ATP13A2

Probable cation-transporting ATPase 13A2 is an enzyme that in humans is encoded by the ATP13A2 gene that is involved in the transport of divalent transition metal cations.[5][6][7] It appears to protect cells from manganese[8] and zinc toxicity,[9] possibly by causing cellular efflux and/or lysosomal sequestration; and from iron toxicity, possibly by preserving lysosome integrity against iron-induced lipid peroxidation.[10] However, it potentiates the toxic effects of cadmium and nickel on developing neurites,[11] and of the widely used herbicide paraquat[12] possibly by increasing polyamine uptake.[13]

ATP13A2
Identifiers
Aliases	ATP13A2, CLN12, HSA9947, KRPPD, PARK9, ATPase 13A2, SPG78, ATPase cation transporting 13A2
External IDs	OMIM: 610513 MGI: 1922022 HomoloGene: 56940 GeneCards: ATP13A2
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.13 Start 16,985,958 bp[1] End 17,011,928 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D3 Start 140,986,873 bp[2] End 141,007,330 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • metal ion binding • ATPase activity • GO:0001948 protein binding • hydrolase activity • ATP binding • cupric ion binding • phosphatidic acid binding • zinc ion binding • phosphatidylinositol-3,5-bisphosphate binding • manganese ion binding • calcium-transporting ATPase activity • cation-transporting ATPase activity Cellular component • integral component of membrane • membrane • vesicle membrane • integral component of plasma membrane • transport vesicle • lysosomal lumen • lysosome • vesicle • multivesicular body • neuron projection • integral component of lysosomal membrane • multivesicular body membrane • autophagosome • late endosome • neuronal cell body • lysosomal membrane Biological process • cellular cation homeostasis • cation transport • ion transmembrane transport • regulation of autophagy of mitochondrion • regulation of autophagosome size • regulation of endopeptidase activity • regulation of mitochondrion organization • cellular response to oxidative stress • cellular calcium ion homeostasis • cellular response to manganese ion • cellular iron ion homeostasis • autophosphorylation • cellular zinc ion homeostasis • autophagosome organization • regulation of glucosylceramidase activity • regulation of chaperone-mediated autophagy • negative regulation of neuron death • zinc ion homeostasis • regulation of macroautophagy • regulation of intracellular protein transport • positive regulation of protein secretion • positive regulation of exosomal secretion • peptidyl-aspartic acid autophosphorylation • negative regulation of lysosomal protein catabolic process • cellular response to zinc ion • calcium ion transmembrane transport • regulation of lysosomal protein catabolic process • extracellular exosome biogenesis • polyamine transmembrane transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23400	74772
Ensembl	ENSG00000159363	ENSMUSG00000036622
UniProt	Q9NQ11 Q8N4D4	Q9CTG6
RefSeq (mRNA)	NM_001141973 NM_001141974 NM_022089	NM_001164366 NM_029097 NM_001379619 NM_001379620 NM_001379621 NM_001379622
RefSeq (protein)	NP_001135445 NP_001135446 NP_071372 NP_001135445.1 NP_001135446.1	NP_001157838 NP_083373 NP_001366548 NP_001366549 NP_001366550 NP_001366551
Location (UCSC)	Chr 1: 16.99 – 17.01 Mb	Chr 4: 140.99 – 141.01 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Deficiency is associated with spastic paraplegia and Kufor-Rakeb syndrome, in which there is progressive parkinsonism with dementia.[14]

References

1. GRCh38: Ensembl release 89: ENSG00000159363 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036622 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Schultheis PJ, Hagen TT, O'Toole KK, Tachibana A, Burke CR, McGill DL, Okunade GW, Shull GE (October 2004). "Characterization of the P5 subfamily of P-type transport ATPases in mice". Biochemical and Biophysical Research Communications. 323 (3): 731–8. doi:10.1016/j.bbrc.2004.08.156. PMID 15381061.
6. Ramirez A, Heimbach A, Gründemann J, Stiller B, Hampshire D, Cid LP, Goebel I, Mubaidin AF, Wriekat AL, Roeper J, Al-Din A, Hillmer AM, Karsak M, Liss B, Woods CG, Behrens MI, Kubisch C (October 2006). "Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase". Nature Genetics. 38 (10): 1184–91. doi:10.1038/ng1884. PMID 16964263.
7. "Entrez Gene: ATP13A2 ATPase type 13A2".
8. Tan J, Zhang T, Jiang L, Chi J, Hu D, Pan Q, Wang D, Zhang Z (August 2011). "Regulation of intracellular manganese homeostasis by Kufor-Rakeb syndrome-associated ATP13A2 protein". The Journal of Biological Chemistry. 286 (34): 29654–62. doi:10.1074/jbc.M111.233874. PMC 3191006. PMID 21724849.
9. Tsunemi T, Krainc D (June 2014). "Zn²⁺ dyshomeostasis caused by loss of ATP13A2/PARK9 leads to lysosomal dysfunction and alpha-synuclein accumulation". Human Molecular Genetics. 23 (11): 2791–801. doi:10.1093/hmg/ddt572. PMC 4014186. PMID 24334770.
10. Rinaldi DE, Corradi GR, Cuesta LM, Adamo HP, de Tezanos Pinto F (August 2015). "The Parkinson-associated human P5B-ATPase ATP13A2 protects against the iron-induced cytotoxicity". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1848 (8): 1646–55. doi:10.1016/j.bbamem.2015.04.008. PMID 25912790.
11. Podhajska A, Musso A, Trancikova A, Stafa K, Moser R, Sonnay S, Glauser L, Moore DJ (2012-06-29). "Common pathogenic effects of missense mutations in the P-type ATPase ATP13A2 (PARK9) associated with early-onset parkinsonism". PLOS ONE. 7 (6): e39942. Bibcode:2012PLoSO...739942P. doi:10.1371/journal.pone.0039942. PMC 3386943. PMID 22768177.
12. Pinto F, Corradi GR, Hera DP, Adamo HP (February 2012). "CHO cells expressing the human P₅-ATPase ATP13A2 are more sensitive to the toxic effects of herbicide paraquat". Neurochemistry International. 60 (3): 243–8. doi:10.1016/j.neuint.2012.01.002. PMID 22265822.
13. De La Hera DP, Corradi GR, Adamo HP, De Tezanos Pinto F (February 2013). "Parkinson's disease-associated human P5B-ATPase ATP13A2 increases spermidine uptake". The Biochemical Journal. 450 (1): 47–53. doi:10.1042/BJ20120739. PMID 23205587.
14. Online Mendelian Inheritance in Man (OMIM): ATPase, TYPE 13A2; ATP13A2 - 610513

External links

• Human ATP13A2 genome location and ATP13A2 gene details page in the UCSC Genome Browser.

Further reading

• Hampshire DJ, Roberts E, Crow Y, Bond J, Mubaidin A, Wriekat AL, Al-Din A, Woods CG (October 2001). "Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36". Journal of Medical Genetics. 38 (10): 680–2. doi:10.1136/jmg.38.10.680. PMC 1734748. PMID 11584046.
• Di Fonzo A, Chien HF, Socal M, Giraudo S, Tassorelli C, Iliceto G, Fabbrini G, Marconi R, Fincati E, Abbruzzese G, Marini P, Squitieri F, Horstink MW, Montagna P, Libera AD, Stocchi F, Goldwurm S, Ferreira JJ, Meco G, Martignoni E, Lopiano L, Jardim LB, Oostra BA, Barbosa ER, Bonifati V (May 2007). "ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease". Neurology. 68 (19): 1557–62. doi:10.1212/01.wnl.0000260963.08711.08. PMID 17485642.