C2ORF76

C2ORF76 (Aim29) is a conserved co-chaperone that functions in the folding cycle of eukaryotic translation elongation factor 1A (eEF1A), acting through the ATP-independent chaperone Zpr1 (PMID:37597513). It recognizes eEF1A specifically in the GTP-bound, pre-hydrolysis conformation, dampens the GTPase activity of the Zpr1·eEF1A complex, and facilitates client exit from the folding cycle, thereby enabling Zpr1 to be recycled (PMID:37597513). Beyond this single characterized role in the Zpr1-dependent folding of eEF1A, no further mechanistic detail has been characterized in the available corpus.

1. 2023 High

   Established that the conserved orphan protein C2ORF76/Aim29 is not a standalone factor but a co-chaperone that couples conformational sensing of eEF1A to the Zpr1 folding cycle, explaining how a dedicated client is released and the chaperone recycled.

   Evidence yeast genetics and microscopy, in vitro biochemical reconstitution, and structural modeling

   PMID:37597513

   Open questions at the time

   • Human C2ORF76 function shown largely through the yeast Aim29 ortholog; cellular role in human cells not directly tested
   • No high-resolution experimental structure of the Aim29·Zpr1·eEF1A complex
   • Physiological consequences of disrupting this co-chaperone in metazoan translation and cell growth unresolved

• Whether C2ORF76 has roles beyond eEF1A folding, and how its activity is regulated or integrated with translation in human cells, remains open.
• No human disease association documented in the corpus
• Regulation, expression control, and tissue context uncharacterized