View source for 7fjm


==Cryo EM structure of lysosomal ATPase==
<StructureSection load='7fjm' size='340' side='right'caption='[[7fjm]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7fjm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FJM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7fjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fjm OCA], [https://pdbe.org/7fjm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fjm RCSB], [https://www.ebi.ac.uk/pdbsum/7fjm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fjm ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AT132_HUMAN AT132_HUMAN] Autosomal recessive spastic paraplegia type 78;Kufor-Rakeb syndrome;ATP13A2-related juvenile neuronal ceroid lipofuscinosis. 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.<ref>PMID:22388936</ref>   The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/AT132_HUMAN AT132_HUMAN] 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 Mn(2+) and Zn(2+) 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).<ref>PMID:22186024</ref> <ref>PMID:22296644</ref> <ref>PMID:24603074</ref> <ref>PMID:25392495</ref> <ref>PMID:26134396</ref> <ref>PMID:27278822</ref> <ref>PMID:28137957</ref> <ref>PMID:30538141</ref> <ref>PMID:31132336</ref> <ref>PMID:31996848</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.

Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2.,Chen X, Zhou M, Zhang S, Yin J, Zhang P, Xuan X, Wang P, Liu Z, Zhou B, Yang M Cell Discov. 2021 Nov 2;7(1):106. doi: 10.1038/s41421-021-00334-6. PMID:34728622<ref>PMID:34728622</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7fjm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Zhang SS]]