ced-12 (C. elegans) curation notes

UniProt: Q8STE5 (CED12_CAEEL), 731 aa. ELMO orthologue: ARM repeats, ELMO domain, C-terminal PH domain, proline-rich
SH3-binding motif. UniProt gives no PANTHER family; none is asserted here.

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

Identity and pathway

• ced-12 was found as a new engulfment gene that is also needed to clear necrotic corpses
  PMID:11146658.
• Three 2001 papers cloned ced-12 and placed it with ced-2 (CrkII), ced-5 (DOCK180) and ced-10 (Rac)
  PMID:11595183
  PMID:11703939
  PMID:11703940.
• CED-12 acts in the engulfing cell PMID:11703939.

Molecular function

• ELMO/CED-12 binds DOCK180/CED-5 and the complex stimulates Rac exchange
  PMID:11595183.
• Mechanism: the ELMO PH domain binds the DOCK180-Rac complex in trans
  PMID:15247908.
  So CED-12 is a GEF activator (GO:0160124), not a GEF itself.
• Binding to CED-5 uses the CED-12 SH3-binding motif and the CED-5 SH3 domain
  PMID:11703939
  PMID:11703939.
  The GOA row "proline-rich region binding" therefore has the orientation reversed; SH3 domain binding is the right term.
• ARM repeats bind active MIG-2/RhoG PMID:15620647.
• PH domain binds phosphoinositides in vitro PMID:21490059;
  UniProt also lists PtdIns4P and PtdIns(3,4,5)P3 from the same paper (not visible in the abstract).

Processes

• Engulfment of apoptotic cells (core) and necrotic corpses.
• Distal tip cell migration: MOM-5/Frizzled acts through the CED-2/5/12 branch
  PMID:20126385.
• Spindle orientation is NOT routed through CED-2/5/12 in that paper
  PMID:20126385.
  The spindle and left/right IGI rows for ced-12 were removed on this basis.
• Upstream regulators: MTM-1 PMID:21490059;
  PSR-1 (proposed PS receptor) PMID:14645848.

Apoptosis rows (clearance-defect background)

• PMID:24225442 (CED-8 paper, full text) uses ced-12(n3261) only as an engulfment-defective background
  PMID:24225442.
  The GO:1902742 rows were changed to GO:1904747, following ced-1/ced-6/ced-7.
• Support for engulfment genes promoting death: PMID:11449278,
  PMID:11449278,
  PMID:11449279.
  Reddien's abstract defines its engulfment genes as an enumerated set that includes ced-12, and states
  PMID:11449278.
  The GO:1904747 rows rest on that reading.

Not read / limits

• Abstract-only: PMID:11146658, 11595183, 11703939, 11703940, 14645848, 14688791, 15247908, 15620647, 15744306,
  21490059, 11449278, 11449279.
• PMID:14688791 (mig-23 NDPase paper) does not mention ced-12 in the abstract; its ced-12 rows were kept as non-core.
• PMID:26292279 (CED-12 and UNC-5 in DTC steering, cited by UniProt) is not cached; it was not used as evidence.

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.