HYPK PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q9NX55
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-07c
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: 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.
- Existing/core annotation action counts: ACCEPT: 5; KEEP_AS_NON_CORE: 19
PN Consistency Summary
- Consistency: Mostly consistent, with one tension. Deep research and review agree HYPK is an intrinsically disordered NatA-associated chaperone that (a) suppresses polyQ-HTT aggregation (GO:0044183 protein folding chaperone, EXP/IDA) and (b) is a non-catalytic NatA subunit that INHIBITS NatA N-terminal acetyltransferase activity (core_function GO:0010699 acetyltransferase inhibitor activity). The PN row-1 projection of GO:0006474 (N-terminal acetylation, the catalytic process) sits awkwardly: HYPK does not itself acetylate and the review explicitly frames HYPK as a NatA inhibitor/modulator. So PN's "performs N-terminal acetylation" projection partially contradicts the review's "inhibits/modulates NatA" reading.
- PN story / NEW pressure: PN row 1 → GO:0006474 N-terminal protein amino acid acetylation (verified real). This is NOT in HYPK's GOA, but HYPK is a regulatory/modulator subunit, not a catalytic acetyltransferase — projecting the catalytic process term over-attributes activity. The review's own GO:0010699 acetyltransferase inhibitor activity (MF) and complex membership (GO:0031415 NatA complex) better capture the role. Row 2 (UPS / NACA-domain reader) is correctly no_mapping. Conclusion: over-reaches — GO:0006474 should not be propagated to HYPK as an enabling/involved_in catalytic term.
- Evidence alignment: PN row 1 lists no titles; row 2 lists signature domain IPR044034 (UBA/NAC domain), no PMIDs. Review anchors on PMID:17947297 (chaperone/anti-apoptosis), PMID:18076027 (intrinsically disordered chaperone), PMID:20154145 (HYPK-NatA complex, cotranslational NAT + anti-HTT-aggregation). No citation conflict.
- Verdict: Mostly consistent; PN's catalytic N-terminal-acetylation projection over-reaches for a NatA-modulator. Recommended edits: treat node GO:0006474 as context-only for HYPK (do not propagate the catalytic process term); keep the review's GO:0010699 inhibitor activity + GO:0031415 NatA complex as the accurate captures [MAP].
Full Consistency Review
- UniProt: Q9NX55 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
- PN placement: TWO rows. Row 1 (TR)
Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|Modulator of NatA and NatE complexes (type N-terminal acetylation=mapped→GO:0006474 N-terminal protein amino acid acetylation [new_to_goa]; subtype/group=no_mapping; class/branch=context_only). Row 2 (UPS) Ubiquitin and UBL binding|other protein modifiers|N-terminal acetylation|UBA (NACA) — all no_mapping; class=context_only→GO:0140036 ubiquitin-modified protein reader activity.
- Consistency: Mostly consistent, with one tension. Deep research and review agree HYPK is an intrinsically disordered NatA-associated chaperone that (a) suppresses polyQ-HTT aggregation (GO:0044183 protein folding chaperone, EXP/IDA) and (b) is a non-catalytic NatA subunit that INHIBITS NatA N-terminal acetyltransferase activity (core_function GO:0010699 acetyltransferase inhibitor activity). The PN row-1 projection of GO:0006474 (N-terminal acetylation, the catalytic process) sits awkwardly: HYPK does not itself acetylate and the review explicitly frames HYPK as a NatA inhibitor/modulator. So PN's "performs N-terminal acetylation" projection partially contradicts the review's "inhibits/modulates NatA" reading.
- PN story / NEW pressure: PN row 1 → GO:0006474 N-terminal protein amino acid acetylation (verified real). This is NOT in HYPK's GOA, but HYPK is a regulatory/modulator subunit, not a catalytic acetyltransferase — projecting the catalytic process term over-attributes activity. The review's own GO:0010699 acetyltransferase inhibitor activity (MF) and complex membership (GO:0031415 NatA complex) better capture the role. Row 2 (UPS / NACA-domain reader) is correctly no_mapping. Conclusion: over-reaches — GO:0006474 should not be propagated to HYPK as an enabling/involved_in catalytic term.
- Mapping strategy: Recommend the type-node GO:0006474 be treated as context_only for HYPK (it is a regulator, not a catalyst). The review correctly does not annotate HYPK with N-terminal acetyltransferase activity. UPS-branch no_mappings are appropriate (NatA/UBA-domain reader context, no single safe GO assertion).
- Evidence alignment: PN row 1 lists no titles; row 2 lists signature domain IPR044034 (UBA/NAC domain), no PMIDs. Review anchors on PMID:17947297 (chaperone/anti-apoptosis), PMID:18076027 (intrinsically disordered chaperone), PMID:20154145 (HYPK-NatA complex, cotranslational NAT + anti-HTT-aggregation). No citation conflict.
- Verdict: Mostly consistent; PN's catalytic N-terminal-acetylation projection over-reaches for a NatA-modulator. Recommended edits: treat node GO:0006474 as context-only for HYPK (do not propagate the catalytic process term); keep the review's GO:0010699 inhibitor activity + GO:0031415 NatA complex as the accurate captures [MAP].
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07c
- review_yaml: genes/human/HYPK/HYPK-ai-review.yaml
- PN workbook rows: 2
PN row 1: Translation | Cytosolic translation | Nascent peptide husbandry | N-terminal acetylation of nascent peptide | Modulator of NatA and NatE complexes
- UniProt: Q9NX55
- In branches: TR, UPS
- PN-node mapping records (path + ancestors):
- [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|Modulator of NatA and NatE complexes
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower taxonomy bucket already covered by a curated parent mapping or by gene-level annotations. No additional direct GO mapping is appropriate from this node.
- [type] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide
status=mapped scope=ok_for_propagation_to_go GO=[GO:0006474 N-terminal protein amino acid acetylation]
rationale: This PN type denotes N-terminal acetyltransferase machinery acting on nascent peptides. The GO N-terminal acetylation process is the direct target.
- [group] Translation|Cytosolic translation|Nascent peptide husbandry
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [class] Translation|Cytosolic translation
status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.
PN row 2: Ubiquitin Proteasome System | Ubiquitin and UBL binding | other protein modifiers | N-terminal acetylation | UBA (NACA)
- UniProt: Q9NX55
- In branches: TR, UPS
- Signature domains: IPR044034
- Auxiliary domains: (none)
- PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|other protein modifiers|N-terminal acetylation|UBA (NACA)
status=no_mapping scope= GO=[]
rationale: Reviewed manually as a UPS source node. No single GO term is appropriate for direct propagation from this PN label without narrower context or gene-level evidence.
- [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|other protein modifiers|N-terminal acetylation
status=no_mapping scope= GO=[]
rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|other protein modifiers
status=no_mapping scope= GO=[]
rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
- [branch] Ubiquitin Proteasome System
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.
Projected GO annotations (1)
- GO:0006474 N-terminal protein amino acid acetylation | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.