UniProtKB/Swiss-Prot Q9BXM7: Variant p.Ala537Thr

Serine/threonine-protein kinase PINK1, mitochondrial
Gene: PINK1
Feedback?

Variant information Variant position:

537 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Alanine (A) to Threonine (T) at position 537 (A537T, p.Ala537Thr). 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
Other resources:

Links to websites of interest for the variant.

Variant rs771032673 [ dbSNP | Ensembl ]

Sequence information Variant position:

537 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

581 The length of the canonical sequence.
Location on the sequence:

LALKNLKLDKMVGWLLQQSA A TLLANRLTEKCCVETKMKML 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                         LALK-----------------------NLKLDKMVGWLLQQSAATLLANR-------LTEKCCVETKMKML

Mouse                         LALK-----------------------NLKLDKMIAWLLQQ

Rat                           LALK-----------------------NLKLDKMIAWLLQQ

Caenorhabditis elegans        KQMMEKCGISQMTTLLAGSSKVLSQKINSRLDKVMNLITAE

Drosophila                    KAGG-----------------------MPNSPEILQWLLSL

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	78 – 581	Serine/threonine-protein kinase PINK1, mitochondrial
Topological domain	111 – 581	Cytoplasmic
Mutagenesis	532 – 532	L -> A. Under depolarizing conditions, it results in severely reduced autophosphorylation on S-228 and loss of kinase activation.
Mutagenesis	536 – 536	A -> E. Under depolarizing conditions, it results in loss of interaction with TOMM20 and fails to support PINK1-TOM-TIM23 complex assembly and mitophagy activation.
Mutagenesis	536 – 536	A -> S. Under depolarizing conditions, it fails to support PINK1-TOM-TIM23 complex assembly and mitophagy activation.
Mutagenesis	539 – 539	L -> A. Under depolarizing conditions, it results in severely reduced autophosphorylation on S-228 and loss of kinase activation.
Mutagenesis	540 – 540	L -> A. Under depolarizing conditions, does not affect autophosphorylation on S-228 and kinase activation.
Mutagenesis	540 – 540	L -> K. Under depolarizing conditions, it results in loss of interaction with TOMM20 and fails to support PINK1-TOM-TIM23 complex assembly and mitophagy activation.
Mutagenesis	543 – 543	R -> D. No effect on interaction with TOMM20 and mitophagy activation under depolarizing conditions.
Mutagenesis	543 – 543	R -> G. Under depolarizing conditions, it fails to support PINK1-TOM-TIM23 complex assembly and mitophagy activation.

Literature citations
PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum.
Marongiu R.; Ferraris A.; Ialongo T.; Michiorri S.; Soleti F.; Ferrari F.; Elia A.E.; Ghezzi D.; Albanese A.; Altavista M.C.; Antonini A.; Barone P.; Brusa L.; Cortelli P.; Martinelli P.; Pellecchia M.T.; Pezzoli G.; Scaglione C.; Stanzione P.; Tinazzi M.; Zecchinelli A.; Zeviani M.; Cassetta E.; Garavaglia B.; Dallapiccola B.; Bentivoglio A.R.; Valente E.M.;
Hum. Mutat. 29:565-565(2008)
Cited for: VARIANTS PHE-67; PRO-68; TRP-98; SER-111; VAL-124; MET-145; ASN-186; ILE-257; VAL-268; GLN-276; LEU-296; ILE-317; LEU-322; THR-339; THR-383; VAL-395; THR-442; LYS-476; ASN-525 AND THR-537;

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.