abnormal wing discs (awd; also Killer of prune, Nm23) encodes the major nucleoside diphosphate kinase (NDPK, EC 2.7.4.6) of Drosophila, a 153-residue NME/Nm23-type enzyme about 78% identical to human NME1 and NME2. Purified Awd is a homohexamer that transfers the gamma-phosphate of ATP to ribo- and deoxyribonucleoside diphosphates by a ping-pong mechanism through an N-delta phosphohistidine on His119, with Mg2+ as cofactor; crystal structures of the free and phosphorylated enzyme have been solved. Awd is a soluble cytoplasmic protein that co-purifies with microtubules. Null mutants die around pupariation with small imaginal discs, lymph glands and brain lobes, and their neuroblasts arrest in metaphase. An H119A transgene that lacks NDPK activity does not rescue the null, so the catalytic activity is required in vivo; human NME2, but not NME1, can substitute. Genetic studies place Awd in dynamin (shibire)-dependent endocytosis: awd alleles enhance shibire synaptic-vesicle recycling defects, and loss of awd causes Breathless/FGFR to accumulate in tracheal cells, adherens-junction components to accumulate in follicle cells, and internalized Notch to stall in enlarged Rab5-positive early endosomes. In the ovary Awd negatively regulates border cell migration. Its down-regulation in border cells allows optimal spatial Pvr (PDGF/VEGF receptor) and JAK/STAT signalling, and its overexpression stalls migration and reverts the effects of constitutively active Pvr or dominant-negative dynamin. The favoured explanation is that Awd supplies GTP to dynamin and Rab5, but local GTP delivery has not been demonstrated directly.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000278 mitotic cell cycle | IMP PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | KEEP AS NON CORE | Summary: Neuroblasts of awd null larvae arrest in metaphase, which Biggs et al. attributed to a requirement for microtubule-associated Awd in spindle microtubule polymerization. Reason: The mutant phenotype is solid and was scored by the curator from the full paper, but it is a loss-of-function consequence: a cell-wide NTP-regenerating enzyme being necessary for mitosis does not show that Awd executes a step of the cell cycle. The likeliest link is GTP supply to tubulin polymerization, which has not been tested directly. Kept as a non-core, experimentally supported process; not suitable for transfer as a core function. Supporting Evidence: PMID:2175255 Neuroblasts in Drosophila larvae homozygous for a null mutation in the awd gene are arrested in metaphase, indicating that microtubule-associated Awd/NDP kinase plays a critical role in spindle microtubule polymerization. |
| GO:0000287 magnesium ion binding | IDA PMID:7669763 Mechanism of phosphate transfer by nucleoside diphosphate ki... | KEEP AS NON CORE | Summary: Mg2+ is the cofactor of NDPK catalysis; UniProt records Mg2+ as cofactor on the basis of the Drosophila phosphohistidine-intermediate crystal structures. Reason: Metal binding is part of the catalytic mechanism rather than an independent function. The cached record is abstract-only and the abstract does not mention Mg2+, but UniProt's curated cofactor statement cites this paper, so the curator's IDA is deferred to. Non-core because it is subsumed by the NDPK activity. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Evidence={ECO:0000269|PubMed:7669763}; PMID:7669763 Nucleoside diphosphate kinase (NDP kinase) has a ping-pong mechanism with a phosphohistidine intermediate. |
| GO:0004550 nucleoside diphosphate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places NDPK activity at PTN000887110, an ancestral node spanning bacterial, plant, fungal and animal NDPKs. Awd is inside this clade (PANTHER PTHR11349:SF91, with yeast YNK1 and worm ndk-1) and is itself one of the experimental donors (FB:FBgn0000150). Reason: The phylogenetic inference agrees with direct biochemistry on the fly enzyme: purified Awd has NDPK activity, forms the active-site phosphohistidine, and retains all catalytic and nucleotide-binding residues. Its own presence among the donors marks experimental grounding on the target. Supporting Evidence: PMID:2175255 We present evidence that the awd gene codes for a nucleoside diphosphate kinase (NDP kinase) and that this Awd/NDP kinase is microtubule associated. PMID:7669763 In both enzymes, the active site histidine was phosphorylated on N delta, and it was the only site of phosphorylation. |
