UniProtKB/Swiss-Prot Q9NQ11: Variant p.Gly533Arg

Polyamine-transporting ATPase 13A2
Gene: ATP13A2
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Variant information Variant position:

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

US 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 Glycine (G) to Arginine (R) at position 533 (G533R, p.Gly533Arg). 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 glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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
Variant description:

In KRS; uncertain significance; decreased ATPase activity; no effect on autophosphorylation; no effect on stability; no effect on location. Any additional useful information about the variant.

Sequence information Variant position:

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

1180 The length of the canonical sequence.
Location on the sequence:

DKTGTLTEDGLDVMGVVPLK G QAFLPLVPEPRRLPVGPLLR 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                         DKTGTLTEDGLDVMGVVPLKGQAFLPLVPEPRRLPVGPLLR

Mouse                         DKTGTLTEDGLDVMGVVPLKGQVLLPLVPEPCHLPLGPLLR

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 – 1180	Polyamine-transporting ATPase 13A2
Topological domain	485 – 930	Cytoplasmic
Active site	513 – 513	4-aspartylphosphate intermediate
Mutagenesis	513 – 513	D -> N. Loss of ATPase function, autophosphorylation and protection against mitochondrial stress.
Beta strand	533 – 535

Literature citations
ATP13A2 deficiency disrupts lysosomal polyamine export.
van Veen S.; Martin S.; Van den Haute C.; Benoy V.; Lyons J.; Vanhoutte R.; Kahler J.P.; Decuypere J.P.; Gelders G.; Lambie E.; Zielich J.; Swinnen J.V.; Annaert W.; Agostinis P.; Ghesquiere B.; Verhelst S.; Baekelandt V.; Eggermont J.; Vangheluwe P.;
Nature 578:419-424(2020)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANTS KRS MET-12; ARG-533; THR-746 AND ARG-877; CHARACTERIZATION OF VARIANT SPG8 ILE-517; MUTAGENESIS OF GLU-348; ALA-472; ASP-513; ASP-967 AND LYS-1067; ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease.
Di Fonzo A.; Chien H.F.; Socal M.; Giraudo S.; Tassorelli C.; Iliceto G.; Fabbrini G.; Marconi R.; Fincati E.; Abbruzzese G.; Marini P.; Squitieri F.; Horstink M.W.; Montagna P.; Libera A.D.; Stocchi F.; Goldwurm S.; Ferreira J.J.; Meco G.; Martignoni E.; Lopiano L.; Jardim L.B.; Oostra B.A.; Barbosa E.R.; Bonifati V.;
Neurology 68:1557-1562(2007)
Cited for: VARIANTS KRS MET-12; ARG-504 AND ARG-533; Common pathogenic effects of missense mutations in the P-type ATPase ATP13A2 (PARK9) associated with early-onset parkinsonism.
Podhajska A.; Musso A.; Trancikova A.; Stafa K.; Moser R.; Sonnay S.; Glauser L.; Moore D.J.;
PLoS ONE 7:E39942-E39942(2012)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS KRS MET-12; LEU-182; ARG-504; ARG-533; THR-746 AND ARG-877; SUBCELLULAR LOCATION; Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78).
Estrada-Cuzcano A.; Martin S.; Chamova T.; Synofzik M.; Timmann D.; Holemans T.; Andreeva A.; Reichbauer J.; De Rycke R.; Chang D.I.; van Veen S.; Samuel J.; Schoels L.; Poeppel T.; Mollerup Soerensen D.; Asselbergh B.; Klein C.; Zuchner S.; Jordanova A.; Vangheluwe P.; Tournev I.; Schuele R.;
Brain 140:287-305(2017)
Cited for: INVOLVEMENT IN SPG78; VARIANT SPG78 ILE-517; CHARACTERIZATION OF VARIANTS KRS LEU-182 AND ARG-533; CHARACTERIZATION OF VARIANT SPG78 ILE-517; SUBCELLULAR LOCATION; AUTOPHOSPHORYLATION; MUTAGENESIS OF ASP-513;

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.