ced-5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000132 establishment of mitotic spindle orientation	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MARK AS OVER ANNOTATED	Summary: Establishment of mitotic spindle orientation (IGI with mom-5, Cabello et al. 2010). Reason: In the full text, ABar spindle orientation needs MOM-5/Frizzled, GSK-3 and the beta-catenin WRM-1, and CED-10/Rac. The authors state that apart from ced-10 none of the ced genes had a strong spindle defect, and they conclude that the link to CED-10 for spindles probably does not go through CED-2/5/12. Spindle defects were seen only in a small fraction of ced-1; ced-5 double mutants. Unlike engulfment and distal tip cell migration, spindle orientation is not a demonstrated ced-5 function. Supporting Evidence: PMID:20126385 neither apr-1 nor any of the other ced genes showed a strong defect, suggesting that the link to CED-10 may not occur through CED-2/5/12 as is the case for engulfment and DTC migration PMID:20126385 we did observe spindle defects in a small fraction of ced-1; ced-5 double mutants
GO:0000132 establishment of mitotic spindle orientation	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MARK AS OVER ANNOTATED	Summary: Establishment of mitotic spindle orientation (IGI with ced-12, Cabello et al. 2010). Reason: Same paper as the mom-5 row. The authors found no strong spindle defect in ced mutants other than ced-10 and suggest that the Wnt signal reaches CED-10 for spindle orientation by a route other than CED-2/5/12. A rare defect in double mutants is too weak to assign this process to CED-5. Supporting Evidence: PMID:20126385 neither apr-1 nor any of the other ced genes showed a strong defect, suggesting that the link to CED-10 may not occur through CED-2/5/12 as is the case for engulfment and DTC migration
GO:0005085 guanyl-nucleotide exchange factor activity	IBA GO_REF:0000033	ACCEPT	Summary: Guanyl-nucleotide exchange factor activity, inherited from the DOCK family node. Reason: GEF activity of the DHR-2 domain is the defining, ancestral activity of the DOCK family, and CED-5 is the direct orthologue of DOCK180 and Myoblast City with a full DHR-2 domain. Worm genetics place CED-5 with CED-12/ELMO upstream of CED-10/Rac, and the CED-12/ELMO-CED-5/DOCK180 complex is described as the GEF for CED-10. This is the core molecular function. GO now has no Rac-specific GEF term (GO:0030676 is obsolete), so this is the most specific available term. Supporting Evidence: PMID:20126385 the CED-12/ELMO-CED-5/DOCK180 complex, which acts as a GEF to activate CED-10/Rac PMID:11595183 CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements
GO:0005085 guanyl-nucleotide exchange factor activity	IEA GO_REF:0000002	ACCEPT	Summary: Guanyl-nucleotide exchange factor activity, from the InterPro DOCK family signature. Reason: The DOCK family signature (IPR026791) maps correctly to GEF activity. CED-5 has the catalytic DHR-2 (DOCKER) domain, and the genetic and biochemical data in worms and mammals support the activity. Supporting Evidence: PMID:9548255 encodes a protein that is similar to the human protein DOCK180 and the Drosophila melanogaster protein Myoblast City (MBC)
GO:0005085 guanyl-nucleotide exchange factor activity	ISS PMID:9548255 C. elegans phagocytosis and cell-migration protein CED-5 is ...	ACCEPT	Summary: Guanyl-nucleotide exchange factor activity, by similarity to human DOCK180 (Wu and Horvitz 1998). Reason: The paper identifies CED-5 as the DOCK180 orthologue, and human DOCK180 rescues the ced-5 migration defect in worms, showing functional conservation. DOCK180 is an established Rac GEF. Accepted as core function. Supporting Evidence: PMID:9548255 The expression of human DOCK180 in C. elegans rescued the cell-migration defect of a ced-5 mutant
GO:0005515 protein binding	IPI PMID:10707082 CED-2/CrkII and CED-10/Rac control phagocytosis and cell mig...	REMOVE	Summary: Protein binding with CED-2/CrkII (Reddien and Horvitz 2000). Reason: Bare protein binding says nothing about function. The CED-2-CED-5 interaction is real and is captured more informatively by the CED-2 SH3 domain binding row, the guanyl-nucleotide exchange factor complex annotation and the GEF activity. Removal does not mean the interaction is false. Supporting Evidence: PMID:10707082 that CED-2 and CED-5 physically interact
