drpr

UniProt ID: Q9W0A0
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Draper (drpr) is the Drosophila member of the CED-1/MEGF10 family of engulfment receptors, a single-pass type I transmembrane protein with an N-terminal EMI domain, a long array of atypical EGF-like repeats, and a cytoplasmic tail carrying an NPxY motif (binding the PTB adaptor Ced-6) and an immunoreceptor tyrosine-based activation motif (ITAM). Draper recognizes "eat-me" cues on dying cells and debris, including phosphatidylserine (directly or bridged by the secreted protein Orion), the apoptotic-cell surface protein Pretaporter, and bacterial lipoteichoic acid. Ligation promotes Src42A-dependent phosphorylation of the ITAM, recruitment of the Syk-family kinase Shark, Ced-6- and TRAF4-dependent signalling, Rac1-driven membrane extension and engulfment, and JNK/AP-1 and STAT92E transcriptional responses that further up-regulate draper expression. The activating isoform Draper-I is opposed by the alternatively spliced Draper-II, whose ITIM-like motif recruits the phosphatase Corkscrew to terminate glial responses. Draper mediates clearance by professional and non-professional phagocytes in many settings: engulfment of apoptotic cells by embryonic macrophages and glia, glial clearance of pruned and injury-severed axons, epidermal clearance of degenerating dendrites, glial and muscle removal of shed presynaptic debris at the neuromuscular junction, follicle cell engulfment of dying nurse cells, winner-cell engulfment during cell competition, and hemocyte phagocytosis of Staphylococcus aureus. It also acts as a damage receptor required for macrophage migration to wounds, its corpse-induced up-regulation primes macrophages for later inflammatory responses, and it is required cell-autonomously for autophagy during salivary gland cell death and for adult muscle maintenance.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001786 phosphatidylserine binding
IDA
PMID:23420848
Phosphatidylserine recognition and induction of apoptotic ce...
ACCEPT
Summary: Solid-phase and surface plasmon resonance assays show the Draper extracellular region binds phosphatidylserine directly; the EMI/NIM N-terminal region is required.
Reason: Direct biochemical evidence that Draper recognizes the PS eat-me signal; this ligand-binding activity is a core part of its receptor function, supported independently by PS-bead reconstitution (PMID:30139739).
Supporting Evidence:
PMID:23420848
We found that the extracellular region of Draper, an engulfment receptor of Drosophila, binds to phosphatidylserine in an enzyme-linked immunosorbent assay-like solid-phase assay and in an assay for surface plasmon resonance.
PMID:30139739
PS-ligated Draper forms dynamic microclusters that recruit cytosolic effector proteins
GO:0001891 phagocytic cup
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt SubCell mapping (Cell projection, phagocytic cup), based on follicle cell imaging.
Reason: Draper is present on the phagocytic cup of engulfing follicle cells, the site where it acts as an engulfment receptor; consistent with CED-1 enrichment around corpses.
Supporting Evidence:
PMID:27347682
The phagocytic receptor Draper is present on the phagocytic cup and on nascent, phosphatidylinositol 3-phosphate (PI(3)P)- and Rab7-positive phagosomes
GO:0005044 scavenger receptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA from the CED-1/Draper/MEGF10 node (PTN009076277), with drpr's own family members CED-1 and MEGF10 among the seeds.
Reason: Draper is the fly member of the CED-1/MEGF10 scavenger-receptor-like engulfment receptor clade and binds modified-self and polyanionic ligands (phosphatidylserine, Pretaporter, lipoteichoic acid). The IBD node placement is consistent with the conserved function; this is the best available MF term for the recognition function.
Supporting Evidence:
PMID:23420848
Draper is a phosphatidylserine-binding receptor for phagocytosis
PMID:19890048
lipoteichoic acid bound to the extracellular region of Draper
PMID:18432193
Draper seems to be an ancient immunoreceptor with an extracellular domain tuned to modified self
GO:0005044 scavenger receptor activity
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO from IPR042635 (MEGF10/SREC1/2-like).
