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UniProtKB/Swiss-Prot Q9NQ11: Variant p.Thr517Ile

Polyamine-transporting ATPase 13A2
Gene: ATP13A2
Variant information

Variant position:  517
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 Threonine (T) to Isoleucine (I) at position 517 (T517I, p.Thr517Ile).
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 medium size and polar (T) to medium size and hydrophobic (I)
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

Variant description:  In SPG78; no effect on protein stability; loss of autophosphorylation; loss of lysosomal location; loss of ATPase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  517
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:   HPLRINLGGKLQLVCFDKTG  T LTEDGLDVMGVVPLKGQAFL
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                         HPLRINLGGKLQLVCFDKTGTLTEDGLDVMGVVPLKGQAFL

Mouse                         HPLRINLGGKLRLVCFDKTGTLTEDGLDVMGVVPLKGQVLL

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 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;

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 VARIANT KRS LEU-182; CHARACTERIZATION OF VARIANT SPG78 ILE-517; CHARACTERIZATION OF VARIANT ARG-533; 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.