GO:0005515 protein binding	IPI PMID:11595183 CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway...	REMOVE	Summary: Protein binding with CED-12/ELMO (Gumienny et al. 2001). Reason: Bare protein binding is uninformative. CED-12/ELMO binds CED-5 directly to form the bipartite Rac GEF; that relationship is captured by the GEF activity and the guanyl-nucleotide exchange factor complex annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:11595183 CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements
GO:0005515 protein binding	IPI PMID:11703940 C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pa...	REMOVE	Summary: Protein binding with CED-12 (Wu et al. 2001). Reason: Bare protein binding is uninformative. The CED-12 interaction and the CED-2/CED-5/CED-12 ternary complex are captured by the guanyl-nucleotide exchange factor complex annotation from the same paper. Removal does not mean the interaction is false. Supporting Evidence: PMID:11703940 CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro
GO:0005515 protein binding	IPI PMID:21616056 Crystal structure of the cell corpse engulfment protein CED-...	REMOVE	Summary: Protein binding with CED-2 via the CED-5 N-terminal region (Kang et al. 2011). Reason: Bare protein binding is uninformative. The paper maps a CED-2 contact to the N-terminal region of CED-5, but there is no GO term for that specific interaction that would add meaning beyond the complex membership already annotated. Removal does not mean the interaction is false. Supporting Evidence: PMID:21616056 CED-2 was found to interact with the N-terminal region of CED-5
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasm, inherited from the DOCK family node. Reason: DOCK proteins are soluble cytoplasmic proteins without transmembrane segments that are recruited to membranes to act on Rac. Cytoplasm is correct, if general.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Cytoplasm, from the UniProt subcellular location mapping. Reason: Consistent with the DOCK family and with CED-5 lacking any membrane-spanning segment.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Plasma membrane as the site of activity, inherited from the DOCK family node. Reason: DOCK GEFs act on Rac at the inner face of the plasma membrane, recruited through their DHR-1 lipid binding domain and partners. The worm model places the CED-2/CED-5/CED-12 complex at the plasma membrane of engulfing and migrating cells, where it activates CED-10. Supporting Evidence: PMID:11703940 We propose that the formation and localization of a CED-2-CED-5-CED-12 ternary complex to the plasma membrane activates CED-10
GO:0005886 plasma membrane	TAS PMID:10707082 CED-2/CrkII and CED-10/Rac control phagocytosis and cell mig...	ACCEPT	Summary: Plasma membrane, traceable author statement (Reddien and Horvitz 2000). Reason: The abstract proposes that CED-2 and CED-5 activate CED-10/Rac to control polarized extension of the cell surface, which implies action at the plasma membrane. No direct localization data for CED-5 are in the abstract, but the location agrees with the DOCK family IBA and the later ternary-complex model. Supporting Evidence: PMID:10707082 We propose that CED-2/CrkII and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces
GO:0007264 small GTPase-mediated signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: Small GTPase-mediated signal transduction, from the InterPro DOCK family signature. Reason: CED-5 activates CED-10/Rac within a signalling pathway that links engulfment and guidance cues to the actin cytoskeleton. The term is broad but correct. Supporting Evidence: PMID:10707082 We propose that CED-2/CrkII and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces
GO:0007369 gastrulation	IGI PMID:21527776 Overcoming redundancy: an RNAi enhancer screen for morphogen...	KEEP AS NON CORE	Summary: Gastrulation (IGI with hmr-1/cadherin, Sullivan-Brown et al. 2011 RNAi enhancer screen). Reason: In the full text, ced-5 null embryos internalize the endoderm precursors normally on their own, but ced-5 acts redundantly with hmr-1 (cadherin), and ced-5(n1812) is a strong sensitized background in which RNAi of many genes causes gastrulation defects. This supports a real but partially redundant contribution to gastrulation cell movements, plausibly through Rac-driven cytoskeletal change. It is not a core function. Supporting Evidence: PMID:21527776 ced-5, which encodes a DOCK180-like guanine exchange factor for Rac (Wu and Horvitz 1998) and hmr-1, which encodes a classical cadherin (Costa et al. 1998), function redundantly in C. elegans gastrulation PMID:21527776 We confirmed that Ea/Ep internalize successfully in a likely null allele of ced-5, n1812