| GO:0004550 nucleoside diphosphate kinase activity | IDA PMID:1320004 A Pro/Ser substitution in nucleoside diphosphate kinase of D... | ACCEPT | Summary: NDPK was purified from wild-type and Killer of prune larvae; both enzymes are hexamers with similar catalytic efficiency. Reason: Direct assay of the native fly enzyme. This is the core molecular function of Awd. Supporting Evidence: PMID:1320004 We purified the nucleoside diphosphate kinases from wild-type and mutant larvae by a simple procedure involving affinity chromatography on blue Sepharose. Both proteins are purified as hexamers in their native state. |
| GO:0004550 nucleoside diphosphate kinase activity | IDA PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | ACCEPT | Summary: Biggs et al. showed that the awd gene product is an NDP kinase. Reason: Original demonstration that Awd is an NDPK; core function. Supporting Evidence: PMID:2175255 We present evidence that the awd gene codes for a nucleoside diphosphate kinase (NDP kinase) and that this Awd/NDP kinase is microtubule associated. |
| GO:0004550 nucleoside diphosphate kinase activity | IDA PMID:8579610 A novel function for nucleoside diphosphate kinase in Drosop... | ACCEPT | Summary: Inoue et al. assayed the fly NDP kinase, which they describe as transferring the gamma-phosphate of NTPs to NDPs, and also reported autophosphorylation. Reason: Consistent with the other direct assays of fly NDPK; core function. Supporting Evidence: PMID:8579610 Nucleoside diphosphate (NDP) kinase is an enzyme that transfers the gamma-phosphate of nucleoside triphosphates to nucleoside diphosphates. |
| GO:0004550 nucleoside diphosphate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic mapping from the NDK family signature (IPR001564) and EC 2.7.4.6. Reason: Correct and confirmed by the experimental rows for this protein. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Belongs to the NDK family. {ECO:0000305}. |
| GO:0004550 nucleoside diphosphate kinase activity | IMP PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | ACCEPT | Summary: Loss of NDPK activity in awd mutants supports that awd encodes the larval enzyme. Reason: Consistent with the direct assays; core function. Supporting Evidence: PMID:2175255 We present evidence that the awd gene codes for a nucleoside diphosphate kinase (NDP kinase) |
| GO:0004550 nucleoside diphosphate kinase activity | IMP PMID:8579610 A novel function for nucleoside diphosphate kinase in Drosop... | ACCEPT | Summary: Kinase activity detected in wild-type extracts is absent from the awd mutant. Reason: Mutant-based support for the core enzymatic activity, in agreement with the H119A result that NDPK activity is required for awd function (PMID:8806830). Supporting Evidence: PMID:8579610 Protein kinase activity was not detected in NDP kinase mutant, abnormal wing discs (awd). PMID:8806830 a mutation that eliminates NDP kinase activity by replacement of the active site histidine with alanine |
| GO:0005524 ATP binding | IDA PMID:1320004 A Pro/Ser substitution in nucleoside diphosphate kinase of D... | KEEP AS NON CORE | Summary: ATP is the phosphate donor of NDPK, and the enzyme was purified on blue Sepharose, a nucleotide-site affinity resin. Reason: True, since ATP is the principal phosphoryl donor, but it is substrate binding that is part of the NDPK reaction rather than a separate function. UniProt lists ATP-binding residues (K13, Y61, R89, T95, R106, N116) by similarity to solved NDPK complexes. Supporting Evidence: PMID:1320004 affinity chromatography on blue Sepharose |
| GO:0005525 GTP binding | IDA PMID:8579610 A novel function for nucleoside diphosphate kinase in Drosop... | KEEP AS NON CORE | Summary: GTPgammaS served as phosphate donor in the protein-phosphorylation assay with fly NDPK. Reason: NDPKs bind all NTPs/NDPs at one site, so GTP binding is expected; it is substrate binding within the NDPK reaction. Non-core. Supporting Evidence: PMID:8579610 Ovalbumin was phosphorylated with guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) or ATP. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic NDPK activity placed at PTN000887110. Reason: Awd lacks any targeting sequence, is soluble, and UniProt records cytoplasmic location from Biggs et al. Consistent with the phylogenetic placement. