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The authors conclude that the TRC40 pathway is critical for hearing and propose that otoferlin is an essential substrate of this pathway in hair cells.
Asna1/TRC40 is required at a late step of herpes simplex virus type 1 infection for efficient release of mature virions to the extracellular milieu.
reveal unanticipated complexity in the mutual regulation of the TRC40 receptor subunits and raise the question as to the role of the excess CAML (show CAMLG Proteins) in the endoplasmic reticulum
Emerin (show EMD Proteins) interacts with TRC40 in situ.
The repertoire of VAPB (show VAPB Proteins) interactors is more diverse than previously anticipated and link VAPB (show VAPB Proteins) to the function of ATPase complexes such as p97 (show EIF4G2 Proteins)/FAF1 (show FAF1 Proteins) and ASNA1/transmembrane-domain recognition complex.
Proteins bind to TRC40 and can utilise this component for their delivery to the ER membrane.
PEX19 (show PEX19 Proteins) formed a complex with the peroxisomal tail anchored protein PEX26 (show PEX26 Proteins) in the cytosol and translocated it directly to peroxisomes by a TRC40-independent class I pathway.
Results indicate calcium-modulating cyclophilin ligand (CAML (show CAMLG Proteins)) and WRB (show WRB Proteins) as components of the TRC40 receptor complex and a crucial mechanism for driving ER membrane insertion of TA proteins in mammalian cells.
Post-translational membrane insertion of tail-anchored transmembrane EF-hand Ca2 (show CA2 Proteins)+ sensor calneurons requires the TRC40/Asna1 protein chaperone.
The coiled-coil domain of WRB (show WRB Proteins) is the binding site for TRC40/Asna1.
These findings support a role for the Asna1 ATPase activity in ensuring the survival of pancreatic multipotent progenitor cells , possibly by counteracting p53 (show TP53 Proteins)-mediated apoptosis.
Asna1 ensures retrograde transport and ER and insulin (show INS Proteins) homeostasis in beta-cells. Asna1 KO mice develop hypoinsulinemia, impaired insulin (show INS Proteins) secretion, and glucose intolerance that rapidly progresses to overt diabetes.
These findings indicate that Asna1 plays a crucial role during early embryonic development.
Data show that the parental gene, asna-1, was not targeted by miR (show MYLIP Proteins)-249, presumably because asna-1 is involved in insulin (show INS Proteins) secretion; the cleavage of the asna-1 mRNA might be so detrimental and could be under selective pressure to escape miR (show MYLIP Proteins)-249 targeting.
findings show that worms lacking activity of the asna-1 gene arrest growth reversibly at the L1 stage even when food is abundant; proposed that ASNA1 is an evolutionarily conserved modulator of insulin (show INS Proteins) signaling
As(III)- & Sb(III)-stimulated ArsA ATPase activities are not restricted to bacteria. asna-1 gene from C. elegans encodes functional ArsA ATPase whose activity is stimulated by As(III) & Sb(III), which is critical for As(III) & Sb(III) tolerance.
This gene represents the human homolog of the bacterial arsA gene, encoding the arsenite-stimulated ATPase component of the arsenite transporter responsible for resistance to arsenicals. This protein is also a central component of a transmembrane domain (TMD) recognition complex (TRC) that is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER). It recognizes and selectively binds the TMD of TA proteins in the cytosol, and delivers them to the ER for insertion.
, arsenical pump-driving ATPase
, arsenite-stimulated ATPase
, golgi to ER traffic 3 homolog
, transmembrane domain recognition complex 40 kDa ATPase subunit
, transmembrane domain recognition complex, 40kDa
, arsenical pump-driving atpase
, ATPase Asna1
, arsenite-translocating ATPase
, arsA arsenite transporter, ATP-binding, homolog 1
, ATPase asna1
, arsenical resistance ATPase
, arsenite-transporting ATPase
, arsA arsenite transporter, ATP-binding, homolog 1 (bacterial)
, Arsenical pump-driving ATPase
, Arsenical resistance ATPase
, Arsenite-translocating ATPase
, Arsenite-transporting ATPase
, arsA arsenite transporter, ATP-binding homolog 1
, ATPase ASNA1-like