Sequence information
Variant position: 50 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 140 The length of the canonical sequence.
Location on the sequence:
AGKTKEGVLYVGSKTKEGVV
H GVATVAEKTKEQVTNVGGAV
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 AGKTKEGVLYVGSKTKEGVVH GVATVAEKTKEQVTNVGGAV
Gorilla AGKTKEGVLYVGSKTKEGVVH GVATVAEKTKEQVTNVGGAV
Rhesus macaque AGKTKEGVLYVGSKTKEGVVH GVATVAEKTKEQVTNVGGAV
Chimpanzee AGKTKEGVLYVGSKTKEGVVH GVATVAEKTKEQVTNVGGAV
Mouse AGKTKEGVLYVGSKTKEGVVH GVTTVAEKTKEQVTNVGGAV
Rat AGKTKEGVLYVGSKTKEGVVH GVTTVAEKTKEQVTNVGGAV
Pig AGKTKEGVLYVGSKTKEGVVH GVTTVAEKTKEQVTNVGEAV
Bovine AGRTKEGVLYVGSKTKEGVVH GVTTVAEKTKEQVTNVGEAV
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
1 – 140
Alpha-synuclein
Repeat
42 – 56
3; approximate
Region
20 – 67
4 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V-X(4)
Metal binding
50 – 50
Copper
Alternative sequence
41 – 54
Missing. In isoform 2-5.
Mutagenesis
35 – 35
E -> K. No effect on oligomerization.
Mutagenesis
39 – 39
Y -> F. No effect on osmotic stress-induced phosphorylation.
Mutagenesis
50 – 50
H -> A. Impairs copper-binding.
Mutagenesis
57 – 57
E -> K. Increases oligomerization.
Literature citations
Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease.
Appel-Cresswell S.; Vilarino-Guell C.; Encarnacion M.; Sherman H.; Yu I.; Shah B.; Weir D.; Thompson C.; Szu-Tu C.; Trinh J.; Aasly J.O.; Rajput A.; Rajput A.H.; Jon Stoessl A.; Farrer M.J.;
Mov. Disord. 28:811-813(2013)
Cited for: VARIANT PARK1 GLN-50;
A novel alpha-synuclein missense mutation in Parkinson disease.
Proukakis C.; Dudzik C.G.; Brier T.; MacKay D.S.; Cooper J.M.; Millhauser G.L.; Houlden H.; Schapira A.H.;
Neurology 80:1062-1064(2013)
Cited for: VARIANT PARK1 GLN-50; CHARACTERIZATION OF VARIANT PARK1 GLN-50;
The H50Q mutation enhances alpha-synuclein aggregation, secretion, and toxicity.
Khalaf O.; Fauvet B.; Oueslati A.; Dikiy I.; Mahul-Mellier A.L.; Ruggeri F.S.; Mbefo M.K.; Vercruysse F.; Dietler G.; Lee S.J.; Eliezer D.; Lashuel H.A.;
J. Biol. Chem. 289:21856-21876(2014)
Cited for: CHARACTERIZATION OF VARIANT PARK1 GLN-50; SUBCELLULAR LOCATION; SUBUNIT; PHOSPHORYLATION AT SER-129;
Molecular determinants of alpha-synuclein mutants' oligomerization and membrane interactions.
Tsigelny I.F.; Sharikov Y.; Kouznetsova V.L.; Greenberg J.P.; Wrasidlo W.; Overk C.; Gonzalez T.; Trejo M.; Spencer B.; Kosberg K.; Masliah E.;
ACS Chem. Neurosci. 6:403-416(2015)
Cited for: CHARACTERIZATION OF VARIANTS PARK1 PRO-30; LYS-46; GLN-50 AND THR-53; MUTAGENESIS OF GLU-35 AND GLU-57; SUBCELLULAR LOCATION; SUBUNIT;
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.