Reason: Family membership mapping agrees with the IBA and with direct ligand-binding evidence for Draper (PS, LTA, Pretaporter).
Supporting Evidence:
file:DROME/drpr/drpr-uniprot.txt
InterPro; IPR042635; MEGF10/SREC1/2-like.
PMID:19927123
An endoplasmic reticulum protein that binds to the extracellular region of Draper was isolated.
GO:0005515 protein binding
IPI
PMID:16772168
Essential role of the apoptotic cell engulfment genes draper...
MODIFY
Summary: IPI with Ced-6 (Q7JUY7), the PTB-domain adaptor that binds the Draper NPxY motif.
Reason: Bare protein binding is uninformative. The Ced-6 interaction reflects recruitment of a cytoplasmic adaptor to the receptor tail; the NPxY motif is essential for Draper-mediated phagocytosis. The informative MF is the receptor's signaling activity.
Supporting Evidence:
PMID:16772168
drpr and ced-6 interact genetically in the glial action
PMID:23337816
This coincides with our previous finding that Ced-6, an NPxY-binding signaling adaptor, is required for Draper's actions in apoptotic cell clearance.
GO:0005515 protein binding
IPI
PMID:18432193
Draper-dependent glial phagocytic activity is mediated by Sr...
MODIFY
Summary: IPI with Shark (Q24145), the Syk-family kinase that binds the phosphorylated Draper ITAM.
Reason: Bare protein binding is uninformative. Shark is recruited to the Src42A-phosphorylated ITAM in the Draper tail, the signal-transducing step of an immunoreceptor-like transmembrane receptor.
Supporting Evidence:
PMID:18432193
We propose that ligand-dependent Draper receptor activation initiates the Src42A-dependent tyrosine phosphorylation of Draper, the association of Shark and the activation of the Draper pathway.
GO:0005515 protein binding
IPI
PMID:19927123
Pretaporter, a Drosophila protein serving as a ligand for Dr...
MODIFY
Summary: IPI with Pretaporter (Q9VYV3), an ER protein exposed on apoptotic cells that binds the Draper extracellular region.
Reason: Bare protein binding is uninformative. Pretaporter is a ligand; its binding augments Draper tyrosine phosphorylation, i.e. ligand-triggered transmembrane receptor signaling.
Supporting Evidence:
PMID:19927123
Finally, the incubation with Pretaporter augmented the tyrosine-phosphorylation of Draper in phagocytic cells.
GO:0005737 cytoplasm
IDA
PMID:22992958
Draper acts through the JNK pathway to control synchronous e...
KEEP AS NON CORE
Summary: In engulfing follicle cells Drpr is detected in cytoplasmic puncta in addition to the plasma membrane.
Reason: The puncta are interpreted as internalized receptor during phagosome formation; the cytoplasmic signal is real but secondary to the plasma membrane/phagocytic cup site of action. The assay cannot resolve the vesicle compartment, so the term is not modified.
Supporting Evidence:
PMID:22992958
In addition to plasma membrane staining, Drpr was detected in punctate speckles within FC cytoplasm.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt SubCell mapping (Cytoplasm), derived from follicle cell and macrophage imaging.
Reason: Consistent with the IDA row; cytoplasmic puncta likely represent internalized receptor on phagosomes. Non-core relative to the plasma membrane.
Supporting Evidence:
PMID:27212238
this is accompanied by relocalization of Draper protein from cytosolic punctae to the cell cortex
GO:0005886 plasma membrane
EXP
PMID:18455990
Six-microns-under acts upstream of Draper in the glial phago...
ACCEPT
Summary: Draper protein shows uniform plasma membrane distribution on embryonic macrophages and glia.
Reason: Single-pass type I transmembrane receptor detected on the cell surface; core location.
Supporting Evidence:
PMID:18455990
Interestingly, the DRPR protein distribution on the plasma membrane is fairly uniform, while SIMU's appears more patchy
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA (is_active_in plasma membrane) with drpr, CED-1, MEGF10 and others as seeds.
Reason: Consistent with direct evidence and with the conserved surface receptor role of the clade.
Supporting Evidence:
PMID:18455990
double labeling of simu-SIMU-MYC and DRPR antibodies reveals strongly overlapping expression of the two proteins on the cell surface of macrophages and glia
GO:0005886 plasma membrane
IDA
PMID:12765609
Unwrapping glial biology: Gcm target genes regulating glial ...
ACCEPT
Summary: Plasma membrane localization from the Gcm target gene study (abstract only cached).