GO:0007520 myoblast fusion	IBA GO_REF:0000033	REMOVE	Summary: Myoblast fusion, inherited from a DOCK-A node seeded by Drosophila Myoblast City and a zebrafish gene. Reason: CED-5 sits correctly inside the DOCK180/Myoblast City clade, so the node placement is not in question for the GEF activity. The problem is the process. Myoblast fusion builds multinucleate muscle fibers in flies and vertebrates, but C. elegans body wall muscle cells are mononucleate and do not form by myoblast fusion, so the process does not occur in the target organism. The ancestral GEF activity was inherited; a lineage-specific use of it in muscle formation was not. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: FB:FBgn0015513 · mbc SUPPORTS SOURCE BUT NOT TARGET Myoblast City is required for myoblast fusion in Drosophila, but nematode body wall muscle does not form by myoblast fusion. PANTHER:PTN000594048 · PTN000594048 SUPPORTS SOURCE BUT NOT TARGET The DOCK-A node is appropriate for GEF activity and cell migration; the process term reflects muscle biology of flies and vertebrates rather than an ancestral property. Supporting Evidence: PMID:9548255 encodes a protein that is similar to the human protein DOCK180 and the Drosophila melanogaster protein Myoblast City (MBC)
GO:0016477 cell migration	IBA GO_REF:0000033	ACCEPT	Summary: Cell migration, inherited from the DOCK-A node. Reason: Cell migration is a conserved function of DOCK-A proteins, and ced-5 itself has experimental evidence for distal tip cell migration (it appears among the sources, as expected when the target has its own experimental annotation). Supporting Evidence: PMID:9548255 ced-5 mutants are defective not only in the engulfment of cell corpses but also in the migrations of two specific gonadal cells, the distal tip cells
GO:0016477 cell migration	IMP PMID:9548255 C. elegans phagocytosis and cell-migration protein CED-5 is ...	ACCEPT	Summary: Cell migration (IMP, Wu and Horvitz 1998). Reason: ced-5 mutants are defective in the migration of the two gonadal distal tip cells, and human DOCK180 rescues this defect. Cell migration is correct; the more specific distal tip cell migration term is proposed through the Cabello et al. 2010 rows and the core functions. Supporting Evidence: PMID:9548255 ced-5 mutants are defective not only in the engulfment of cell corpses but also in the migrations of two specific gonadal cells, the distal tip cells PMID:9548255 The expression of human DOCK180 in C. elegans rescued the cell-migration defect of a ced-5 mutant
GO:0017124 SH3 domain binding	IPI PMID:10707082 CED-2/CrkII and CED-10/Rac control phagocytosis and cell mig...	KEEP AS NON CORE	Summary: SH3 domain binding with CED-2/CrkII (Reddien and Horvitz 2000). Reason: CED-2 is an SH2/SH3 adaptor, and its first SH3 domain binds a PXXP motif of CED-5, as confirmed by the CED-2 F125G mutation that disrupts this contact. The binding is real, but Kang et al. found that this PXXP contact is not needed for CED-2 rescuing activity, and an N-terminal CED-5 region also binds CED-2. The interaction is part of complex assembly, not the core activity. Supporting Evidence: PMID:10707082 that CED-2 and CED-5 physically interact PMID:21616056 A CED-2 point mutation (F125G) disrupting its interaction with the PXXP motif of CED-5 did not affect its rescuing activity
GO:0017124 SH3 domain binding	IPI PMID:11703939 The C. elegans PH domain protein CED-12 regulates cytoskelet...	MODIFY	Summary: SH3 domain binding with CED-12 (Zhou et al. 2001). Reason: The direction is reversed. In this paper CED-12 carries the SH3-binding (proline-rich) motif and CED-5 carries the SH3 domain, so CED-5 binds a proline-rich region of CED-12 rather than an SH3 domain. The matching term for CED-5 is proline-rich region binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:11703939 ced-12 encodes a protein with a pleckstrin homology (PH) domain and an SH3 binding motif PMID:11703939 interacts physically with CED-5, which contains an SH3 domain
