GTPBP2 — research notes

UniProt: Q9BX10. TRAFAC-class translation-factor GTPase, related to eEF1A/eRF3/Hbs1/GTPBP1.

Core function

GTPBP2 is a translational GTPase that partners PELO in ribosome rescue, particularly important
in neurons. The mouse Gtpbp2 / Pelo axis rescues ribosomes stalled at deficient tRNA; loss (with
the n-Tr20 tRNA mutation in the nmf205 mouse) causes ribosome stalling and neurodegeneration
(Ishimura et al. 2014, Science). In humans, GTPBP2 loss-of-function causes Jaberi-Elahi syndrome
(neurodegeneration with developmental delay, cerebellar atrophy).

• [file:human/GTPBP2/GTPBP2-uniprot.txt "Involved in the rescue of ribosome stalling due to the presence of non-functional tRNA"]
• [file:human/GTPBP2/GTPBP2-uniprot.txt "Interacts with PELO"]
• [file:human/GTPBP2/GTPBP2-uniprot.txt "Has very low GTP-binding activity"]

Distinct from GTPBP1 (PMID:30108131)

Unlike GTPBP1, GTPBP2 lacks eEF1A-like elongation activity and did not stimulate exosomal
degradation; its GTP binding is weak though stimulated by Phe-tRNA.
- PMID:30108131
- The GOA has a NEGATED IDA annotation GO:0003746 translation elongation factor activity (PMID:30108131) — correct: GTPBP2 does NOT have elongation factor activity.

Annotations

• IDA (PMID:30108131): negated translation elongation factor activity (correct negation); GTP binding (weak); alpha-aminoacyl-tRNA binding (Phe-tRNA stimulates GTP binding).
• IPI: PMID:23455924 (PRMT interactome Y2H), PMID:32296183 — protein binding / identical protein binding (GTPBP2 self / GTPBP2 homodimer). Keep non-core.
• Reactome platelet alpha granule / extracellular region (R-HSA-481007) — platelet-proteomics localization, non-core.

Action plan

• Core MF: GO:0005525 GTP binding (weak); the rescue role best as BP GO:0072344 (not currently in GOA — could propose, but stick to existing). Existing has translational elongation IBA — but GTPBP2 lacks elongation activity, so MARK as over-annotated / note negation.
• Negated GO:0003746: ACCEPT (the negation is correct and informative).