ced-5 (C. elegans) curation notes

UniProtKB:G5EEN3 (unreviewed TrEMBL entry, 1781 aa), WormBase WBGene00000419, C02F4.1.

Deep-research providers were not available for this review. These notes are a manual synthesis from the
cached publications in publications/ (most are abstract-only; PMID:20126385, PMID:21527776,
PMID:22801495 and PMID:24225442 have full text cached).

Identity and domains

• DOCK family (UniProt: "Belongs to the DOCK family"; InterPro IPR026791 DOCK, IPR027007 DOCK-type C2 / DHR-1,
  IPR027357 DOCKER / DHR-2, IPR001452 SH3; PANTHER PTHR45653:SF10 "MYOBLAST CITY, ISOFORM B").
• Orthologue of human DOCK180 and fly Myoblast City PMID:9548255. Human DOCK180 rescues
  ced-5 PMID:9548255.

Molecular function

• Bipartite Rac GEF with CED-12/ELMO PMID:11595183; PMID:20126385.
• Ternary complex with CED-2/CrkII PMID:11703940. CED-2 binds both a PXXP motif and the N-terminal region of CED-5; the PXXP
  contact is dispensable for rescue PMID:21616056.
• The CED-5 SH3 domain binds the proline-rich motif of CED-12 PMID:11703939, so the SH3 domain binding IPI with CED-12 is reversed for CED-5; changed to
  proline-rich region binding.
• No direct in vitro exchange assay on CED-10 with worm CED-5 found in the cached papers; the GEF activity
  rests on orthology plus the mammalian ELMO/DOCK180 biochemistry and worm epistasis.
• GO:0030676 (Rac GEF activity) is obsolete; GO:0005085 is the most specific valid MF term.

Processes

• Engulfment of apoptotic cells, acting in engulfing cells PMID:9548255; founding genetics PMID:1936965.
• Distal tip cell migration PMID:9548255.
• Wnt input (Cabello 2010, full text): MOM-5/Frizzled, GSK-3 and APR-1 act through CED-2/5/12 in engulfment and
  DTC migration PMID:20126385; PMID:20126385. ced-5 single mutants fail to engulf ~70% of
  first-wave embryonic corpses PMID:20126385.
• Spindle orientation / left-right: NOT through CED-2/5/12 per the same paper PMID:20126385; only rare defects in ced-1; ced-5 doubles. So,
  unlike engulfment and DTC migration, the spindle and L/R rows are over-annotations for ced-5 too.
• Gastrulation: partially redundant with hmr-1 PMID:21527776; ced-5 alone gastrulates normally. Non-core.
• Promotion of cell death by engulfment: PMID:11449278; PMID:11449279. Reddien's abstract defines its engulfment genes as an enumerated set that includes ced-5, and states
  PMID:11449278. The GO:1904747 rows rest on that reading (both papers abstract-only).

Clearance-defect / background-genotype rows

• PMID:24225442 (CED-8): ced-5(n1812) used as engulfment background PMID:24225442. GO:1902742 rows MODIFY to
  GO:1904747, per the APOPTOSIS project rule.
• PMID:22801495 (cell extrusion, full text): ced-5 is the engulfment-defective comparison; its floaters still
  die by CED-3-mediated apoptosis PMID:22801495. No support for ced-5 in apoptosis;
  REMOVE.

IBA notes

• Myoblast fusion IBA (PTN000594048, seeded by fly mbc and a zebrafish gene): CED-5 is correctly in the DOCK-A
  clade, but C. elegans body wall muscle cells are mononucleate and do not arise by myoblast fusion. REMOVE
  with propagation_review (LINEAGE_OR_TAXON_MISMATCH).
• ced-5 (WB:WBGene00000419) appears among the sources of its own cell migration IBA; that is expected, 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.