Megf10

Summary: C1q complex binding (transferred from human MEGF10, Iram et al. 2016).

Reason: Iram et al. 2016 showed high-affinity C1q binding by Megf10 and used mouse knockouts. This is ligand recognition for the core engulfment function. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: C1q complex binding (transferred from human MEGF10, Iram et al. 2016).

Reason: Iram et al. 2016 showed high-affinity C1q binding by Megf10 and used mouse knockouts. This is ligand recognition for the core engulfment function. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: Phagocytic cup (IBA).

Reason: Consistent with direct observation of Megf10 at phagocytic cups.

Summary: Megf10 accumulates around engulfed apoptotic nuclei and at phagocytic cups (Wu et al. 2009).

Reason: IDA. The full text shows MEGF10::GFP at vacuoles holding apoptotic nuclei and at what appear to be phagocytic cups.

Summary: Phagocytic cup (electronic).

Reason: Consistent with the IDA.

Summary: Phagocytic cup (ISO from human).

Reason: Consistent with the mouse IDA. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: Scavenger receptor activity (IBA, PTN009076277 in PTHR24035; sources MEGF10 and ced-1).

Reason: Core MF of the CED-1/Draper/MEGF10 engulfment receptors. The UniProt PANTHER cross-reference (PTHR24052) differs from the family that carries this node; see projects/PANTHER_FAMILY_ASSIGNMENT_DISCREPANCIES.md.

Summary: Scavenger receptor activity (Ensembl Compara from human).

Reason: Core MF. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: Scavenger receptor activity (ISO, Iram et al. 2016).

Reason: Core MF. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: Notch binding (IBA/IEA/ISO).

Reason: Based on co-immunoprecipitation of the Megf10 and Notch1 intracellular domains. Megf10 regulates satellite-cell and myoblast proliferation and differentiation, partly through Notch signaling. These roles are real but separate from the conserved engulfment-receptor function, so they are kept as non-core.

Summary: Notch binding (IBA/IEA/ISO).

Reason: Based on co-immunoprecipitation of the Megf10 and Notch1 intracellular domains. Megf10 regulates satellite-cell and myoblast proliferation and differentiation, partly through Notch signaling. These roles are real but separate from the conserved engulfment-receptor function, so they are kept as non-core.

Summary: Megf10 and Notch1 co-immunoprecipitate via their intracellular domains (Saha et al. 2017).

Reason: IPI. The interaction is reported between cytoplasmic domains and is relevant to muscle phenotypes. Megf10 regulates satellite-cell and myoblast proliferation and differentiation, partly through Notch signaling. These roles are real but separate from the conserved engulfment-receptor function, so they are kept as non-core.

Summary: Notch binding (IBA/IEA/ISO).

Reason: Based on co-immunoprecipitation of the Megf10 and Notch1 intracellular domains. Megf10 regulates satellite-cell and myoblast proliferation and differentiation, partly through Notch signaling. These roles are real but separate from the conserved engulfment-receptor function, so they are kept as non-core.

Summary: Plasma membrane.

Reason: Megf10 is a single-pass type I cell-surface receptor.

Summary: Plasma membrane (IDA, Suzuki and Nakayama 2007).

Reason: MEGF10 shows a surface adhesion pattern that AP2 mirrors at the membrane. The location is correct for a transmembrane receptor.

Summary: Plasma membrane (IDA, Saha et al. 2017).

Reason: IDA from Saha et al. 2017; the cached record is abstract-only, so the localization data cannot be checked here. Plasma membrane is the established location of this type I receptor, shown by surface biotinylation of MEGF10. Deferring to the curator.

Summary: Plasma membrane.

Reason: Megf10 is a single-pass type I cell-surface receptor.

Summary: Plasma membrane.

Reason: Megf10 is a single-pass type I cell-surface receptor.

Summary: Satellite cell activation (IMP, Holterman et al. 2007).

Reason: IMP from PMID:18056409. No cited study assays the quiescence-to-activation transition itself. Holterman et al. 2007 describe Megf10 as a marker of quiescent satellite cells and show that silencing it in already-activated satellite cells reduces their number through myogenin activation and precocious differentiation, which is a differentiation phenotype rather than a failure to activate. Logan et al. 2011 report expression in activated satellite cells, which is not participation in activation. The proliferation and differentiation terms already capture what was shown.

Summary: Satellite cell differentiation (IEA/ISO).

Reason: Electronic annotation. Silencing Megf10 causes precocious differentiation of satellite cells and overexpression inhibits differentiation, so Megf10 restrains satellite-cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Satellite cell differentiation (IMP, Holterman et al. 2007).

