Recombinant ATPase ASNA1 homolog (PY02198)
Description
Introduction
ATPase ASNA1, also known as arsenical pump-driving ATPase or arsenite-stimulated ATPase, is an enzyme encoded by the ASNA1 gene in humans . It is a highly conserved protein involved in various cellular processes, including the delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER), vesicle-mediated transport, and chaperoning unfolded proteins during oxidative stress or ATP depletion .
Aliases and Identifiers
ATPase ASNA1 has several aliases and identifiers :
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ASNA1
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ARSA-I
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ARSA1
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ASNA-I
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GET3
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TRC40
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hASNA-I
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arsA arsenite transporter, ATP-binding, homolog 1 (bacterial)
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OMIM: 601913
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MGI: 1928379
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HomoloGene: 31513
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GeneCards: ASNA1
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OMA: ASNA1 - orthologs
Function and Mechanism
ASNA1 is a homolog of the bacterial arsA gene, which, in E. coli, encodes the catalytic component of a multisubunit oxyanion pump responsible for resistance to arsenicals and antimonials . The human ASNA1 protein plays a crucial role in the post-translational insertion of tail-anchored proteins into cellular membranes .
Role in Disease
Biallelic variants in ASNA1 have been linked to severe pediatric cardiomyopathy and early death, highlighting the importance of the tail-anchored membrane protein insertion pathway in cardiac function and disease . Inactivation of Asna1 in pancreatic progenitor cells leads to pancreatic agenesis due to apoptosis of these cells . This suggests a critical role for Asna1 in the survival and differentiation of pancreatic progenitor cells .
Expression and Regulation
Studies on Eimeria tenella (Et) have shown that the ATPase ASNA1 homolog (EtASNA1) is differentially expressed in drug-resistant strains compared to drug-sensitive strains . EtASNA1 expression levels increase with increasing concentrations of anti-coccidial drugs like diclazuril and maduramicin .
Functional Studies
Functional studies have demonstrated that the ATPase activity of Asna1 is essential for maintaining Golgi integrity, syntaxin 5 localization, and the survival of pancreatic progenitor cells . Re-introduction of an ATPase-deficient mutant of Asna1 failed to restore Golgi integrity and differentiation of pancreatic progenitor cells lacking Asna1 .
Interactions
ASNA1 has been shown to interact with FAM71D .
Implications in Cancer Research
USP1/UAF1 complex, which is involved in DNA damage response, can be inhibited by N-benzyl-2-phenylpyrimidin-4-amine derivatives, suggesting a potential target for anticancer therapies .
Tables
| Compound | IC50 (µM) for USP1/UAF1 Inhibition |
|---|---|
| 1 | Value |
| 2 | Value |
| ... | ... |
| 75 | Value |
Note: Table data is based on the reference, with representative compounds listed. Consult the original source for complete data .
Product Specs
Target Background
This ATPase is essential for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER). It recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. The complex then targets the ER via membrane-bound receptors, where the TA protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding induces a closed dimer conformation, facilitating TA protein recognition. ATP hydrolysis is necessary for membrane insertion. Subsequently, the homodimer transitions to an open conformation, reducing its affinity for the membrane-bound receptor and returning it to the cytosol to initiate another round of targeting.
STRING: 352914.XP_730066.1
