ANKRD16 is a vertebrate ankyrin-repeat protein that functions as a proofreading safeguard against translational errors arising from defective alanyl-tRNA synthetase (AlaRS) editing PMID:29769718. It binds directly to the catalytic domain of AlaRS and, through its lysine side chains, captures serine that has been misactivated by AlaRS, thereby preventing serine from being charged onto tRNA-Ala and subsequently misincorporated into nascent peptides PMID:29769718. Genetically, ANKRD16 acts as a downstream suppressor of the neurodegeneration caused by editing-defective AlaRS: deletion of Ankrd16 in the brains of Aars^sti/sti mice produces widespread protein aggregation and neuron loss PMID:29769718. Beyond this serine-capture role at the AlaRS catalytic site, no further mechanistic detail has been characterized in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2018 | High | ANKRD16 binds directly to the catalytic domain of AlaRS (alanyl-tRNA synthetase), and serine misactivated by AlaRS is captured by the lysine side chains of ANKRD16, thereby preventing charging of serine adenylates to tRNAAla and precluding serine misincorporation in nascent peptides. | PMID:29769718 | Nature |
| 2018 | High | ANKRD16 acts epistatically with the Aars^sti mutation: deletion of Ankrd16 in brains of Aars^sti/sti mice causes widespread protein aggregation and neuron loss, establishing ANKRD16 as a downstream suppressor of neurodegeneration caused by editing-defective AlaRS. | PMID:29769718 | Nature |