Reason: IMP from PMID:18056409. Silencing Megf10 causes precocious differentiation of satellite cells and overexpression inhibits differentiation, so Megf10 restrains satellite-cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Satellite cell differentiation (IEA/ISO).

Reason: Transferred from human MEGF10. Silencing Megf10 causes precocious differentiation of satellite cells and overexpression inhibits differentiation, so Megf10 restrains satellite-cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Satellite cell proliferation (IDA, Holterman et al. 2007).

Reason: IDA from PMID:18056409. Megf10 overexpression enhances myoblast proliferation and silencing depletes the satellite-cell pool, supporting a role in sustaining satellite-cell proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Vesicle-mediated transport (inferred from scavenger receptor activity).

Reason: Vesicle-mediated transport is a correct but uninformative parent of receptor-mediated engulfment. The informative process, engulfment of apoptotic cell (GO:0043652), is already annotated, so this broad inference adds no information.

Summary: Positive regulation of cell-cell adhesion, transferred from human MEGF10.

Reason: The human source annotation (IMP, PMID:31267131) is UNDECIDED in the human review because the cached abstract does not mention cell-cell adhesion. The transferred annotation inherits that status. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: Positive regulation of cell-cell adhesion, transferred from human MEGF10.

Reason: The human source annotation (IMP, PMID:31267131) is UNDECIDED in the human review because the cached abstract does not mention cell-cell adhesion. The transferred annotation inherits that status. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Summary: Muscle cell proliferation.

Reason: Electronic annotation. Megf10 knockdown, the EMARDD C774R mutation and Megf10 knockout all impair myoblast proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Muscle cell proliferation.

Reason: Transferred from human MEGF10. Megf10 knockdown, the EMARDD C774R mutation and Megf10 knockout all impair myoblast proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Homotypic cell-cell adhesion, transferred from the human annotation based on Kay et al. 2012.

Reason: Kay et al. 2012 was carried out in mouse retina. It shows Megf10-mediated homotypic recognition that produces intercellular repulsion (mosaic spacing), not adhesion, and no homophilic binding was detected. The same correction as in the human review applies. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Proposed replacements: cell-cell recognition

Summary: Homotypic cell-cell adhesion, transferred from the human annotation based on Kay et al. 2012.

Reason: Kay et al. 2012 was carried out in mouse retina. It shows Megf10-mediated homotypic recognition that produces intercellular repulsion (mosaic spacing), not adhesion, and no homophilic binding was detected. The same correction as in the human review applies. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Proposed replacements: cell-cell recognition

Summary: Homotypic cell-cell adhesion, transferred from the human annotation based on Kay et al. 2012.

Reason: Kay et al. 2012 was carried out in mouse retina. It shows Megf10-mediated homotypic recognition that produces intercellular repulsion (mosaic spacing), not adhesion, and no homophilic binding was detected. The same correction as in the human review applies. See genes/human/MEGF10/MEGF10-ai-review.yaml for the matching human decision.

Proposed replacements: cell-cell recognition

Summary: Engulfment of apoptotic cell (IBA, PTN002372116; sources ced-1, Draper and Megf10).

Reason: Megf10 is the mouse CED-1/Draper ortholog, an engulfment receptor that recognizes and phagocytoses apoptotic cells. This is its conserved core function.

Summary: Megf10-deficient astrocytes are impaired in phagocytosis of apoptotic cells (Iram et al. 2016).

Reason: IMP. Megf10 is the mouse CED-1/Draper ortholog, an engulfment receptor that recognizes and phagocytoses apoptotic cells. This is its conserved core function.

Summary: Megf10 expression lets fibroblasts bind dead neurons (Wu et al. 2009).

Reason: IDA. Recognition of apoptotic cells is the ligand-recognition step of the core function.

Summary: Knocking down Megf10 in glial precursors, or expressing a version without its intracellular domain, inhibits engulfment of apoptotic neurons.

Reason: IMP from Wu et al. 2009. It supports the recognition and engulfment role, though the phenotype reads out the whole engulfment process.

Summary: Cell development (ARBA).

Reason: Too general to be informative.

Summary: Myoblast development (IMP, Saha et al. 2019).

Reason: IMP from PMID:31267131. Megf10 is expressed in myoblasts but not differentiated myofibers and keeps myoblasts proliferating while inhibiting their differentiation, so it shapes myoblast progression. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. The cached record of PMID:31267131 is abstract-only and its abstract reports no result for this term, so the source paper is not quoted here; the term is supported by the other cited studies.