Reason: Defer to curator; plasma membrane localization is well established by several independent studies.
Supporting Evidence:
file:DROME/drpr/drpr-uniprot.txt
Cell membrane {ECO:0000269|PubMed:12765609
GO:0005886 plasma membrane
IDA
PMID:22992958
Draper acts through the JNK pathway to control synchronous e...
ACCEPT
Summary: Drpr enriched on the apical membrane of engulfing follicle cells bordering the germline.
Reason: Direct imaging in follicle cells; core location.
Supporting Evidence:
PMID:22992958
Drpr became enriched on the apical membrane of engulfing FCs, bordering the germline
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated annotation (UniProt SubCell Cell membrane; ARBA).
Reason: Correct and consistent with experimental evidence.
Supporting Evidence:
PMID:18455990
Interestingly, the DRPR protein distribution on the plasma membrane is fairly uniform
GO:0005938 cell cortex
IEA
GO_REF:0000044
MARK AS OVER ANNOTATED
Summary: UniProt SubCell mapping (Cytoplasm, cell cortex) from the macrophage priming study, where Draper relocalizes from punctae to the cell cortex at stage 15.
Reason: Draper is a single-pass transmembrane receptor; peripheral ("cortical") staining by light microscopy indicates the plasma membrane, not the cytoplasmic cell cortex compartment beneath it. The plasma membrane is already accepted.
Supporting Evidence:
PMID:27212238
this is accompanied by relocalization of Draper protein from cytosolic punctae to the cell cortex
file:DROME/drpr/drpr-uniprot.txt
Single-pass type I membrane protein
GO:0006909 phagocytosis
IMP
PMID:15342648
Draper-mediated and phosphatidylserine-independent phagocyto...
MODIFY
Summary: RNAi of Draper in hemocyte-derived l(2)mbn cells and embryos reduces phagocytosis of apoptotic cells.
Reason: Correct but general; the evidence specifically concerns engulfment of apoptotic cells, a term already carried by drpr (IBA, IMP).
Proposed replacements: engulfment of apoptotic cell
Supporting Evidence:
PMID:15342648
apoptotic cell phagocytosis was reduced when the expression of Draper, but not of Croquemort, was inhibited by RNA interference in hormone-treated l(2)mbn cells
GO:0006909 phagocytosis
IMP
PMID:19890048
Identification of lipoteichoic acid as a ligand for draper i...
MODIFY
Summary: Draper is required for ltaS-dependent phagocytosis of S. aureus by hemocytes.
Reason: Correct but general; the evidence is for engulfment of bacteria by hemocytes. Phagocytosis, engulfment is the specific supported descendant already carried by drpr.
Proposed replacements: phagocytosis, engulfment
Supporting Evidence:
PMID:19890048
ltaS-dependent phagocytosis of S. aureus required the receptor Draper but not Eater or Nimrod C1
GO:0006909 phagocytosis
IMP
PMID:37248218
LC3-associated phagocytosis promotes glial degradation of ax...
MODIFY
Summary: Glial LC3-associated phagocytosis study; drpr heterozygosity used as a sensitized background for axon debris phagocytosis.
Reason: Correct but general; Draper is the receptor mediating glial engulfment of axon debris. The specific supported term is phagocytosis, engulfment.
Proposed replacements: phagocytosis, engulfment
Supporting Evidence:
PMID:37248218
In drpr homozygous null mutant flies, glial cells fail to even contact axon debris
GO:0006909 phagocytosis
TAS
PMID:14602069
Thicker than blood: conserved mechanisms in Drosophila and v...
MODIFY
Summary: TAS from a review of Drosophila hematopoiesis (abstract only cached).
Reason: Phagocytosis is correct but general; Draper's experimentally supported phagocytic roles are engulfment of apoptotic cells and engulfment of other targets (axon debris, bacteria), both already carried by drpr.
Supporting Evidence:
PMID:15342648
These results indicate that Drosophila hemocytes/macrophages execute Draper-mediated phagocytosis to eliminate apoptotic cells.
GO:0006911 phagocytosis, engulfment
IMP
PMID:22426252
Negative regulation of glial engulfment activity by Draper t...
ACCEPT
Summary: Draper-I promotes glial engulfment of axonal debris via its ITAM; Draper-II inhibits it.
Reason: Core process; Draper is the engulfment receptor for axonal debris in glia.
Supporting Evidence:
PMID:22426252
Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM).
GO:0006911 phagocytosis, engulfment
IMP
PMID:24361692
