Home  |  Contact

UniProtKB/Swiss-Prot Q9NQ11: Variant p.Gly504Arg

Polyamine-transporting ATPase 13A2
Gene: ATP13A2
Variant information

Variant position:  504
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 504 (G504R, p.Gly504Arg).
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; decreased protein stability; increased degradation by proteasome; novel location to endoplasmic reticulum; loss of lysosomal membrane location; impaired autophagosome-lysosome fusion; impaired degradation of protein aggregates.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  504
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:   AQSRLRRQGIFCIHPLRINL  G GKLQLVCFDKTGTLTEDGLD
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                         AQSRLRRQGIFCIHPLRINLGGKLQLVCFDKTGTLTEDGLD

Mouse                         AQSRLRTQGIFCIHPLRINLGGKLRLVCFDKTGTLTEDGLD

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 – 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.


Literature citations

ATP13A2 facilitates HDAC6 recruitment to lysosome to promote autophagosome-lysosome fusion.
Wang R.; Tan J.; Chen T.; Han H.; Tian R.; Tan Y.; Wu Y.; Cui J.; Chen F.; Li J.; Lv L.; Guan X.; Shang S.; Lu J.; Zhang Z.;
J. Cell Biol. 218:267-284(2019)
Cited for: FUNCTION; INTERACTION WITH HDAC6; CHARACTERIZATION OF VARIANTS KRS LEU-182 AND ARG-504;

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: VARIANT KRS ARG-504; VARIANTS MET-12 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;

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.