Summary: Regulation of skeletal muscle tissue development.

Reason: Electronic annotation. Loss of MEGF10 in EMARDD reduces satellite-cell-derived myofibers, and Megf10 balances satellite-cell proliferation against differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Regulation of skeletal muscle tissue development.

Reason: Transferred from human MEGF10. Loss of MEGF10 in EMARDD reduces satellite-cell-derived myofibers, and Megf10 balances satellite-cell proliferation against differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Regulation of muscle cell differentiation.

Reason: Electronic annotation. Megf10 overexpression inhibits myoblast differentiation and silencing causes precocious differentiation, a direct regulatory phenotype for muscle cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Regulation of muscle cell differentiation.

Reason: Transferred from human MEGF10. Megf10 overexpression inhibits myoblast differentiation and silencing causes precocious differentiation, a direct regulatory phenotype for muscle cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Regulation of muscle cell differentiation.

Reason: Transferred from mouse Megf10. Megf10 overexpression inhibits myoblast differentiation and silencing causes precocious differentiation, a direct regulatory phenotype for muscle cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Myoblast migration.

Reason: IBA. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Myoblast migration.

Reason: Electronic annotation. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Megf10-/- myoblasts show impaired migration (Saha et al. 2017).

Reason: IMP from PMID:28498977. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Myoblast migration.

Reason: Transferred from human MEGF10. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Muscle cell development.

Reason: Electronic annotation. MEGF10 regulates satellite-cell differentiation and fusion into multinucleated myofibers, which are reduced in EMARDD muscle. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Muscle cell development.

Reason: Transferred from human MEGF10. MEGF10 regulates satellite-cell differentiation and fusion into multinucleated myofibers, which are reduced in EMARDD muscle. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Muscle cell development.

Reason: Transferred from mouse Megf10. MEGF10 regulates satellite-cell differentiation and fusion into multinucleated myofibers, which are reduced in EMARDD muscle. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Apoptotic process involved in development (IMP, Iram et al. 2016).

Reason: The phenotype behind this IMP is more TUNEL- and cleaved-caspase-3-positive cells in the P7 cerebellum of Megf10-/- and Megf10+/- mice. The authors interpret this as a clearance defect, not a change in apoptosis. The Figure 1 title in the full text (PMC4863057, read for this review; not in the local cache) says that Megf10 "is necessary for apoptotic cell uptake by astrocytes, and its deficiency results in accumulation of apoptotic cells in the developing CB". Uncleared apoptotic cells accumulate whether or not more cells die. The same paper shows impaired astrocyte phagocytosis ex vivo and gain of phagocytosis on Megf10 expression. Megf10 acts in the engulfing cell and does none of the work of the apoptotic program. That role is captured by engulfment of apoptotic cell (GO:0043652, rows 31-32), which GO's own usage note separates from processes inside the dying cell. This is a recurring pattern in which a clearance-defect readout is annotated as the apoptotic process; see projects/APOPTOSIS/ASSAY_READOUT_OVERANNOTATION.md. The row's qualifier is acts_upstream_of_or_within, which a curator uses when a perturbation changes a process by an unknown route. That does not rescue it: the change measured is in clearance of dead cells, not in how many cells die, so Megf10 is neither upstream of nor within the apoptotic process.

Summary: Positive regulation of myoblast proliferation (ARBA).

Reason: Electronic annotation. Megf10 overexpression enhances myoblast proliferation and Megf10-deficient myoblasts proliferate poorly. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Positive regulation of myoblast proliferation (IMP, Saha et al. 2019).

Reason: IMP from PMID:31267131. Megf10 overexpression enhances myoblast proliferation and Megf10-deficient myoblasts proliferate poorly. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. The cached record of PMID:31267131 is abstract-only and its abstract reports no result for this term, so the source paper is not quoted here; the term is supported by the other cited studies.

Summary: Positive regulation of myoblast proliferation (ISO).

Reason: Transferred from human MEGF10. Megf10 overexpression enhances myoblast proliferation and Megf10-deficient myoblasts proliferate poorly. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core.

Summary: Astrocyte engulfment of synapses requires Megf10 (Chung et al. 2013).

Reason: Developing mice lacking the Megf10 and Mertk astrocyte pathways keep excess synapses. Megf10 is the engulfment receptor that does the recognition and uptake, so it does part of the work of synapse removal. Comparator: ITGAM and C1QA carry synapse-pruning terms. Synapse removal uses the same scavenger-receptor engulfment activity as apoptotic-cell clearance, acting on a different target, so it is listed under the core engulfment function.