Astrocytes engage unique molecular programs to engulf pruned...
ACCEPT
Summary: Astrocytes use Draper to engulf pruned vCrz+ neuronal cell bodies.
Reason: Draper acts directly as the engulfment receptor in astrocytes for neuronal debris.
Supporting Evidence:
PMID:24361692
are engulfed by astrocytes using the Draper and Crk/Mbc/dCed-12 signaling
GO:0008345 larval locomotory behavior
IMP
PMID:12765609
Unwrapping glial biology: Gcm target genes regulating glial ...
KEEP AS NON CORE
Summary: draper mutants show larval locomotion defects.
Reason: Locomotor phenotype is real but downstream of engulfment and muscle maintenance roles; non-core behavioral consequence.
Supporting Evidence:
PMID:12765609
the draper gene mediates glial engulfment of apoptotic neurons and larval locomotion
PMID:25111228
Tissue-specific RNAi experiments demonstrated that drpr deficiency in muscle, but not in the brain, leads to locomotor defects.
GO:0009611 response to wounding
IGI
PMID:33296680
PTPN21/Pez Is a Novel and Evolutionarily Conserved Key Regul...
KEEP AS NON CORE
Summary: Genetic interaction of drpr with Pez (PTPN21) in macrophage recruitment to epithelial wounds.
Reason: Draper acts as a damage receptor in macrophages (H2O2-Src42A-Draper-Shark) driving inflammatory migration to wounds; a genuine but secondary role compared with engulfment.
Supporting Evidence:
PMID:33296680
Pez Is Required for Macrophage Migration to Epithelial Wounds and Functions within the H2O2-Src42A-Draper Signaling Pathway
PMID:26028435
The Src42A-Draper-Shark-mediated signaling axis is homologous to the well-established SFK-ITAM-Syk-signaling pathway
GO:0016020 membrane
NAS
PMID:15342648
Draper-mediated and phosphatidylserine-independent phagocyto...
MODIFY
Summary: NAS membrane localization.
Reason: Correct but general; Draper is a single-pass plasma membrane receptor (plasma membrane already accepted from direct evidence).
Proposed replacements: plasma membrane
Supporting Evidence:
PMID:18455990
Interestingly, the DRPR protein distribution on the plasma membrane is fairly uniform
GO:0016192 vesicle-mediated transport
IEA
GO_REF:0000108
TOO GENERAL
Summary: Inter-ontology inference from scavenger receptor activity.
Reason: True (phagocytosis is a form of vesicle-mediated transport) but uninformative beside the accepted phagocytosis, engulfment and engulfment of apoptotic cell terms, which entail it.
Supporting Evidence:
PMID:22426252
Draper-I promotes engulfment of axonal debris
GO:0016322 neuron remodeling
IMP
PMID:16772168
Essential role of the apoptotic cell engulfment genes draper...
KEEP AS NON CORE
Summary: drpr mutation and glial knockdown suppress glial engulfment of larval mushroom body axons and inhibit axon pruning during metamorphosis.
Reason: Draper participates in neuron remodeling by performing the glial engulfment step of axon pruning; this is a developmental context of its core engulfment function.
Supporting Evidence:
PMID:16772168
The drpr mutation and glia-specific knockdown of drpr and ced-6 by RNA interference suppress glial engulfment, resulting in the inhibition of axon pruning.
GO:0016322 neuron remodeling
IMP
PMID:16772170
Wlds protection distinguishes axon degeneration following in...
KEEP AS NON CORE
Summary: Draper is required for efficient clearance of axon fragments during developmental axon pruning.
Reason: Same claim as the other neuron remodeling row; developmental context of the glial engulfment function.
Supporting Evidence:
PMID:16772170
the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration
GO:0030054 cell junction
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA machine-learning prediction of cell junction.
Reason: Draper is found at the NMJ postsynaptic membrane (synapse is a cell junction in GO), so the claim is true but uninformative beside the postsynaptic membrane term kept in this review.
Supporting Evidence:
PMID:19707574
Draper is present postsynaptically at the NMJ surrounding HRP+ presynaptic boutons
IEA
GO_REF:0000044
UNDECIDED
Summary: UniProt SubCell mapping (Cell projection, axon) derived from PMID:16772169.
Reason: The cached abstract of PMID:16772169 describes Draper as a glial receptor up-regulated in glia that extend processes to severed axons; staining around axons may be glial. UniProt states low-level expression along ORN axons, but the full text could not be checked to confirm a neuronal pool.