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2175255}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Mapped from the curated UniProt subcellular location. Reason: The UniProt location rests on experimental evidence (PMID:2175255). Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2175255}. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial NDPK activity placed at PTN000142925, seeded by mitochondrial or mitochondria-associated NDPKs (human NME4 and NME3, yeast YNK1, Dictyostelium and plant mitochondrial isoforms). Reason: There is no Drosophila evidence for a mitochondrial pool of Awd. Awd has no N-terminal targeting extension, and the cited localization studies describe it as cytoplasmic and microtubule-associated. However, its PANTHER subfamily partner yeast YNK1 (PTHR11349:SF91), which also lacks a classical presequence, is one of the donors, and the PAINT curator placed the term on a node that contains Awd. No fly-specific evidence of loss argues against the node placement, so the row is kept as an inherited, non-core and unverified location. Do not transfer it as experimentally established for Awd. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2175255}. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from yeast YNK1 (P36010), which is in the same PANTHER subfamily (PTHR11349:SF91). Reason: The donor is a valid subfamily-level relative, and the claim matches the IBA row. Still, no experiment in Drosophila has detected Awd in mitochondria, and the bulk protein is cytoplasmic. Kept as non-core and unverified, in line with the IBA row. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Belongs to the NDK family. {ECO:0000305}. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MODIFY | Summary: Mapped from UniProt "Cytoplasm, cytoskeleton; Microtubule-associated". Reason: Correct but general. The underlying observation is association with microtubules, and the gene already carries the more specific GO:0005874 microtubule (IDA, PMID:2175255), which is part of the cytoskeleton. Proposed replacements: microtubule Supporting Evidence: PMID:2175255 this Awd/NDP kinase is microtubule associated |
| GO:0005874 microtubule | IDA PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | KEEP AS NON CORE | Summary: Awd/NDP kinase was shown to be microtubule-associated. Reason: Experimental, curator-read finding (abstract-only in cache). Microtubule association is a peripheral localization of a mainly cytosolic enzyme, so it is non-core. Supporting Evidence: PMID:2175255 this Awd/NDP kinase is microtubule associated |
| GO:0005880 nuclear microtubule | IMP PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | UNDECIDED | Summary: Location inferred from the metaphase-arrest phenotype of awd null neuroblasts, read as a requirement in spindle microtubule polymerization. Reason: A mutant phenotype cannot by itself show where a protein is located, and the cached record is abstract-only, so the localization evidence the curator used cannot be checked. The abstract supports association with microtubules generally (captured by GO:0005874) but does not state that Awd is on nuclear or spindle microtubules. Left undecided rather than overruling the curator. |
| GO:0005886 plasma membrane | HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi... | KEEP AS NON CORE | Summary: LOPIT organelle proteomics on Drosophila embryos assigned Awd to the plasma-membrane fraction. Reason: A single high-throughput fractionation call for a soluble protein. A peripheral pool near the plasma membrane is plausible given the genetic role in dynamin-dependent endocytosis and the reported presence of Awd at synapses (PMID:11343655), but it is not the main location. Supporting Evidence: PMID:19317464 Here, we apply LOPIT, a mass-spectrometry based technique that simultaneously maps proteins to specific subcellular compartments, to Drosophila embryos. PMID:11343655 NDK is present at synapses and its enzymatic activity is essential for normal presynaptic function. |
| GO:0006183 GTP biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping for the NDK family. Reason: NDPK catalyses the final step of GTP formation from GDP and ATP, so Awd performs the step. Null awd larvae retain only a low level of NDPK activity (PMID:11768313). Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Major role in the synthesis of nucleoside triphosphates other PMID:11343655 Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. |
