EIF2D PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: P41214
- 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: EIF2D (also called Ligatin) is a cytoplasmic non-canonical translation factor and the single-polypeptide counterpart of the MCTS1-DENR heterodimer (MCTS1 and DENR together correspond to the N- and C-terminal halves of Ligatin). Containing SUI1, PUA and SWIB modules, EIF2D delivers initiator (Met) and, uniquely, elongator (non-Met) tRNAs into the P-site of the 40S small ribosomal subunit in a GTP-independent, eIF2-independent manner, specifically when the start codon is already positioned in the P-site (as on certain IRESs, leaderless and A-rich mRNAs). In addition to its role in initiation, EIF2D promotes recycling of post-termination 40S subunits by promoting release of deacylated tRNA and mRNA following ABCE1-mediated dissociation of post-termination ribosomal complexes. It is broadly expressed and conserved across eukaryotes.
- Existing/core annotation action counts: ACCEPT: 11; KEEP_AS_NON_CORE: 3; MARK_AS_OVER_ANNOTATED: 1; REMOVE: 2
PN Consistency Summary
- Consistency: Review/notes are accurate and self-consistent: EIF2D (Ligatin) is the single-polypeptide eIF2D-like factor that does GTP-independent P-site tRNA delivery and post-termination 40S recycling/reinitiation (core MF GO:0003743). This CONTRADICTS the PN "Translation termination" placement and GO:0006415 projection — EIF2D is not a release factor. (Same node mis-classification as DENR, its split-paralog partner.)
- PN story / NEW pressure: Projected GO:0006415 translational termination is
more_specific_than_existing_goa. Verified (OLS): GO:0006415 = polypeptide release at a stop codon — not EIF2D's activity. EIF2D's real roles (GO:0001731 preinitiation-complex formation, GO:0032790 ribosome disassembly/recycling, GO:0003743 initiation-factor activity) are already in GOA and reviewed. The projection over-reaches / is biologically wrong; no defensible NEW termination term.
- Evidence alignment: Dossier carries no reference titles. Review anchors PMID:20566627 (GTP-independent P-site tRNA delivery) and PMID:20713520 (Ligatin recycling), both VERIFIED — about initiation/recycling, none about termination. Divergence by omission in dossier.
- Verdict: Mapping mismatch — PN "translation termination" + GO:0006415 contradicts EIF2D's initiation/recycling biology already in GOA. Recommended edits: [MAP] do not project GO:0006415 to EIF2D; reclassify PN node toward reinitiation/40S recycling (GO:0001731 / GO:0032790 already in GOA).
Full Consistency Review
- UniProt: P41214 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
- PN placement:
Translation|Cytosolic translation|Translation termination|tRNA, mRNA release ; PN-node mapping: group Translation termination → GO:0006415 translational termination (mapped, ok_for_propagation); type tRNA, mRNA release no_mapping.
- Consistency: Review/notes are accurate and self-consistent: EIF2D (Ligatin) is the single-polypeptide eIF2D-like factor that does GTP-independent P-site tRNA delivery and post-termination 40S recycling/reinitiation (core MF GO:0003743). This CONTRADICTS the PN "Translation termination" placement and GO:0006415 projection — EIF2D is not a release factor. (Same node mis-classification as DENR, its split-paralog partner.)
- PN story / NEW pressure: Projected GO:0006415 translational termination is
more_specific_than_existing_goa. Verified (OLS): GO:0006415 = polypeptide release at a stop codon — not EIF2D's activity. EIF2D's real roles (GO:0001731 preinitiation-complex formation, GO:0032790 ribosome disassembly/recycling, GO:0003743 initiation-factor activity) are already in GOA and reviewed. The projection over-reaches / is biologically wrong; no defensible NEW termination term.
- Mapping strategy: Reinforces the DENR finding: the
Translation termination|tRNA, mRNA release node lumps post-termination recycling/reinitiation factors (EIF2D, DENR) with genuine release factors. Recommend re-homing EIF2D under reinitiation/40S-recycling and not propagating GO:0006415.
- Evidence alignment: Dossier carries no reference titles. Review anchors PMID:20566627 (GTP-independent P-site tRNA delivery) and PMID:20713520 (Ligatin recycling), both VERIFIED — about initiation/recycling, none about termination. Divergence by omission in dossier.
- Verdict: Mapping mismatch — PN "translation termination" + GO:0006415 contradicts EIF2D's initiation/recycling biology already in GOA. Recommended edits: [MAP] do not project GO:0006415 to EIF2D; reclassify PN node toward reinitiation/40S recycling (GO:0001731 / GO:0032790 already in GOA).
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07c
- review_yaml: genes/human/EIF2D/EIF2D-ai-review.yaml
- PN workbook rows: 1
PN row 1: Translation | Cytosolic translation | Translation termination | tRNA, mRNA release
- UniProt: P41214
- In branches: TR
- PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Translation termination|tRNA, mRNA release
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.
- [group] Translation|Cytosolic translation|Translation termination
status=mapped scope=ok_for_propagation_to_go GO=[GO:0006415 translational termination]
rationale: This PN group denotes cytosolic translation termination and release factors. Translational termination is the shared process target.
- [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.
Projected GO annotations (1)
- GO:0006415 translational termination | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Translation|Cytosolic translation|Translation termination
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.