Supporting Evidence:
PMID:16772169
Thus Draper appears to act as a glial receptor for severed axon-derived molecular cues that drive recruitment of glial processes to injured axons for engulfment.
IMP
PMID:16772169
The Drosophila cell corpse engulfment receptor Draper mediat...
UNDECIDED
Summary: UniProt-assigned axon location (IMP) from the glial clearance of severed axons study.
Reason: As for the IEA row; the abstract only supports glial Draper. Neuronal axonal Draper cannot be verified without the full text.
Supporting Evidence:
PMID:16772169
glia upregulate expression of the engulfment receptor Draper, undergo dramatic changes in morphology, and rapidly recruit cellular processes toward severed axons
GO:0035212 cell competition in a multicellular organism
IMP
PMID:17574031
Engulfment is required for cell competition.
KEEP AS NON CORE
Summary: draper is required in wild-type cells to kill and engulf Minute neighbours.
Reason: Real but context-specific role, mediated through engulfment of loser cells.
Supporting Evidence:
PMID:17574031
The engulfment genes draper, wasp, the phosphatidylserine receptor, mbc/dock180, and rac1 are needed in wild-type cells for the death of Minute neighbors
GO:0042742 defense response to bacterium
IMP
PMID:19890048
Identification of lipoteichoic acid as a ligand for draper i...
KEEP AS NON CORE
Summary: Draper-lacking flies show reduced resistance to septic S. aureus infection without humoral defects.
Reason: Draper contributes to defense by hemocyte phagocytosis of bacteria; secondary to its corpse/debris clearance role.
Supporting Evidence:
PMID:19890048
Draper-lacking flies showed reduced resistance to a septic infection of S. aureus without a change in a humoral immune response
GO:0043277 apoptotic cell clearance
IMP
PMID:18432193
Draper-dependent glial phagocytic activity is mediated by Sr...
ACCEPT
Summary: Shark/Src42A signalling downstream of Draper is required for glial phagocytosis of neuronal corpses and axon debris.
Reason: Core process; Draper is the glial receptor for apoptotic neuron clearance.
Supporting Evidence:
PMID:18432193
Shark activity is essential for Draper-mediated signalling events in vivo, including the recruitment of glial membranes to severed axons and the phagocytosis of axonal debris and neuronal cell corpses by glia
GO:0043277 apoptotic cell clearance
IMP
PMID:18455990
Six-microns-under acts upstream of Draper in the glial phago...
ACCEPT
Summary: drpr mutant embryos accumulate apoptotic particles inside glial phagocytes; drpr is primarily required for corpse degradation downstream of SIMU.
Reason: Apoptotic cell clearance (encompassing engulfment and degradation) is the right level here because in embryonic glia drpr loss mainly impairs corpse degradation rather than uptake.
Supporting Evidence:
PMID:18455990
These findings indicate that drpr and simu have distinct functions, with simu involved in recognition and uptake, and drpr primarily required for the degradation of cell corpses.
GO:0043277 apoptotic cell clearance
IMP
PMID:19369546
Ensheathing glia function as phagocytes in the adult Drosoph...
ACCEPT
Summary: Ensheathing glia express Draper and autonomously require the Draper pathway as phagocytes in the adult brain.
Reason: The cited paper focuses on axon debris rather than apoptotic cells, but the clearance claim for Draper is well established and the FlyBase curator read the full text; defer.
Supporting Evidence:
PMID:19369546
we find these glia uniquely express key components of the glial phagocytic machinery (e.g., the engulfment receptor Draper, and dCed-6), respond morphologically to axon injury, and autonomously require components of the Draper signaling pathway
GO:0043652 engulfment of apoptotic cell
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA from node PTN002372116 seeded by drpr, CED-1 and MEGF10.
Reason: Engulfment of apoptotic cells is the ancestral function of the CED-1/Draper/MEGF10 clade and is directly shown for Draper in hemocytes, glia and follicle cells.
Supporting Evidence:
PMID:15342648
These results indicate that Drosophila hemocytes/macrophages execute Draper-mediated phagocytosis to eliminate apoptotic cells.
GO:0043652 engulfment of apoptotic cell
IMP
PMID:22992958