GO:0019899 enzyme binding	IPI PMID:14645848 Cell corpse engulfment mediated by C. elegans phosphatidylse...	MARK AS OVER ANNOTATED	Summary: Enzyme binding with PSR-1 (Wang et al. 2003). Reason: The abstract (full text not available here) reports a possible direct interaction between PSR-1 and CED-5/CED-12. Calling this enzyme binding is uninformative, because the partner's enzymatic activity is not what the interaction is about; PSR-1 was studied as a putative phosphatidylserine receptor upstream of CED-5. The interaction is not disputed here, but the term does not describe a CED-5 function. Supporting Evidence: PMID:14645848 possibly through direct interaction with CED-5 and CED-12
GO:0030695 GTPase regulator activity	TAS PMID:9548255 C. elegans phagocytosis and cell-migration protein CED-5 is ...	MODIFY	Summary: GTPase regulator activity (TAS, Wu and Horvitz 1998). Reason: Correct but too general. CED-5 regulates the Rac GTPase CED-10 as a guanyl-nucleotide exchange factor, for which a specific term exists. Proposed replacements: guanyl-nucleotide exchange factor activity Supporting Evidence: PMID:11595183 CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements
GO:0031267 small GTPase binding	IBA GO_REF:0000033	ACCEPT	Summary: Small GTPase binding, inherited from the DOCK family node. Reason: DOCK GEFs bind their nucleotide-free Rac substrate through the DHR-2 domain as part of the exchange reaction. This is a mechanistic part of the GEF activity, and CED-5 retains the DHR-2 domain. Supporting Evidence: PMID:10707082 We propose that CED-2/CrkII and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces
GO:0032045 guanyl-nucleotide exchange factor complex	IDA PMID:11703940 C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pa...	ACCEPT	Summary: Guanyl-nucleotide exchange factor complex (IDA, Wu et al. 2001). Reason: CED-5 forms a complex with CED-12 and a ternary complex with CED-2, which activates CED-10/Rac. In mammals the orthologous DOCK180-ELMO complex is the functional bipartite Rac GEF. Supporting Evidence: PMID:11703940 CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro PMID:11595183 CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements
GO:0043652 engulfment of apoptotic cell	IMP PMID:1936965 Genes required for the engulfment of cell corpses during pro...	ACCEPT	Summary: Engulfment of apoptotic cell (IMP, Ellis et al. 1991). Reason: The founding genetic study identified ced-5 as an engulfment gene, with electron microscopy showing that engulfment is prevented in the mutants. Core process. Supporting Evidence: PMID:1936965 We have identified five new genes that play a role in this process: ced-5, ced-6, ced-7, ced-8 and ced-10 PMID:1936965 Electron microscopic studies reveal that mutations in each of these genes prevent engulfment
GO:0043652 engulfment of apoptotic cell	IMP PMID:9548255 C. elegans phagocytosis and cell-migration protein CED-5 is ...	ACCEPT	Summary: Engulfment of apoptotic cell (IMP, Wu and Horvitz 1998). Reason: ced-5 is required for corpse engulfment and acts in the engulfing cell, where it is proposed to drive extension of the engulfing cell surface around the corpse. Core process. Supporting Evidence: PMID:9548255 We present evidence that ced-5 functions in engulfing cells during the engulfment of cell corpses
GO:0044877 protein-containing complex binding	IPI PMID:11703940 C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pa...	MARK AS OVER ANNOTATED	Summary: Protein-containing complex binding with CED-12 (Wu et al. 2001). Reason: CED-5 is a subunit of the CED-2/CED-5/CED-12 complex rather than a protein that binds a pre-formed complex. Membership is captured by the guanyl-nucleotide exchange factor complex annotation from the same paper, so this term adds no functional information. Supporting Evidence: PMID:11703940 CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro
GO:0044877 protein-containing complex binding	IPI PMID:11703940 C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pa...	MARK AS OVER ANNOTATED	Summary: Protein-containing complex binding with CED-2 (Wu et al. 2001). Reason: As for the CED-12 row, CED-5 is a member of the ternary complex, which is captured by the guanyl-nucleotide exchange factor complex annotation. Complex binding does not describe a CED-5 activity. Supporting Evidence: PMID:11703940 CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro
