UniProtKB/SwissProt variant VAR

Variant information

Variant position:

30

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 implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Alanine (A) to Proline (P) at position 30 (A30P, p.Ala30Pro).

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 hydrophobic (P)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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, autosomal dominant (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. {ECO:0000269|PubMed:14755719, ECO:0000269|PubMed:23427326, ECO:0000269|PubMed:23457019, ECO:0000269|PubMed:24936070, ECO:0000269|PubMed:25561023, ECO:0000269|PubMed:9197268, ECO:0000269|PubMed:9462735}. 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 oligomerization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104893878 [ dbSNP | Ensembl ]

Sequence information

Variant position:

30

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:

KAKEGVVAAAEKTKQGVAEA A GKTKEGVLYVGSKTKEGVVH

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                         KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Gorilla                       KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Rhesus macaque                KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Chimpanzee                    KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Mouse                         KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Rat                           KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Pig                           KAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVH

Bovine                        KAKEGVVAAAEKTKQGVAEAAGRTKEGVLYVGSKTKEGVVH

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	20 – 30	1
Region	20 – 67	4 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V-X(4)
Metal binding	50 – 50	Copper
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.
Helix	21 – 32

Literature citations

Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
Krueger R.; Kuhn W.; Mueller T.; Woitalla D.; Graeber M.; Koesel S.; Przuntek H.; Epplen J.T.; Schoels L.; Riess O.;
Nat. Genet. 18:106-108(1998)
Cited for: VARIANT PARK1 PRO-30;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P37840: Variant p.Ala30Pro