Draper acts through the JNK pathway to control synchronous e...
ACCEPT
Summary: Draper is required in follicle cells for engulfment of dying germline cells and acts through JNK.
Reason: Direct evidence for a core function in a non-professional phagocyte.
Supporting Evidence:
PMID:22992958
We find that the receptor Draper is also required in engulfing follicle cells, and activates the JNK pathway.
GO:0045211 postsynaptic membrane
EXP
PMID:19707574
Glia and muscle sculpt neuromuscular arbors by engulfing des...
KEEP AS NON CORE
Summary: Draper immunoreactivity surrounds every NMJ bouton and colocalizes with the postsynaptic marker DLG; contributed in part by muscle.
Reason: Real location where muscle Draper engulfs ghost boutons and debris, but a tissue-specific site rather than the general receptor location.
Supporting Evidence:
PMID:19707574
Draper is present postsynaptically at the NMJ surrounding HRP+ presynaptic boutons (Cii), and colocalizes with the primarily postsynaptic marker DLG (Ciii)
GO:0045211 postsynaptic membrane
EXP
PMID:22992958
Draper acts through the JNK pathway to control synchronous e...
KEEP AS NON CORE
Summary: UniProt EXP for postsynaptic membrane citing the follicle cell engulfment paper.
Reason: The claim itself is supported by PMID:19707574, so it is kept (consistent with the other rows), but PMID:22992958 studies ovarian follicle cells and its full text contains no synapse or NMJ data; the reference appears mis-attached in UniProt's merged SubCell evidence.
Supporting Evidence:
PMID:19707574
Draper is expressed in peripheral glia and in the postsynaptic region of the NMJ.
GO:0045211 postsynaptic membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt SubCell mapping (Postsynaptic cell membrane).
Reason: Supported by NMJ immunostaining (PMID:19707574); tissue-specific, non-core location.
Supporting Evidence:
PMID:19707574
Draper is present at every NMJ and surrounding each synaptic bouton
GO:0045335 phagocytic vesicle
IEA
GO_REF:0000044
MODIFY
Summary: UniProt SubCell mapping (Cytoplasmic vesicle, phagosome) from follicle cell imaging.
Reason: Correct but general for a transmembrane receptor; Draper sits on the membrane of nascent phagosomes, so phagocytic vesicle membrane is the specific supported term.
Proposed replacements: phagocytic vesicle membrane
Supporting Evidence:
PMID:27347682
The phagocytic receptor Draper is present on the phagocytic cup and on nascent, phosphatidylinositol 3-phosphate (PI(3)P)- and Rab7-positive phagosomes
GO:0048102 autophagic cell death
IMP
PMID:20577216
Activation of autophagy during cell death requires the engul...
KEEP AS NON CORE
Summary: drpr is required cell-autonomously in dying salivary gland cells for induction of autophagy and gland degradation.
Reason: A striking, well-supported, but tissue-specific role distinct from engulfment by a neighbouring phagocyte; non-core.
Supporting Evidence:
PMID:20577216
Null mutations in, and salivary gland-specific knockdown of, drpr inhibit salivary gland degradation. Knockdown of drpr prevents the induction of autophagy in dying salivary glands
GO:0048190 wing disc dorsal/ventral pattern formation
IGI
PMID:18202376
A gain-of-function suppressor screen for genes involved in d...
MARK AS OVER ANNOTATED
Summary: Loss-of-function draper EP insertion suppressed the Beadex1 wing phenotype in a gain-of-function suppressor screen.
Reason: Genetic modifier interaction only; the same paper states draper is not essential for wing development, so a role in wing D/V pattern formation is not established.
Supporting Evidence:
PMID:18202376
We have shown that many of the Bx 1 suppressors involved in DV boundary formation are not essential during wing development ( i.e ., taranis , nmd , nuf , draper , and cabut
GO:0048468 cell development
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA machine-learning prediction (cell development).
Reason: Vague ARBA prediction not supported by a specific developmental role of Draper in cell differentiation; drpr's developmental effects (pruning, NMJ growth, muscle maintenance) are consequences of engulfment and are captured by more specific terms.
Supporting Evidence:
PMID:16772170
the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration
GO:0048513 animal organ development