| GO:0006183 GTP biosynthetic process | TAS PMID:7669763 Mechanism of phosphate transfer by nucleoside diphosphate ki... | ACCEPT | Summary: Traceable author statement from the structural study of the phosphotransfer mechanism. Reason: Same claim as the IEA row; Awd catalyses NDP to NTP phosphorylation. Supporting Evidence: PMID:7669763 Nucleoside diphosphate kinase (NDP kinase) has a ping-pong mechanism with a phosphohistidine intermediate. |
| GO:0006228 UTP biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping for the NDK family. Reason: NDPK is the general route from UDP to UTP. The fly enzyme acts on ribonucleoside diphosphates broadly (Rhea:18113, PMID:1320004). Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Major role in the synthesis of nucleoside triphosphates other |
| GO:0006228 UTP biosynthetic process | TAS PMID:7669763 Mechanism of phosphate transfer by nucleoside diphosphate ki... | ACCEPT | Summary: Traceable author statement, structural mechanism paper. Reason: Consistent with the broad NDP substrate range of NDPK. Supporting Evidence: PMID:7669763 Nucleoside diphosphate kinase (NDP kinase) has a ping-pong mechanism with a phosphohistidine intermediate. |
| GO:0006241 CTP biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping for the NDK family. Reason: NDPK converts CDP to CTP; consistent with the fly enzyme's broad NDP substrate range. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Major role in the synthesis of nucleoside triphosphates other |
| GO:0006241 CTP biosynthetic process | TAS PMID:7669763 Mechanism of phosphate transfer by nucleoside diphosphate ki... | ACCEPT | Summary: Traceable author statement, structural mechanism paper. Reason: Consistent with the broad NDP substrate range of NDPK. Supporting Evidence: PMID:7669763 Nucleoside diphosphate kinase (NDP kinase) has a ping-pong mechanism with a phosphohistidine intermediate. |
| GO:0007017 microtubule-based process | IMP PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | KEEP AS NON CORE | Summary: Based on the metaphase arrest of awd null neuroblasts, interpreted as defective spindle microtubule polymerization. Reason: Same mutant observation as the mitotic cell cycle row. The connection to microtubules is plausible (Awd co-purifies with microtubules and could supply GTP to tubulin) but has not been shown mechanistically. Non-core; do not transfer as a core function. Supporting Evidence: PMID:2175255 indicating that microtubule-associated Awd/NDP kinase plays a critical role in spindle microtubule polymerization |
| GO:0007424 open tracheal system development | IEP PMID:14630942 Drosophila awd, the homolog of human nm23, regulates FGF rec... | KEEP AS NON CORE | Summary: Awd protein is enriched in embryonic tracheal cells throughout tracheal development. Reason: Expression enrichment alone is weak support for a process, but the same paper also has the IMP evidence (mutant tracheal defects rescued by tracheal awd expression), so the two rows are kept consistently as a non-core developmental role. Awd's contribution is indirect, through endocytic downregulation of the FGF receptor Breathless. Supporting Evidence: PMID:14630942 Immunostaining of 1-eve-1 embryos with anti-Ξ²-Gal and anti-Awd antibodies showed that Awd is expressed at low levels in most of the embryonic cells and at high levels in the tracheal cells |
| GO:0007424 open tracheal system development | IMP PMID:14630942 Drosophila awd, the homolog of human nm23, regulates FGF rec... | KEEP AS NON CORE | Summary: Three independent awd alleles disrupt the embryonic tracheal network with ectopic branching and migration defects, and penetrance is rescued by tracheal awd expression. Reason: Well-supported genetic requirement. It reflects Awd's role in Breathless/FGFR turnover through shibire/dynamin-dependent endocytosis rather than a tracheal-specific activity, so it is non-core. Supporting Evidence: PMID:14630942 All three homozygous awd alleles show 75%β80% phenocopies. As shown in Supplementary Table 1, the penetrance can be rescued (down to 11%β15%) by a wild-type awd transgene expressed in the tracheal cells |
