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UniProtKB/Swiss-Prot P09622: Variant p.Pro488Leu

Dihydrolipoyl dehydrogenase, mitochondrial
Gene: DLD
Variant information

Variant position:  488
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 Proline (P) to Leucine (L) at position 488 (P488L, p.Pro488Leu).
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:  -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:  In DLDD; no effect on interaction with PDHX.
Any additional useful information about the variant.

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



Sequence information

Variant position:  488
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:   ALALEYGASCEDIARVCHAH  P TLSEAFREANLAASFGKSIN
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                         ALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSIN

                              ALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSIN

Mouse                         ALALEYGASCEDIARVCHAHPTLSEAFREANLAAAFGKPIN

Rat                           ALALEYGASCEDVARVCHAHPTLSEAFREANLAASFGKPIN

Pig                           ALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKAIN

Caenorhabditis elegans        TLAMEYGASAEDVARVCHPHPTLSEAFREANLAAYCGKAIN

Slime mold                    VLAMEYGASCEDIARTCHGHPTLSEAVKEAAMDAY-DKPIH

Baker's yeast                 GLALEYGASAEDVARVCHAHPTLSEAFKEANMAAY-DKAIH

Fission yeast                 TLALEYGASAEDVARVCHAHPTLSEATKEAMMAAWCGKSIH

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 36 – 509 Dihydrolipoyl dehydrogenase, mitochondrial
Active site 487 – 487 Proton acceptor
Site 473 – 473 Important for interaction with PDHX and activity of multienzyme pyruvate dehydrogenase complex
Modified residue 502 – 502 Phosphoserine
Modified residue 505 – 505 N6-acetyllysine; alternate
Modified residue 505 – 505 N6-succinyllysine; alternate
Mutagenesis 473 – 473 Y -> A. Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 473 – 473 Y -> F. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 473 – 473 Y -> H. Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity.
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.


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;

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.