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA machine-learning prediction (animal organ development).
Reason: Generic ARBA prediction; muscle degeneration in drpr knockdown reflects tissue maintenance rather than organ development, and other developmental effects are engulfment-dependent.
Supporting Evidence:
PMID:25111228
Our analysis of drpr mutant flies revealed muscle degeneration with fiber size variability and vacuolization, as well as reduced motor performance
GO:0048678 response to axon injury
IMP
PMID:16772169
The Drosophila cell corpse engulfment receptor Draper mediat...
ACCEPT
Summary: In draper mutants glia fail to respond morphologically to axon injury and severed axons are not cleared.
Reason: Draper is the glial receptor that drives the injury response (process recruitment, JNK/STAT92E transcription, engulfment); a core, well-replicated function.
Supporting Evidence:
PMID:16772169
In draper mutants, glia fail to respond morphologically to axon injury, and severed axons are not cleared from the CNS.
PMID:28165006
Draper is cell autonomously required for glial activation of transcriptional reporters after axonal injury
GO:0048678 response to axon injury
IMP
PMID:24958874
Rapid in vivo forward genetic approach for identifying axon ...
ACCEPT
Summary: Wing L1 vein axotomy method paper (abstract does not name draper); curator presumably used drpr data in the full text.
Reason: Full text not cached; the claim is well supported for Draper (PMID:16772169) and in the wing nerve (PMID:37248218), so defer to the FlyBase curator.
Supporting Evidence:
PMID:37248218
only Draper's essential role for debris engulfment by wrapping (and to a lesser extent by subperineurial) glia has been established in the PNS
GO:0060100 positive regulation of phagocytosis, engulfment
IMP
PMID:24412417
Epidermal cells are the primary phagocytes in the fragmentat...
MODIFY
Summary: drpr is required in epidermal cells for engulfment of degenerating dendrite debris.
Reason: Draper is the engulfment receptor itself, so it is directly involved in phagocytosis, engulfment rather than regulating it.
Proposed replacements: phagocytosis, engulfment
Supporting Evidence:
PMID:24412417
drpr is required for engulfment of dendrite debris by epidermal cells
GO:0098794 postsynapse
IMP
PMID:19707574
Glia and muscle sculpt neuromuscular arbors by engulfing des...
MODIFY
Summary: Draper localizes to the NMJ postsynaptic region.
Reason: Correct but general; the evidence (DLG colocalization) supports postsynaptic membrane, which is already annotated.
Proposed replacements: postsynaptic membrane
Supporting Evidence:
PMID:19707574
Draper is present postsynaptically at the NMJ surrounding HRP+ presynaptic boutons (Cii), and colocalizes with the primarily postsynaptic marker DLG (Ciii)
GO:1904396 regulation of neuromuscular junction development
IMP
PMID:19707574
Glia and muscle sculpt neuromuscular arbors by engulfing des...
KEEP AS NON CORE
Summary: draper mutant NMJs show reduced synaptic growth and accumulate ghost boutons and presynaptic debris.
Reason: The NMJ growth effect is a consequence of failed debris clearance by glia and muscle; a valid but non-core developmental role.
Supporting Evidence:
PMID:19707574
draper mutant NMJs exhibit reduced synaptic growth and accumulate pruned ghost boutons and presynaptic debris.
GO:0043654 recognition of apoptotic cell
IDA
PMID:23420848
Phosphatidylserine recognition and induction of apoptotic ce...
NEW
Summary: Draper directly binds the apoptotic-cell eat-me signal phosphatidylserine and the apoptotic-cell surface ligand Pretaporter, and these ligands trigger Draper tyrosine phosphorylation.
Reason: Draper is the receptor that performs the recognition step: its extracellular EMI/NIM region binds PS and its EGF-like repeats bind Pretaporter, and ligand engagement activates it. This is participation, not mere requirement, and parallels the curated recognition annotation for its ortholog CED-1. Not entailed by any existing drpr row.
Supporting Evidence:
PMID:23420848
A portion of Draper containing domains EMI and NIM located close to the N-terminus was required for binding to phosphatidylserine
PMID:19927123
cells artificially expressing Pretaporter at their surface became susceptible to Draper-mediated phagocytosis
PMID:23337816
Draper binds to its ligand Pretaporter using EGF-like sequences