| GO:0007427 epithelial cell migration, open tracheal system | IMP PMID:14630942 Drosophila awd, the homolog of human nm23, regulates FGF rec... | KEEP AS NON CORE | Summary: Loss of awd causes dysregulated tracheal cell motility, suppressed by reducing breathless dosage. Reason: Awd restrains rather than drives migration, through FGFR levels. Non-core developmental context of its endocytic role. Supporting Evidence: PMID:14630942 We show that loss of Drosophila awd results in dysregulated tracheal cell motility. This phenotype can be suppressed by reducing the dosage of the chemotactic FGF receptor (FGFR) homolog, breathless (btl), indicating that btl and awd are functionally antagonists. |
| GO:0007427 epithelial cell migration, open tracheal system | IMP PMID:20516215 Drosophila von Hippel-Lindau tumor suppressor gene function ... | KEEP AS NON CORE | Summary: The dVHL tracheal study (abstract-only in cache) analysed branch migration controlled by Breathless surface levels; the curator annotated awd from the full text, presumably from genetic interaction experiments. Reason: The cached abstract does not mention awd, but the Hsu laboratory reports that dVHL interacts with Awd and that the two mutants share tracheal phenotypes. Consistent with the PMID:14630942 row, so the curator is deferred to as non-core. Supporting Evidence: PMID:19373545 For example, Drosophila awd and vhl mutants show similar tracheal phenotypes (49). |
| GO:0008017 microtubule binding | IDA PMID:2175255 A Drosophila gene that is homologous to a mammalian gene ass... | KEEP AS NON CORE | Summary: Awd/NDP kinase was found to be microtubule-associated. Reason: The abstract says only that Awd is "microtubule associated"; whether binding is direct cannot be judged from the cached text. The curator saw the full paper, so the annotation is kept, but as non-core, since no microtubule-dependent activity of Awd has been defined. Supporting Evidence: PMID:2175255 this Awd/NDP kinase is microtubule associated |
| GO:0009117 nucleotide metabolic process | TAS PMID:7669763 Mechanism of phosphate transfer by nucleoside diphosphate ki... | MODIFY | Summary: General nucleotide metabolism statement. Reason: Correct but general. The specific processes Awd catalyses are already annotated to this gene and are descendants of nucleotide metabolic process: GTP, UTP and CTP biosynthesis and deoxyribonucleoside triphosphate biosynthesis. Proposed replacements: GTP biosynthetic process UTP biosynthetic process CTP biosynthetic process deoxyribonucleoside triphosphate biosynthetic process Supporting Evidence: PMID:7669763 Nucleoside diphosphate kinase (NDP kinase) has a ping-pong mechanism with a phosphohistidine intermediate. |
| GO:0009142 nucleoside triphosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN000887110, same node as the NDPK activity IBA; Awd itself is a donor. Reason: The process directly catalysed by NDPK, at the level of specificity PAINT chose for the whole clade. Core process. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Major role in the synthesis of nucleoside triphosphates other PMID:1320004 Nucleoside diphosphate kinase of Drosophila, recently identified as the product of the awd gene, is essential for larval development. |
| GO:0009201 ribonucleoside triphosphate biosynthetic process | IDA PMID:1320004 A Pro/Ser substitution in nucleoside diphosphate kinase of D... | ACCEPT | Summary: The purified fly enzyme phosphorylates ribonucleoside diphosphates (UniProt cites Rhea:18113 to this paper). Reason: Directly assayed product formation by the native enzyme. Core. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Evidence={ECO:0000269|PubMed:1320004}; PMID:1320004 The mutant protein, which carries a serine instead of proline at position 97, has structural properties and catalytic efficiency that are very similar to the wild-type protein. |
| GO:0009202 deoxyribonucleoside triphosphate biosynthetic process | IDA PMID:1320004 A Pro/Ser substitution in nucleoside diphosphate kinase of D... | ACCEPT | Summary: The purified fly enzyme phosphorylates deoxyribonucleoside diphosphates (UniProt cites Rhea:44640 to this paper). Reason: Directly assayed. Null awd larvae retain only a low level of NDPK activity (Timmons and Shearn), so Awd is the main larval NDPK and a principal route from dNDPs to dNTPs. Core. Supporting Evidence: file:DROME/awd__P08879/awd__P08879-uniprot.txt Evidence={ECO:0000269|PubMed:1320004}; PMID:11768313 Null mutant larvae have a low level of nucleoside diphosphate kinase activity. |
