# HYPK (Q9NX55) research notes

## Summary
HYPK (Huntingtin-interacting protein K) is a small, largely intrinsically disordered protein that functions as a ribosome-associated, NatA-associated chaperone. It is a stable component of the N-terminal acetyltransferase A (NatA)/HYPK complex (with the catalytic NAA10 and auxiliary NAA15 subunits), where it binds principally to NAA15 and acts as a negative regulator that reduces the N-terminal acetyltransferase activity of NatA and modulates its interaction with NAA50 (the NatE catalytic subunit). Independently of catalysis, HYPK has chaperone-like activity: it suppresses aggregation of aggregation-prone clients, notably preventing polyglutamine (polyQ) aggregation of an expanded N-terminal huntingtin (HTT) fragment in neuronal cells, an activity it exerts in association with the NatA complex. Through these chaperone and complex-modulating roles HYPK contributes to protein stabilization and is reported to negatively regulate apoptosis. HYPK is found in both the cytoplasm and the nucleus.

## Core functions (from review)
- **GO:0044183 protein folding chaperone** — Intrinsically disordered, ribosome/NatA-associated chaperone that suppresses aggregation of aggregation-prone clients, notably preventing polyglutamine aggregation of N-terminal huntingtin, acting in association with the NatA complex.
- **GO:0010699 acetyltransferase inhibitor activity** — Non-catalytic regulatory subunit of the NatA/HYPK N-terminal acetyltransferase complex that binds NAA15 and reduces (inhibits) the N-terminal acetyltransferase activity of the NAA10-NAA15 (NatA) complex and modulates its interaction with NAA50.

## Provenance
Research and verbatim supporting quotes are recorded inline in `HYPK-ai-review.yaml` (per-annotation `supported_by` and `references` findings). This notes file summarizes the completed review; see the YAML for evidence citations.