UniProtKB/Swiss-Prot P37840: Variant p.Ala53Thr

Alpha-synuclein
Gene: SNCA
Chromosomal location: 4q21
Variant information

Variant position:  53
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Alanine (A) to Threonine (T) at position 53 (A53T, p.Ala53Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Involvement in disease:  Parkinson disease 1 (PARK1) [MIM:168601]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PARK1; no effect on osmotic stress-induced phosphorylation.
Any additional useful information about the variant.



Sequence information

Variant position:  53
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:   TKEGVLYVGSKTKEGVVHGV  A TVAEKTKEQVTNVGGAVVTG
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                         TKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTG

Gorilla                       TKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTG

Rhesus macaque                TKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTG

Chimpanzee                    TKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTG

Mouse                         TKEGVLYVGSKTKEGVVHGVTTVAEKTKEQVTNVGGAVVTG

Rat                           TKEGVLYVGSKTKEGVVHGVTTVAEKTKEQVTNVGGAVVTG

Bovine                        TKEGVLYVGSKTKEGVVHGVTTVAEKTKEQVTNVGEAVVTG

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 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 39 – 39 Y -> F. No effect on osmotic stress-induced phosphorylation.
Mutagenesis 50 – 50 H -> A. Impairs copper-binding.
Helix 52 – 55


Literature citations

Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation.
Takahashi T.; Yamashita H.; Nagano Y.; Nakamura T.; Ohmori H.; Avraham H.; Avraham S.; Yasuda M.; Matsumoto M.;
J. Biol. Chem. 278:42225-42233(2003)
Cited for: MUTAGENESIS OF TYR-39; TYR-125; TYR-133 AND TYR-136; CHARACTERIZATION OF VARIANT THR-53; PHOSPHORYLATION AT TYR-125;

Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
Polymeropoulos M.H.; Lavedan C.; Leroy E.; Ide S.E.; Dehejia A.; Dutra A.; Pike B.; Root H.; Rubenstein J.; Boyer R.; Stenroos E.S.; Chandrasekharappa S.; Athanassiadou A.; Papapetropoulos T.; Johnson W.G.; Lazzarini A.M.; Duvoisin R.C.; di Iorio G.; Golbe L.I.; Nussbaum R.L.;
Science 276:2045-2047(1997)
Cited for: VARIANT PARK1 THR-53;

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.