Variant position: 477 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 521 The length of the canonical sequence.
Location on the sequence:
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 LEPHVYEWTAGQQGSVSAEH GVGFRKRDVLGYSKPPGALQL
Mouse LEPYVYAWTAEQRGSVSAEH GLGFKKKDVLGYSKPPVAVTL
Rat LEPYVYAWTAEQRGSVSAEH GLGFKKKNVLGYSKPPVAVKL
Bovine LEPYVYEWTAGQRGSVSAEH GLGFKKKDVLGYSKPPEALQL
Zebrafish IEPYVYEWTSQWKGSISAEH GLGLKKRNYIYYSKPSEAVAL
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
14 – 521 D-2-hydroxyglutarate dehydrogenase, mitochondrial
475 – 475 Zinc
476 – 476 D-2-hydroxyglutarate
476 – 476 D-lactate
476 – 476 D-malate
314 – 521 Missing. In isoform 2.
320 – 521 Missing. In isoform 3.
475 – 475 E -> A. Loss of catalytic activity.
476 – 476 H -> A. Loss of catalytic activity.
Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria.
Kranendijk M.; Struys E.A.; Gibson K.M.; Wickenhagen W.V.; Abdenur J.E.; Buechner J.; Christensen E.; de Kremer R.D.; Errami A.; Gissen P.; Gradowska W.; Hobson E.; Islam L.; Korman S.H.; Kurczynski T.; Maranda B.; Meli C.; Rizzo C.; Sansaricq C.; Trefz F.K.; Webster R.; Jakobs C.; Salomons G.S.;
Hum. Mutat. 31:279-283(2010)
Cited for: VARIANTS D2HGA1 TRP-109; LYS-127; VAL-131; SER-147; THR-153; VAL-153; 169-GLN--ALA-521 DEL; TYR-172; LEU-189; VAL-205; VAL-231; SER-233; TYR-375; MET-399; 400-TYR--ALA-521 DEL; HIS-419; THR-426; ASP-439; ALA-444; VAL-446 AND ARG-477; CHARACTERIZATION OF VARIANTS D2HGA1 TRP-109; VAL-153; TYR-172; 400-TYR--ALA-521 DEL; HIS-419 AND THR-426; FUNCTION; CATALYTIC ACTIVITY;
Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations.
Yang J.; Zhu H.; Zhang T.; Ding J.;
Cell Discov. 7:3-3(2021)
Cited for: X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 51-521 IN COMPLEX WITH D-2-HYDROXYGLUTARATE; D-MALATE; D-LACTATE; L-2-HYDROXYGLUTARATE AND 2-OXOGLUTARATE; FUNCTION; CATALYTIC ACTIVITY; ZINC-BINDING SITES; BIOPHYSICOCHEMICAL PROPERTIES; MUTAGENESIS OF ARG-386; THR-390; LYS-401; HIS-434; HIS-441; ASN-443; GLU-475 AND HIS-476; CHARACTERIZATION OF VARIANTS D2HGA1 TRP-109; LYS-127; VAL-131; SER-147; THR-153; VAL-153; TYR-172; LEU-189; VAL-205; VAL-231; SER-233; TYR-375; MET-399; HIS-419; THR-426; ASP-439; ALA-444; VAL-446 AND ARG-477; CHARACTERIZATION OF VARIANT VAL-436;
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.