GO:0070986 left/right axis specification	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MARK AS OVER ANNOTATED	Summary: Left/right axis specification (IGI with mom-5, Cabello et al. 2010). Reason: The left/right readout in this paper is the orientation of the ABar spindle. That depends on MOM-5, GSK-3, WRM-1/beta-catenin and CED-10, and the authors state that the other ced genes showed no strong defect and that CED-2/5/12 is probably not the route. ced-5 shows at most rare spindle defects in double mutants with ced-1. Supporting Evidence: PMID:20126385 neither apr-1 nor any of the other ced genes showed a strong defect, suggesting that the link to CED-10 may not occur through CED-2/5/12 as is the case for engulfment and DTC migration
GO:0070986 left/right axis specification	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MARK AS OVER ANNOTATED	Summary: Left/right axis specification (IGI with ced-12, Cabello et al. 2010). Reason: Same reasoning as the mom-5 row. Neither ced-5 nor ced-12 has a strong ABar spindle defect in this paper, so left/right axis specification is not supported as a ced-5 function. Supporting Evidence: PMID:20126385 neither apr-1 nor any of the other ced genes showed a strong defect, suggesting that the link to CED-10 may not occur through CED-2/5/12 as is the case for engulfment and DTC migration PMID:20126385 we did observe spindle defects in a small fraction of ced-1; ced-5 double mutants
GO:1901076 positive regulation of engulfment of apoptotic cell	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of engulfment of apoptotic cell (IGI with mom-5, Cabello et al. 2010). Reason: CED-5 is part of the engulfment machinery itself, the GEF that activates CED-10/Rac in the engulfing cell, not an outside regulator of engulfment. In this paper ced-5 single mutants fail to engulf about 70% of first-wave embryonic corpses, and MOM-5 acts through the CED-2/CED-5/CED-12 GEF complex. The direct process term is the accurate one. Proposed replacements: engulfment of apoptotic cell Supporting Evidence: PMID:20126385 Approximately 70% of cells dying in the first wave of embryonic apoptosis failed to be engulfed in mom-5, ced-5, or ced-10 single mutants PMID:20126385 The epistatic and bypass experiments indeed indicate that MOM-5/Fz activates CED-10/Rac through the GEF complex CED-2, CED-5, CED-12
GO:1901076 positive regulation of engulfment of apoptotic cell	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of engulfment of apoptotic cell (IGI with ced-12, Cabello et al. 2010). Reason: CED-5 and CED-12 together form the GEF that carries out the engulfment step of activating CED-10/Rac. They do engulfment rather than regulate it, so the direct process term is the accurate one. Proposed replacements: engulfment of apoptotic cell Supporting Evidence: PMID:20126385 The epistatic and bypass experiments indeed indicate that MOM-5/Fz activates CED-10/Rac through the GEF complex CED-2, CED-5, CED-12
GO:1901076 positive regulation of engulfment of apoptotic cell	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of engulfment of apoptotic cell (IGI with ced-1, Cabello et al. 2010). Reason: The ced-1; ced-5 double mutant analysis in this paper concerns the engulfment process itself, in which CED-5 is a core component. The direct process term is the accurate one. Proposed replacements: engulfment of apoptotic cell Supporting Evidence: PMID:20126385 the additive engulfment defect in ced-1; ced-5 double mutants is quite pronounced at later time points
GO:1901076 positive regulation of engulfment of apoptotic cell	IMP PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of engulfment of apoptotic cell (IMP, Cabello et al. 2010). Reason: The ced-5 single mutant fails to engulf most first-wave embryonic corpses and germ cell corpses persist. This is a direct requirement for engulfment by a core component, so the direct process term is the accurate one. Proposed replacements: engulfment of apoptotic cell Supporting Evidence: PMID:20126385 Approximately 70% of cells dying in the first wave of embryonic apoptosis failed to be engulfed in mom-5, ced-5, or ced-10 single mutants
