# UPF2 (Q9HAU5) research notes

## Summary
UPF2 (regulator of nonsense transcripts 2; RENT2) is a core adaptor of the nonsense-mediated mRNA decay (NMD) pathway. Built around tandem MIF4G domains with a C-terminal UPF1-binding region, UPF2 bridges UPF1 (bound to the release factors eRF1/eRF3 at a terminating ribosome) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex that activates NMD. Binding of UPF2 (together with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, committing premature-termination-codon and certain long-3'UTR transcripts to decay. UPF2 acts mainly at the cytoplasmic/perinuclear face of the nuclear envelope and in the cytoplasm, binds spliced mRNA, and has additional reported associations (e.g. telomere/TERRA, mRNA export) peripheral to its core NMD adaptor role.

## Core functions (from review)
- **GO:0035145 exon-exon junction complex** — NMD adaptor that bridges UPF1 (at the terminating ribosome, with eRF1/eRF3) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex.
- **GO:0035145 exon-exon junction complex** — Activator of UPF1 in NMD: UPF2 (with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, driving decay of target mRNAs.

## Provenance
Research and verbatim supporting quotes are recorded inline in `UPF2-ai-review.yaml` (per-annotation `supported_by` and `references` findings). This notes file summarizes the completed review; see the YAML for evidence citations.