tp53bp2a notes

Setup and provenance

• Fetched with just fetch-gene on F1R419 (TrEMBL, "apoptosis-stimulating of p53 protein 2a
  isoform X1", 1060 aa); 11 GOA rows (6 IBA-derived rows incl. IBA/IEA duplicates, 2 IMP from
  PMID:24362258). ZFIN ZDB-GENE-040516-8, Ensembl ENSDARG00000009136, chromosome 13.
• Deep research unavailable: Edison returned 402 Payment Required and the OpenAI key is
  invalid, so no -deep-research-*.md was generated. Literature searched by hand via Europe PMC
  (queries: "tp53bp2a", "tp53bp2b", "aspp2a", "aspp2b", zebrafish AND "ASPP2",
  title searches for ASPP2/53BP2 and p53, Par-3, polarity).
• Part of DANRE_DUPLICATION batch 4 (random sample, seed 20260928); paralog tp53bp2b. Ensembl
  Compara dates the tp53bp2a/tp53bp2b duplication to Osteoglossocephalai (teleost level); gar
  ENSLOCG00000015726 is a one-to-many orthologue of both copies; medaka one-to-one orthologues are
  ENSORLG00000007284 (tp53bp2a) and ENSORLG00000000954 (tp53bp2b) (Ensembl REST, 2026-09-28).

Zebrafish literature

Only one functional paper studies either copy, and it studies both together (abstract only in cache):

• Knockdown/overexpression: both copies restrain embryonic growth, not developmental timing
  PMID:24362258
• Both inhibit Akt signalling, reversed by active Akt
  PMID:24362258
• Both bind Irs-1; the effect needs the ankyrin repeats and SH3 domain
  PMID:24362258
• Human ASPP2 acts the same way in fish
  PMID:24362258
• ZFIN curates RT-PCR and whole-mount in situ data from this paper for both copies
  (ZDB-PUB-140220-26): both detected in all ten adult tissues tested and throughout development,
  with whole-organism in situ annotations only (no restricted domain recorded)
  (output.txt, section 6).
• No mutant, morphant-only phenotype on apoptosis, or p53 interaction has been reported for
  either zebrafish copy.

Mammalian ASPP2 (ancestral function)

• ASPP family defined as p53 cofactors for apoptosis
  PMID:11684014
• Structure: ankyrin repeats + SH3 bind the p53 DNA-binding core
  PMID:8875926
• Polarity / junctions: binds Par-3, maintains tight/adherens junctions
  PMID:20619750
  PMID:20619750
• PP1/YAP scaffold at tight junctions
  PMID:25360797

Own analysis (tp53bp2a-bioinformatics/)

See RESULTS.md. Summary: the copies are 60.9% identical
overall, each ~60% identical to human TP53BP2, but the four ankyrin repeats are 90-100% identical
to human in both; the SH3 domain and the N-terminal Ras-associating (ubiquitin-like) domain are
present in both. Divergence is concentrated in the disordered middle region. Relative-rate test
against gar not significant. Expression: tp53bp2a dominates from gastrula to larva in the whole-
embryo time course (e.g. 91 vs 4 TPM at 50% epiboly); both are maternally provided, tp53bp2b drops
during gastrulation and organogenesis and rises again in larvae; both have broad adult Bgee calls,
tp53bp2a usually higher. No conserved local synteny was detected between the two copies.

Curation decisions (summary)

• p53 binding (IBA, IEA): accept - ankyrin/SH3 p53-binding module intact.
• IMP rows from PMID:24362258: accept negative regulation of PI3K/AKT; modify chordate embryonic
  development to negative regulation of multicellular organism growth (the paper's actual claim).
• NEW: insulin receptor substrate binding (IPI, PMID:24362258).
• signal transduction (IEA via RA domain) modified to the specific PI3K/AKT term.
• nucleus / perinuclear: kept as non-core (ASPP2 is mainly cytoplasmic/junctional).