UPF3B PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q9BZI7
- 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: UPF3B (Regulator of nonsense transcripts 3B; also called UPF3X, hUpf3b, RENT3B) is a core factor of the nonsense-mediated mRNA decay (NMD) pathway, the surveillance mechanism that degrades mRNAs bearing premature termination codons. UPF3B is a peripheral component of the exon-junction complex (EJC) that is deposited upstream of exon-exon junctions after splicing. It acts as a molecular adaptor that bridges the EJC core to the central NMD machinery, binding the EJC (through its C-terminal region that contacts EIF4A3 and the MAGOH-RBM8A heterodimer) and recruiting UPF2, which in turn links to the RNA helicase/ATPase UPF1 at the terminating ribosome; together UPF2 and UPF3B stimulate the ATPase and helicase activities of UPF1 to activate NMD. UPF3B binds spliced mRNA upstream of exon-exon junctions, shuttles between nucleus and cytoplasm, and can also stimulate translation in vitro. The gene is X-linked, and loss-of-function mutations cause X-linked syndromic and non-syndromic intellectual disability (including Lujan-Fryns syndrome), reflecting an important role of NMD in neurodevelopment.
- Existing/core annotation action counts: ACCEPT: 36; KEEP_AS_NON_CORE: 29; MARK_AS_OVER_ANNOTATED: 1
PN Consistency Summary
- Consistency: Gene-level consistent. Deep-research/notes, review YAML and GOA agree UPF3B is the principal active UPF3 paralog: EJC-associated NMD adaptor that recruits UPF2 and links to UPF1, stimulating NMD. Core: GO:0003729 mRNA binding, GO:0035145 EJC, GO:0170010 NMD complex, GO:0000184 NMD (ACCEPT, multiple), and notably GO:2000624 positive regulation of NMD — the correct opposite directionality to its antagonist paralog UPF3A. No internal contradictions; the UPF3A/UPF3B directionality is handled correctly across the pair.
- PN story / NEW pressure: PN groups UPF3B under "Modulation of termination," projecting GO:0006415 as new_to_goa. UPF3B's biology (positive NMD adaptor) is fully captured by GO:0000184 + GO:2000624 + EJC/complex terms. No NEW term is defensible; the termination link is indirect (acts after termination, via the surveillance complex).
- Evidence alignment: PN row carries no reference titles; review well-evidenced (PMID:18066079 UPF2/UPF3 bridge UPF1 / stimulate helicase; UniProt EJC-link FUNCTION; NMD/complex terms). No competing PN citations.
- Verdict: Consistent gene biology with correct positive directionality (mirror of UPF3A); PN group→GO:0006415 over-reaches — UPF3B's role is NMD adaptor (GO:0000184 / GO:2000624), not translational termination.
Full Consistency Review
- UniProt: Q9BZI7 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
- PN placement:
Translation|Cytosolic translation|Translation termination|Modulation of termination ; PN-node mapping: type no_mapping; group mapped, ok_for_propagation → GO:0006415 translational termination; class/branch context_only, too_broad. Projected: GO:0006415 (goa_status=new_to_goa).
- Consistency: Gene-level consistent. Deep-research/notes, review YAML and GOA agree UPF3B is the principal active UPF3 paralog: EJC-associated NMD adaptor that recruits UPF2 and links to UPF1, stimulating NMD. Core: GO:0003729 mRNA binding, GO:0035145 EJC, GO:0170010 NMD complex, GO:0000184 NMD (ACCEPT, multiple), and notably GO:2000624 positive regulation of NMD — the correct opposite directionality to its antagonist paralog UPF3A. No internal contradictions; the UPF3A/UPF3B directionality is handled correctly across the pair.
- PN story / NEW pressure: PN groups UPF3B under "Modulation of termination," projecting GO:0006415 as new_to_goa. UPF3B's biology (positive NMD adaptor) is fully captured by GO:0000184 + GO:2000624 + EJC/complex terms. No NEW term is defensible; the termination link is indirect (acts after termination, via the surveillance complex).
- Mapping strategy: As with the other UPF genes, GROUP→GO:0006415 (translational termination, = peptide release) over-reaches — UPF3B is an EJC/NMD adaptor, not a release factor — and would be an unsupported new GOA assertion. Type-level
no_mapping should govern; UPF3B is already correctly anchored on GO:0000184 and positively-directed GO:2000624.
- Evidence alignment: PN row carries no reference titles; review well-evidenced (PMID:18066079 UPF2/UPF3 bridge UPF1 / stimulate helicase; UniProt EJC-link FUNCTION; NMD/complex terms). No competing PN citations.
- Verdict: Consistent gene biology with correct positive directionality (mirror of UPF3A); PN group→GO:0006415 over-reaches — UPF3B's role is NMD adaptor (GO:0000184 / GO:2000624), not translational termination.
Recommended edits: [MAP] do NOT project GO:0006415 (translational termination) onto UPF3B — it is an EJC/NMD adaptor acting downstream of termination, already correctly anchored on GO:0000184 and GO:2000624 (positive regulation of NMD). Type-level no_mapping should win.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07c
- review_yaml: genes/human/UPF3B/UPF3B-ai-review.yaml
- PN workbook rows: 1
PN row 1: Translation | Cytosolic translation | Translation termination | Modulation of termination
- UniProt: Q9BZI7
- In branches: TR
- PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Translation termination|Modulation of termination
status=no_mapping scope= GO=[]
rationale: Reviewed as a contextual PN bucket. The label is useful for curator triage, but no direct GO mapping is appropriate because propagation would add a process, activity, or localization not shared cleanly by all members.
- [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=new_to_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.