UniProtKB/SwissProt variant VAR

Variant information

Variant position:

182

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 Phenylalanine (F) to Leucine (L) at position 182 (F182L, p.Phe182Leu).

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 large size and aromatic (F) to medium size and hydrophobic (L)

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

Variant description:

In KRS; decreased protein stability; loss of autophosphorylation; 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.

Sequence information

Variant position:

182

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:

VLRYYLFQGQRYIWIETQQA F YQVSLLDHGRSCDDVHRSRH

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                         VLRYYLFQGQRYIWIETQQAFYQVSLLDHGRSCDDVHRSRH

Mouse                         VLRYYVLQGQRYVWMETQQAFCQVSLLDHGRTCDDVHCSSS

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	66 – 235	Cytoplasmic

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;

PARK9-linked parkinsonism in eastern Asia: mutation detection in ATP13A2 and clinical phenotype.
Ning Y.P.; Kanai K.; Tomiyama H.; Li Y.; Funayama M.; Yoshino H.; Sato S.; Asahina M.; Kuwabara S.; Takeda A.; Hattori T.; Mizuno Y.; Hattori N.;
Neurology 70:1491-1493(2008)
Cited for: VARIANT KRS LEU-182;

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 VARIANT KRS LEU-182; CHARACTERIZATION OF VARIANT SPG78 ILE-517; CHARACTERIZATION OF VARIANT ARG-533; SUBCELLULAR LOCATION; AUTOPHOSPHORYLATION; MUTAGENESIS OF ASP-513;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NQ11: Variant p.Phe182Leu