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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P09622: Variant p.Arg495Gly

Dihydrolipoyl dehydrogenase, mitochondrial
Gene: DLD
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Variant information Variant position: help 495 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 Arginine (R) to Glycine (G) at position 495 (R495G, p.Arg495Gly). 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 large size and basic (R) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In DLDD; loss of enzyme activity; reduced interaction with PDHX. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 495 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 509 The length of the canonical sequence.
Location on the sequence: help ASCEDIARVCHAHPTLSEAF R EANLAASFGKSINF 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                         ASCEDIARVCHAHPTLSEAFREANLAASFGKSINF-

                              ASCEDIARVCHAHPTLSEAFREANLAASFGKSINF

Mouse                         ASCEDIARVCHAHPTLSEAFREANLAAAFGKPINF

Rat                           ASCEDVARVCHAHPTLSEAFREANLAASFGKPINF

Pig                           ASCEDIARVCHAHPTLSEAFREANLAASFGKAINF

Bovine                        ASCEDIARVCHAHPTLSEAFREANLAASFGKSINF

Caenorhabditis elegans        ASAEDVARVCHPHPTLSEAFREANLAAYCGKAINN

Slime mold                    ASCEDIARTCHGHPTLSEAVKEAAMDA-YDKPIHM

Baker's yeast                 ASAEDVARVCHAHPTLSEAFKEANMAA-YDKAIHC

Fission yeast                 ASAEDVARVCHAHPTLSEATKEAMMAAWCGKSIHF
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 36 – 509 Dihydrolipoyl dehydrogenase, mitochondrial
Active site 487 – 487 Proton acceptor
Modified residue 502 – 502 Phosphoserine
Modified residue 505 – 505 N6-acetyllysine; alternate
Modified residue 505 – 505 N6-succinyllysine; alternate
Mutagenesis 482 – 482 R -> A. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 482 – 482 R -> M. Does not affect interaction with PDHX.
Mutagenesis 485 – 485 H -> A. Loss of dehydrogenase activity. Increases proteolytic activity.
Mutagenesis 491 – 491 S -> A. Loss of proteolytic activity. Does not affect dehydrogenase activity.
Mutagenesis 492 – 492 E -> Q. Reduces dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX.
Mutagenesis 505 – 505 K -> M. Reduces dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX.
Helix 491 – 503



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; Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex.
Brautigam C.A.; Wynn R.M.; Chuang J.L.; Machius M.; Tomchick D.R.; Chuang D.T.;
Structure 14:611-621(2006)
Cited for: X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) OF 36-509 IN COMPLEX WITH PDHX; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT DLDD GLY-495; Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.
Hong Y.S.; Kerr D.S.; Craigen W.J.; Tan J.; Pan Y.; Lusk M.; Patel M.S.;
Hum. Mol. Genet. 5:1925-1930(1996)
Cited for: VARIANT DLDD GLY-495;
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.