UniProtKB/SwissProt variant VAR

Variant information

Variant position:

72

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

Type of variant:

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:

From Lysine (K) to Glutamate (E) at position 72 (K72E, p.Lys72Glu).

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:

Change from large size and basic (K) to medium size and acidic (E)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

1

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:

In DLDD; reduced dihydrolipoyl dehydrogenase activity; no effect on interaction with PDHX.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121964987 [ dbSNP | Ensembl ]

Sequence information

Variant position:

72

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

Protein sequence length:

509

The length of the canonical sequence.

Location on the sequence:

GGYVAAIKAAQLGFKTVCIE K NETLGGTCLNVGCIPSKALL

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                         GGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALL

                              GGYVAAIKAAQLGFKTVCVEKNETLGGTCLNVGCIPSKALL

Mouse                         GGYVAAIKSAQLGFKTVCIEKNETLGGTCLNVGCIPSKALL

Rat                           GGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALL

Pig                           GGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALL

Caenorhabditis elegans        GGYVAAIKAAQLGMKTVCVEKNATLGGTCLNVGCIPSKALL

Slime mold                    GGYVAGIKAGQLGMKVTVVEKRGKLGGTCLNVGCIPSKALL

Baker's yeast                 AGYVAAIKAAQLGFNTACVEKRGKLGGTCLNVGCIPSKALL

Fission yeast                 GGYVAAIRGAQLGLKTICVEKRGTLGGTCLNVGCIPSKALL

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	36 – 509	Dihydrolipoyl dehydrogenase, mitochondrial
Nucleotide binding	71 – 80	FAD
Binding site	89 – 89	FAD
Modified residue	66 – 66	N6-acetyllysine; alternate
Modified residue	66 – 66	N6-succinyllysine; alternate
Alternative sequence	1 – 99	Missing. In isoform 2.
Mutagenesis	89 – 89	K -> E. Abolishes dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX.

Literature citations

Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex.
Patel M.S.; Korotchkina L.G.; Sidhu S.;
J. Mol. Catal., B Enzym. 61:2-6(2009)
Cited for: CATALYTIC ACTIVITY; INTERACTION WITH PDHX; MUTAGENESIS OF LYS-89; ARG-482; GLU-492 AND LYS-505; CHARACTERIZATION OF VARIANTS DLDD GLU-72; LYS-375; LEU-488 AND GLY-495;

Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.
Liu T.-C.; Kim H.; Arizmendi C.; Kitano A.; Patel M.S.;
Proc. Natl. Acad. Sci. U.S.A. 90:5186-5190(1993)
Cited for: VARIANTS DLDD GLU-72 AND LEU-488;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P09622: Variant p.Lys72Glu