ATP13A2

This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene

ATPase type 13A2

ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine (PubMed:31996848).
Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (PubMed:31996848).
Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (PubMed:22186024).
Contributes to cellular zinc homeostasis (PubMed:24603074).
Confers cellular protection against Mn2+ and Zn2+ toxicity and mitochondrial stress (PubMed:26134396).
Required for proper lysosomal and mitochondrial maintenance (PubMed:22296644, PubMed:28137957).
Regulates the autophagy-lysosome pathway through the control of SYT11 expression at both transcriptional and post-translational levels (PubMed:27278822).
Facilitates recruitment of deacetylase HDAC6 to lysosomes to deacetylate CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141).
Promotes secretion of exosomes as well as secretion of SCNA via exosomes (PubMed:25392495, PubMed:24603074).
Plays a role in lipid homeostasis (PubMed:31132336).

Autophagosome-lysosome fusion Source: UniProtKB
Autophagosome organization Source: ParkinsonsUK-UCL
Autophagy Source: UniProtKB
Cellular calcium ion homeostasis Source: ParkinsonsUK-UCL
Cellular cation homeostasis Source: ParkinsonsUK-UCL
Cellular iron ion homeostasis Source: ParkinsonsUK-UCL
Cellular response to manganese ion Source: ParkinsonsUK-UCL
Cellular response to oxidative stress Source: ParkinsonsUK-UCL
Cellular response to zinc ion Source: ParkinsonsUK-UCL
Cellular zinc ion homeostasis Source: ParkinsonsUK-UCL
Extracellular exosome biogenesis Source: ParkinsonsUK-UCL
Ion transmembrane transport Source: Reactome
Lipid homeostasis Source: UniProtKB
Lysosomal transport Source: UniProtKB
Negative regulation of lysosomal protein catabolic process Source: ParkinsonsUK-UCL
Negative regulation of neuron death Source: ParkinsonsUK-UCL
Peptidyl-aspartic acid autophosphorylation Source: ParkinsonsUK-UCL
Polyamine transmembrane transport Source: ParkinsonsUK-UCL
Positive regulation of exosomal secretion Source: ParkinsonsUK-UCL
Positive regulation of gene expression Source: UniProtKB
Positive regulation of protein secretion Source: ParkinsonsUK-UCL
Protein autophosphorylation Source: ParkinsonsUK-UCL
Protein localization to lysosome Source: UniProtKB
Regulation of autophagosome size Source: ParkinsonsUK-UCL
Regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
Regulation of chaperone-mediated autophagy Source: ParkinsonsUK-UCL
Regulation of endopeptidase activity Source: ParkinsonsUK-UCL
Regulation of glucosylceramidase activity Source: Ensembl
Regulation of intracellular protein transport Source: ParkinsonsUK-UCL
Regulation of lysosomal protein catabolic process Source: ParkinsonsUK-UCL
Regulation of macroautophagy Source: ParkinsonsUK-UCL
Regulation of mitochondrion organization Source: ParkinsonsUK-UCL
Regulation of protein localization to nucleus Source: UniProtKB
Regulation of ubiquitin-specific protease activity Source: UniProtKB
Spermine transmembrane transport Source: UniProtKB
Zinc ion homeostasis Source: ParkinsonsUK-UCL

Late endosome membrane; Multivesicular body membrane; Lysosome membrane; Autophagosome membrane

Kufor-Rakeb syndrome (KRS): The disease is caused by variants affecting the gene represented in this entry. KRS has also been referred to as neuronal ceroid lipofuscinosis 12 (CLN12), due to neuronal and glial lipofuscin deposits detected in the cortex, basal nuclei and cerebellum of some patients. A rare form of autosomal recessive juvenile or early-onset, levodopa-responsive parkinsonism. In addition to typical parkinsonian signs, clinical manifestations of Kufor-Rakeb syndrome include behavioral problems, facial tremor, pyramidal tract dysfunction, supranuclear gaze palsy, and dementia.
Spastic paraplegia 78, autosomal recessive (SPG78): A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.

Cytoplasmic: 1-44 aa
Intramembrane: 45-65 aa
Cytoplasmic: 66-235 aa
Helical: 236-253 aa
Lumenal: 254-256 aa
Helical: 257-276 aa
Cytoplasmic: 277-427 aa
Helical: 428-448 aa
Lumenal: 449-463 aa
Helical: 464-484 aa
Cytoplasmic: 485-930 aa
Helical: 931-951 aa
Lumenal: 952-957 aa
Helical: 958-978 aa
Cytoplasmic: 979-994 aa
Helical: 995-1015 aa
Lumenal: 1016-1048 aa
Helical: 1049-1069 aa
Cytoplasmic: 1070-1080 aa
Helical: 1081-1101 aa
Lumenal: 1102-1117 aa
Helical: 1118-1138 aa
Cytoplasmic: 1139-1180 aa

Autophosphorylated (PubMed:26134396, PubMed:28137957). Accumulates in an inactive autophosphorylated state and autophosphorylation is stimulated by phosphatidic acid and phosphatidylinositol 3,5-bisphosphate but not by Mn2+ or Zn2+ (PubMed:26134396). The presence of spermine results in a dose-dependent reduction in autophosphorylation (PubMed:31996848).