ATP13A2

Description

The ATP13A2 (ATPase cation transporting 13A2) is a protein-coding gene located on chromosome 1.

ATP13A2 is an enzyme involved in the transport of divalent transition metal cations. It protects cells from manganese and zinc toxicity, possibly by causing cellular efflux and/or lysosomal sequestration, and from iron toxicity by preserving lysosome integrity against iron-induced lipid peroxidation. However, it potentiates the toxic effects of cadmium and nickel on developing neurites, and of paraquat by increasing polyamine uptake. Deficiency is associated with spastic paraplegia and Kufor-Rakeb syndrome, characterized by progressive parkinsonism with dementia.

ATP13A2 is a lysosomal polyamine exporter with high affinity for spermine, also stimulating cellular uptake of polyamines and protecting against polyamine toxicity. It plays a role in intracellular cation homeostasis and neuronal integrity, contributing to cellular zinc homeostasis and conferring protection against manganese and zinc toxicity as well as mitochondrial stress. ATP13A2 is required for proper lysosomal and mitochondrial maintenance and regulates the autophagy-lysosome pathway by controlling SYT11 expression at both transcriptional and post-translational levels. It facilitates the recruitment of deacetylase HDAC6 to lysosomes for CTTN deacetylation, leading to actin polymerization, autophagosome-lysosome fusion and the completion of autophagy. ATP13A2 promotes secretion of exosomes and secretion of SCNA via exosomes. It also plays a role in lipid homeostasis.

ATP13A2 is also known as CLN12, HSA9947, KRPPD, PARK9, SPG78.

Associated Diseases

• Kufor-Rakeb syndrome
• CLN12 disease
• Spastic paraplegia 78, autosomal recessive
• Autosomal recessive spastic paraplegia type 78