UniProtKB/Swiss-Prot P08559: Variant p.Met282Leu

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene: PDHA1
Feedback?

Variant information Variant position:

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

LB/B 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:

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.

Variant rs2229137 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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.
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.