GO:1902742 apoptotic process involved in development	IGI PMID:24225442 Caspase-mediated activation of Caenorhabditis elegans CED-8 ...	MODIFY	Summary: Apoptotic process involved in development (IGI with ced-8, Chen et al. 2013, CED-8 paper). Reason: In the full text, ced-5(n1812) is used only as an engulfment-defective background in which corpses persist and can be counted; the paper tests ced-8, so this is a clearance readout, not evidence that CED-5 takes part in the dying cell's apoptotic program. The positive regulation term is supported instead by Reddien et al. 2001, whose abstract defines the engulfment genes it studies as ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 and states that mutations in engulfment genes alone allow some cells that would normally die to survive, and by Hoeppner et al. 2001. ced-5 is in that enumerated set, and engulfment genes act from the engulfing cell to promote death, which is positive regulation rather than participation. The replacement is GO:0043065 positive regulation of apoptotic process, without the developmental context of its precomposed child GO:1904747. Proposed replacements: positive regulation of apoptotic process Context of precomposed term: context dropped The replacement is unfolded from GO:1904747 positive regulation of apoptotic process involved in development to GO:0043065 (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6); the sign correction (regulation, not participation) is unchanged. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene. Supporting Evidence: PMID:24225442 ced-8(n1891) markedly enhanced the cell corpse engulfment defect of the ced-2, ced-5 or ced-12 mutants PMID:11449278 the engulfment of dying cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 PMID:11449278 mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die PMID:11449278 mutations in engulfment genes enhance the frequency of this cell survival PMID:11449279 genes that mediate corpse removal can also function to actively kill cells
GO:1902742 apoptotic process involved in development	IMP PMID:22801495 Programmed elimination of cells by caspase-independent cell ...	REMOVE	Summary: Apoptotic process involved in development (IMP, Denning et al. 2012, cell extrusion paper). Reason: In the full text, ced-5 mutants serve as the engulfment-defective comparison. Their unengulfed "floaters" still undergo CED-3-mediated apoptosis and show apoptotic features; they detach only because engulfing cells cannot take them in. Cell shedding in caspase mutants did not require engulfment genes. Nothing in the paper shows ced-5 acting in, or promoting, apoptosis; the ced-5 phenotype here is a clearance defect, which is already captured by engulfment of apoptotic cell. Any positive-regulation claim is handled on the CED-8 paper rows with its own sources. Supporting Evidence: PMID:22801495 cells that undergo CED-3-mediated apoptosis and detach from the embryo because they cannot be internalized by engulfing cells PMID:22801495 These apoptotic features were present in ced-5 floaters
GO:1902742 apoptotic process involved in development	IMP PMID:24225442 Caspase-mediated activation of Caenorhabditis elegans CED-8 ...	MODIFY	Summary: Apoptotic process involved in development (IMP, Chen et al. 2013, CED-8 paper). Reason: In the full text, ced-5(n1812) is used only as an engulfment-defective background in which corpses persist and can be counted; the paper tests ced-8, so this is a clearance readout, not evidence that CED-5 takes part in the dying cell's apoptotic program. The positive regulation term is supported instead by Reddien et al. 2001, whose abstract defines the engulfment genes it studies as ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 and states that mutations in engulfment genes alone allow some cells that would normally die to survive, and by Hoeppner et al. 2001. ced-5 is in that enumerated set, and engulfment genes act from the engulfing cell to promote death, which is positive regulation rather than participation. The replacement is GO:0043065 positive regulation of apoptotic process, without the developmental context of its precomposed child GO:1904747. Proposed replacements: positive regulation of apoptotic process Context of precomposed term: context dropped The replacement is unfolded from GO:1904747 positive regulation of apoptotic process involved in development to GO:0043065 (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6); the sign correction (regulation, not participation) is unchanged. