ced-2 (C. elegans, UniProtKB:Q9NHC3) curation notes

Manual synthesis written during the GO annotation review. Automated deep-research
providers were unavailable for this session, so there is no ced-2-deep-research-*.md
file. All statements below come from cached publications in publications/ and the
UniProt record (ced-2-uniprot.txt).

Identity and domains

• CrkII orthologue: an N-terminal SH2 domain and two SH3 domains, with no catalytic domain
  (UniProt; Pfam SH2, SH3_1, SH3_2; PANTHER PTHR19969:SF5 "CRK-like protein").
• PMID:10707082

Pathway placement

• One of two partially redundant engulfment pathways, ced-2/ced-5/ced-10(/ced-12)
  PMID:10707082.
• Acts in the engulfing cell PMID:10707082.
• Binds CED-5 and forms a ternary complex with CED-5 and CED-12
  PMID:10707082;
  PMID:11703940.
• Crystal structure: the PXXP-binding surface of CED-2 (F125G) is dispensable for rescue; CED-2
  binds the N-terminal region of CED-5 instead
  PMID:21616056
  (abstract-only).
• Upstream inputs:
• PSR-1: endogenous CED-2 co-precipitates with Flag-PSR-1 PMID:25564762; psr-1 acts in the ced-2 pathway for apoptotic germ cells and necrotic cells PMID:25564762.
• MOM-5/Frizzled with GSK-3 and APR-1/APC PMID:20126385. APR-1 binds the CED-2 SH2 domain in a phospho-dependent yeast two-hybrid assay, but not detected in vivo PMID:20126385.
• SRC-1 (UniProt SUBUNIT, PMID:20226672; not cached, not used as evidence here).
• ABL-1 inhibits engulfment partly independently of CED-2 PMID:19402756.

Phenotypes

• Persistent unengulfed corpses; the cells still die
  PMID:6857247
  (the two genes are ced-1 and ced-2).
• Distal tip cell migration defects PMID:10707082;
  PMID:19402756.
• Engulfment genes promote death of weakly signalled cells
  PMID:11449278;
  PMID:11449279.
  Both cached records are abstract-only. Reddien's abstract defines its engulfment genes as an enumerated set
  that includes ced-2, and states PMID:11449278. The GO:1904747 rows rest on that reading.

Curation decisions (summary)

• Bare protein binding (4 partners: CED-5 x3 rows, APR-1, PSR-1): MODIFY to signaling adaptor
  activity (CED-5, PSR-1) or phosphotyrosine residue binding (APR-1, SH2-dependent Y2H).
• GO:1902742 (CED-8 paper, PMID:24225442): ced-2(n1994) is used only in engulfment
  double-mutant assays. MODIFY to GO:1904747, citing Reddien/Hoeppner, with the caveat above.
• GO:1901076 and GO:1903356 (Cabello 2010): unlike CED-1/6/7, the CED-2/5/12 branch is the route
  through which MOM-5 acts for engulfment and DTC migration. CED-2 is core machinery, not a
  regulator, so MODIFY to GO:0043652 and GO:0097628 (distal tip cell migration). Note: no ced-2 allele
  appears in that paper's strain list; ced-2 is mostly referenced as a comparison phenotype.
• Programmed cell death / apoptotic process IMP (persistent-corpse phenotype): MARK_AS_OVER_ANNOTATED.
• Signal transduction IMP: MODIFY to Rac protein signal transduction (GO:0016601).
• IBA RTK binding and enzyme-linked receptor signaling: KEEP_AS_NON_CORE (inherited SH2 adaptor
  capacity; no worm RTK partner shown).
• ced-2 itself (WBGene00000416) appears in the cell migration IBA WITH/FROM; this is expected and not circular.

Round 6 of projects/INVOLVED_IN_PRECOMPOSITION.md (2026-11-10): the two GO:1902742 MODIFY replacements now use GO:0043065 positive regulation of apoptotic process instead of the precomposed GO:1904747 positive regulation of apoptotic process involved in development, with decomposed_into.context_dropped. The sign correction (the gene promotes death from the engulfing cell rather than taking part in the dying cell's program) is unchanged; only the developmental context is dropped. Earlier mentions of GO:1904747 above are superseded.