| GO:0016301 kinase activity | IDA PMID:1320004 A Pro/Ser substitution in nucleoside diphosphate kinase of D... | MODIFY | Summary: Generic kinase activity from the NDPK assays of purified fly enzyme. Reason: Correct but general. The assayed activity is nucleoside diphosphate kinase activity (GO:0004550, an is_a descendant of kinase activity), which the gene already carries from the same paper. Proposed replacements: nucleoside diphosphate kinase activity Supporting Evidence: PMID:1320004 We purified the nucleoside diphosphate kinases from wild-type and mutant larvae |
| GO:0016334 establishment or maintenance of polarity of follicular epithelium | IMP PMID:19581292 The Drosophila metastasis suppressor gene Nm23 homolog, awd,... | KEEP AS NON CORE | Summary: awd mutant follicle-cell clones lose epithelial integrity (sheet breakage, piling up) and accumulate adherens-junction components. The epithelial function is mediated by Rab5. Reason: Solid clonal loss-of-function data from the full text. The polarity and integrity defects follow from impaired Rab5-dependent endocytic turnover of junction components, so this is a non-core developmental context. Supporting Evidence: PMID:19581292 Loss-of-function awd mutant cells result in the accumulation and spreading of adherens junction components, such as Drosophila E-cadherin, beta-catenin/Armadillo, and alpha-spectrin, and the disruption of epithelial integrity, including breaking up of the epithelial sheet and piling up of follicle cells. |
| GO:0034332 adherens junction organization | IMP PMID:19581292 The Drosophila metastasis suppressor gene Nm23 homolog, awd,... | KEEP AS NON CORE | Summary: Awd loss increases and spreads adherens-junction components; overexpression diminishes them. Reason: Bidirectional dosage effects make this a reasonable process annotation. The mechanism is endocytic turnover through Rab5, so it is non-core relative to the NDPK activity. Supporting Evidence: PMID:19581292 In contrast, overexpression of awd diminishes adherens junction components and induces a mesenchymal-cell-like cell shape change. PMID:19581292 Therefore, awd modulates the level and localization of adherens junction components via endocytosis. |
| GO:0035152 regulation of tube architecture, open tracheal system | IMP PMID:20516215 Drosophila von Hippel-Lindau tumor suppressor gene function ... | KEEP AS NON CORE | Summary: From the dVHL tracheal morphogenesis paper (abstract-only in cache); the curator annotated awd from the full-text genetic analysis. Reason: Cannot be verified from the cached abstract, but it is consistent with the established awd tracheal phenotypes (PMID:14630942) and the reported awd/vhl phenotypic similarity. Deferred to the curator as non-core. Supporting Evidence: PMID:19373545 For example, Drosophila awd and vhl mutants show similar tracheal phenotypes (49). |
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Download this section (compressed HTML)Q: Does Awd act in endocytosis by delivering GTP locally to dynamin (Shibire) and Rab5, or do the endocytic phenotypes reflect lower bulk GTP? Whether an annotation such as dynamin-dependent endocytosis is warranted depends on this. At present the evidence shows necessity, not participation, and the mammalian convention for NME1/NME2 should be checked first.
Q: Is any Awd present in mitochondria (for example the intermembrane space, like a fraction of yeast YNK1), as the PAINT mitochondrion node implies, or is the fly protein exclusively cytoplasmic and microtubule-associated?
Q: Is the histidine-dependent protein kinase activity reported for fly NDPK (PMID:8579610) physiologically relevant, given that it has not been reproduced for Awd?
Experiment: Rescue the awd null with H119A and with substrate-binding-site mutants targeted to endosomes or synapses, and measure local GTP/GDP with a genetically encoded sensor, to test whether NDPK-derived GTP is limiting for dynamin and Rab5 function.
Type: genetic rescue with biosensor imaging
Experiment: Fractionate adult and larval mitochondria (with protease protection) or use proximity labelling to test whether a pool of Awd resides in mitochondria.
Type: subcellular fractionation
abnormal wing discs (awd) encodes a nucleotide diphosphate kinase that regulates with the product of shi the endocytosis of different surface proteins (e.g. those encoded by N, btl, Pvr, and shg). During development, it regulates morphogenesis of trachea, follicular epithelium, and imaginal discs and contributes to neurotransmission and border cell migration.
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