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene. Supporting Evidence: PMID:24225442 ced-8(n1891) markedly enhanced the cell corpse engulfment defect of the ced-2, ced-5 or ced-12 mutants PMID:11449278 the engulfment of dying cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 PMID:11449278 mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die PMID:11449278 mutations in engulfment genes enhance the frequency of this cell survival PMID:11449279 genes that mediate corpse removal can also function to actively kill cells
GO:1903356 positive regulation of distal tip cell migration	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of distal tip cell migration (IGI with mom-5, Cabello et al. 2010). Reason: The paper shows that MOM-5/Frizzled acts through CED-5 and CED-10 in distal tip cell migration, as overexpression of CED-5 or CED-10 suppresses the mom-5 migration defect. CED-5 is part of the migration machinery, the GEF that activates CED-10/Rac to remodel the cytoskeleton of the migrating cell, not an outside regulator. The direct process term, distal tip cell migration, is the accurate one. Proposed replacements: distal tip cell migration Supporting Evidence: PMID:20126385 overexpression of both CED-5 and CED-10 significantly suppressed the mom-5 DTC migration defect
GO:1903356 positive regulation of distal tip cell migration	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of distal tip cell migration (IGI with ced-12, Cabello et al. 2010). Reason: CED-5 with CED-12 forms the GEF that drives distal tip cell migration through CED-10/Rac. Mutations in this branch cause aberrant migration directly, so the direct process term is the accurate one. Proposed replacements: distal tip cell migration Supporting Evidence: PMID:20126385 Mutations in this second pathway not only result in defects in cell corpse engulfment but also result in aberrant distal tip cell (DTC) migration
GO:1903356 positive regulation of distal tip cell migration	IGI PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of distal tip cell migration (IGI with ced-1, Cabello et al. 2010). Reason: The ced-1 interaction itself is weak evidence, since the paper finds that the CED-1/6/7 pathway plays at most a minor role in distal tip cell migration. But ced-5 has a well-established direct requirement in this migration, so the row is kept with the direct process term rather than the regulation term. Proposed replacements: distal tip cell migration Supporting Evidence: PMID:20126385 we found that the CED-1/6/7 pathway appears to play at most a minor role, if any, in this process PMID:9548255 ced-5 mutants are defective not only in the engulfment of cell corpses but also in the migrations of two specific gonadal cells, the distal tip cells
GO:1903356 positive regulation of distal tip cell migration	IMP PMID:20126385 The Wnt pathway controls cell death engulfment, spindle orie...	MODIFY	Summary: Positive regulation of distal tip cell migration (IMP, Cabello et al. 2010). Reason: CED-5 is directly required for distal tip cell migration as a core component of the Rac-activating machinery. The direct process term is the accurate one. Proposed replacements: distal tip cell migration Supporting Evidence: PMID:20126385 Mutations in this second pathway not only result in defects in cell corpse engulfment but also result in aberrant distal tip cell (DTC) migration

Gene Description

Existing Annotations Review

Core Functions

DOCK-family guanine nucleotide exchange factor that, in a complex with CED-12/ELMO and the adaptor CED-2/CrkII, activates the Rac GTPase CED-10 at the plasma membrane of engulfing cells, driving the actin reorganization and surface extension needed to engulf apoptotic cell corpses.

The same CED-5 GEF activity on CED-10/Rac drives the guided migration of the gonadal distal tip cells, downstream of MOM-5/Frizzled signalling.

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WormBase

WormBase gene description for ced-5 (worm)

📚 Additional Documentation

Notes

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