ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase.
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ANKRD16 binds the AlaRS catalytic domain directly.
"ANKRD16, a vertebrate-specific protein that contains ankyrin repeats, binds directly to the catalytic domain of AlaRS."
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ANKRD16 lysines capture misactivated serine.
"Serine that is misactivated by AlaRS is captured by the lysine side chains of ANKRD16, which prevents the charging of serine adenylates to tRNAAla and precludes serine misincorporation in nascent peptides."
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ANKRD16 acts before tRNA mischarging.
"Thus, ANKRD16 acts prior to formation of mischarged tRNA to enhance translational fidelity."
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ANKRD16 does not deacylate Ser-tRNA(Ala).
"ANKRD16 had no effect on subsequent steps of tRNA mischarging including deacylation of mischarged Ser-tRNAAla"
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K102, K135 and K165 carry the serine adduct.
"highly conserved lysines - K102, K135, and K165 - shifted by 87 Da (the mass of serine)"
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Mutating the three lysines abolishes the effect on pre-transfer editing.
"In contrast to ANKRD16, ANKRD163xArg had no effect on AlaRSA734E pre-transfer editing"
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ANKRD16 stimulates serine-dependent ATP hydrolysis before aminoacylation.
"ANKRD16 binds to AlaRS and prevents misincorporation of serine at alanine codons in nascent peptides by stimulating serine-dependent ATP hydrolysis prior to tRNA aminoacylation via acceptance of misactivated serines."
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ANKRD16 is nuclear and cytoplasmic in brain.
"ANKRD16 was widely expressed in the brain and was detected in the nucleus as well as the cytoplasm"
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Ankrd16 loss is lethal in the AlaRS editing-defective background.
"However, loss of Ankrd16 in Aarssti/sti mice resulted in early embryonic lethality (Extended Data Fig. 7e)."