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UniProtKB/Swiss-Prot P08559: Variant p.Met282Leu

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene: PDHA1
Chromosomal location: Xp22.1-p22.2
Variant information

Variant position:  282
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Methionine (M) to Leucine (L) at position 282 (M282L, p.Met282Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
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

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  282
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
The length of the canonical sequence.

Location on the sequence:   VREATRFAAAYCRSGKGPIL  M ELQTYRYHGHSMSDPGVSYR
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         VREATRFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVSYR

Chimpanzee                    VREATRFAAAYCRSGKGPILMELQTYRYHGHSMSGPGVSYR

Mouse                         VREATKFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVSYR

Rat                           VREATKFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVSYR

Bovine                        VREATKFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVSYR

Caenorhabditis elegans        VREATKWAKEYCDSGKGPLMMEMATYRYHGHSMSDPGTSYR

Slime mold                    VKEAGKYAAEWCRAGNGPIILEMDTYRYVGHSMSDPGITYR

Baker's yeast                 VYQASKFAKDWCLSGKGPLVLEYETYRYGGHSMSDPGTTYR

Fission yeast                 VLQASKFAKKYTVENSQPLLMEFVTYRYGGHSMSDPGTTYR

Sequence annotation in neighborhood:  
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 31 – 390 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
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.
Beta strand 280 – 285


Literature citations

Submission
Suzuki Y.; Sugano S.; Totoki Y.; Toyoda A.; Takeda T.; Sakaki Y.; Tanaka A.; Yokoyama S.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANT LEU-282;

X chromosome evidence for ancient human histories.
Harris E.E.; Hey J.;
Proc. Natl. Acad. Sci. U.S.A. 96:3320-3324(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 202-336; VARIANT LEU-282;

Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients.
Matthews P.M.; Brown R.M.; Otero L.J.; Marchington D.R.; LeGris M.; Howes R.; Meadows L.S.; Shevell M.; Scriver C.R.; Brown G.K.;
Brain 117:435-443(1994)
Cited for: VARIANTS PDHAD ASN-243; ASN-315 AND HIS-378; VARIANT LEU-282;

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.