Arsenical pump ATPase, ArsA/GET3 (IPR016300)

Short name: ATPase_ArsA/GET3

Overlapping homologous superfamilies

Family relationships


Active extrusion is a common mechanism for the detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. This is particularly important for arsenic extrusion because of its prevalence in the environment and its potential to cause health and environmental problems. In prokaryotes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems. ArsA from Escherichia coli is the catalytic subunit of the ArsAB extrusion pump, providing resistance to arsenite and antimonite. This pump consists of a soluble ATPase (ArsA) and a membrane channel (ArsB). Maintenance of a low intracellular concentration of oxidation produces resistance to the toxic agents. A third protein, ArsC, expands the substrate specificity to allow for arsenate resistance. ArsC reduces arsenate to arsenite, which is subsequently pumped out of the cell [PMID: 1704144]. ArsA contains two nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony. Binding of metalloids to the pump stimulates the ATPase activity [PMID: 10970874].

Homologues of the bacterial ArsA ATPase are found in eukaryotes, where they have several recognised functions unrelated to arsenic resistance [PMID: 20981284]. Caenorhabditis elegans homologue Asna-1 is required for defence against arsenite and antimonite toxicity [PMID: 17419726], and may be also involved in insulin signaling [PMID: 17289575]. The homologue in yeast, GET3/Arr4, is part of the GET complex and not only is involved in stress tolerance to metals and heat [PMID: 12680698], but also specifically recognises transmenbrane domains of tail-anchored (TA) proteins destined for the secretory pathway [PMID: 18724936]. Archaeal GET3 homologues have also been discovered, suggesting that that archaea may possess a TA protein targeting pathway similar to that in eukaryotes [PMID: 20406421, PMID: 21658170].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0005524 ATP binding
GO:0016887 ATPase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.