ATP13A1 manual review notes
Falcon deep research report for ATP13A1
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Falcon research supports ATP13A1 as an ER P5A ATPase whose primary function is ATP-dependent transmembrane-helix dislocation rather than classical ion pumping.
"The best-supported primary function of ATP13A1 is **ATP-dependent dislocation/extraction of transmembrane helices (polypeptide segments)** from the ER membrane."
UniProtKB record for human ATP13A1
Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
Defining the membrane proteome of NK cells.
The identification of novel proteins that interact with the GLP-1 receptor and restrain its activity.
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This GLP-1R interactome study provides interaction-screen context, not a specific ATP13A1 molecular function.
"we sought to identify proteins that interact with the GLP-1R using a membrane-based split ubiquitin yeast two-hybrid (MYTH) assay"
The yeast p5 type ATPase, spf1, regulates manganese transport into the endoplasmic reticulum.
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Human ATP13A1 localizes in a reticular pattern consistent with an ER-resident protein.
"immunohistochemistry of HeLa cells reveals a reticular pattern surrounding the nucleus of the cell as would be expected from an ER resident protein"
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The original manganese-homeostasis study did not prove that Spf1 directly transports manganese.
"can not prove that Spf1 is the direct transporter of Mn2+"
A reference map of the human binary protein interactome.
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HuRI is a proteome-scale binary interaction map, so generic protein-binding rows from it are not informative ATP13A1 functions.
"reference interactome map of human binary protein interactions"
The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase.
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ATP13A1 mediates ATP-dependent extraction of a mitochondrial transmembrane segment from the ER.
"ATP13A1 mediates ATP-dependent removal of a mitochondrial TM from the ER."
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P5A-ATPases remove misinserted terminal hydrophobic helices from the ER as a quality-control function.
"Together, our data support a QC function for P5A-ATPases in removing misinserted terminal hydrophobic helices from the ER."
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The P5A substrate-binding pocket lacks a metal coordination site, arguing against cation transport as the direct activity.
"arguing against the idea that the P5A-ATPase transports cations"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex is a proteome-scale AP-MS interaction network, so generic protein-binding rows from it are not informative ATP13A1 functions.
"BioPlex 3.0, the most complete model of the human interactome to date"
MTCH2 is a mitochondrial outer membrane protein insertase.
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The MTCH2 study independently treats ATP13A1 as an ER dislocase for mislocalized mitochondrial tail-anchored proteins.
"ATP13A1 (19), an ER dislocase for mislocalized mitochondrial TAs"
ATP13A1 transports Mn2+ from cytosol to ER lumen
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Reactome describes an older manganese-transport interpretation that is superseded for ATP13A1 molecular-function review.
"Manganese-transporting ATPase 13A1 (ATP13A1) mediates the transport of manganese (Mn2+) into the endoplasmic reticulum."
Ion transport by P-type ATPases
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Reactome parent pathway describes P-type ATPases primarily as ion pumps, which is too broad for ATP13A1 after the dislocase evidence.
"Most members of this transporter family pump a large variety of cations"
ATP13A1 prevents ERAD of folding-competent mislocalized and misoriented proteins.
An ATP13A1-assisted topogenesis pathway for folding multi-spanning membrane proteins.
ATP13A1 engages SEC61 to facilitate substrate-specific translocation.
Tail-anchored protein C-terminal domains stimulate ATP hydrolysis by the P5A-ATPase Spf1p.
A genome-wide optical pooled screen reveals regulators of cellular antiviral responses.
Mitochondrial antiviral-signalling protein is a client of the BAG6 protein quality control complex.
ATP13A1 Dislocase Hypothesis: Final Report