: VARIANTS PDHAD MET-167; THR-199; ALA-231; GLY-263 AND LEU-292;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.