Core Functions

Cell-surface engulfment receptor that recognizes eat-me signals (phosphatidylserine, Pretaporter, lipoteichoic acid) on apoptotic cells, neuronal debris and bacteria, and drives their engulfment by macrophages, glia, epidermal and follicle cells.

Supporting Evidence:
  • PMID:23420848
    Draper is a phosphatidylserine-binding receptor for phagocytosis
  • PMID:19927123
    Pretaporter relocates from the endoplasmic reticulum to the cell surface during apoptosis to serve as a ligand for Draper in the phagocytosis of apoptotic cells
  • PMID:15342648
    These results indicate that Drosophila hemocytes/macrophages execute Draper-mediated phagocytosis to eliminate apoptotic cells.
  • PMID:27347682
    The phagocytic receptor Draper is present on the phagocytic cup

ITAM/NPxY-bearing transmembrane signalling receptor that, after ligation, is phosphorylated by Src42A and recruits Shark, Ced-6 and TRAF4 to activate engulfment and JNK/STAT92E-dependent glial responses to axon injury; isoform Draper-II antagonizes this signalling via Corkscrew.

Supporting Evidence:
  • PMID:18432193
    We propose that ligand-dependent Draper receptor activation initiates the Src42A-dependent tyrosine phosphorylation of Draper, the association of Shark and the activation of the Draper pathway.
  • PMID:28165006
    Draper is cell autonomously required for glial activation of transcriptional reporters after axonal injury
  • PMID:22426252
    Draper-II suppresses Draper-I signaling through a previously undescribed immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew (Csw).
  • PMID:16772169
    In draper mutants, glia fail to respond morphologically to axon injury, and severed axons are not cleared from the CNS.

References

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Suggested Questions for Experts

Q: Is the 'scavenger receptor activity' term the right MF for CED-1/Draper/MEGF10-family receptors, whose ligands include phosphatidylserine and proteins rather than modified lipoproteins, or is a more specific 'apoptotic cell receptor activity'-type term needed?

Q: Does Draper signal as a damage receptor in macrophages (H2O2-Src42A-Draper-Shark) through a ligand, or is it activated ligand-independently by oxidant-triggered Src42A?

Q: How does Draper act cell-autonomously in dying salivary gland cells to induce autophagy, and what ligand engages it in that self-clearance context?

Q: Is Draper present in neuronal axons (as UniProt states for olfactory receptor neurons), or does all axonal-region staining after injury derive from glial processes?

Q: Should UniProt's evidence for 'Postsynaptic cell membrane' on Q9W0A0 cite PMID:19707574 only, rather than PMID:22992958 (a follicle cell study)?

Suggested Experiments

Experiment: Compare Draper immunostaining around severed ORN axons after glia-specific versus neuron-specific drpr RNAi, or with an endogenously tagged drpr allele imaged with cell-type-specific membrane markers.

Hypothesis: Draper is not expressed in olfactory receptor neurons and the axonal signal after injury is glial.

Type: imaging

Experiment: Express Draper-I alone or Draper-I plus Draper-II in H99 macrophages and score wound recruitment and bacterial uptake after corpse-independent Draper induction.

Hypothesis: The Draper-II ITIM-like motif is required to terminate macrophage priming as it is for glial responses.

Type: genetic

Deep Research

FlyBase

(drpr-deep-research-flybase.md)
FlyBase gene description for drpr (DROME) FlyBase

FlyBase gene description for drpr (DROME)

draper (drpr) encodes a single-pass transmembrane receptor that is involved in phagocytosis by glia, macrophages, and epithelia. It signals downstream through the proteins encoded by Src42A and Shark to promote Rac1 function and transcriptional changes through the products of Jra and Stat92E. It is also required for activation of autophagy in salivary glands.

πŸ“š Additional Documentation

Notes

(drpr-notes.md)

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