Discs large (Dlg) is the Drosophila membrane-associated guanylate kinase homolog (MAGUK), the founding member of the PSD-95/SAP97 family. Its L27 (DlgS97 isoforms), three PDZ, SH3 and guanylate kinase-like (GUK) domains form a peripheral membrane scaffold. The GUK domain is a non-catalytic protein-interaction module. In epithelia Dlg sits on the cytoplasmic face of the septate junction and lateral membrane. With Scribble and Lethal giant larvae it defines the basolateral domain, maintaining apicobasal polarity, septate junctions and proliferation control (neoplastic tumour suppressor). In mitotic neuroblasts and other dividing cells, cortical Dlg is recruited by Aurora-A-phosphorylated Pins and couples it to the kinesin Khc-73 and astral microtubules to orient the spindle; it also maintains cortical Lgl for basal determinant targeting. At the larval neuromuscular junction Dlg is the principal postsynaptic scaffold of the subsynaptic reticulum. It clusters Fas2 and Shaker channels through PDZ binding, recruits Scrib via GukH, and stabilizes GluRIIB-containing glutamate receptors; PAR-1 phosphorylation controls its synaptic targeting. The DlgS97 isoform is required for adult synapse function and complex behaviours.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IGI PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | ACCEPT | Summary: IGI with Ran in induced-polarity S2 cells: dlg and ran double knockdown worsens spindle orientation more than ran alone, placing Dlg in the PinsLINKER/Dlg/Khc-73 branch parallel to Canoe/Ran/Mud. Reason: Dlg is the cortical adaptor that couples phosphorylated Pins to the kinesin Khc-73 and astral microtubules; this is a direct mechanistic role in mitotic spindle orientation, established in S2 cells and neuroblasts. Supporting Evidence: PMID:22024168 double RNAi knockdowns of ran and the PinsLINKER pathway component dlg led to a more severe spindle orientation phenotype than ran RNAi alone PMID:19766567 We conclude that the PinsLINKER recruits Dlg to the cortex, where the DlgGK domain promotes spindle orientation. PMID:16377571 Khc-73 localizes to astral microtubule plus ends, and Dlg/Khc-73 and Dlg/Pins coimmunoprecipitate, suggesting that microtubules induce Pins/Galphai cortical polarity through Dlg/Khc-73 interactions. |
| GO:0001708 cell fate specification | IMP PMID:19948068 Role of Scrib and Dlg in anterior-posterior patterning of th... | MARK AS OVER ANNOTATED | Summary: Loss of dlg in posterior follicle cells abolishes posterior follicle cell fate. Reason: The fate defect follows from disrupted epithelial polarity and the resulting failure of coordinated EGFR, JAK/STAT and Notch signalling. Dlg does not specify fate itself; it maintains the polarized epithelium that the signals act in. Supporting Evidence: PMID:19948068 Further, we showed that the aberrant coordinated activities of EGFR, JAK/STAT and Notch pathways elicited by mutations in scrib/dlg are causally linked to defective specification of the PFC fate in the mosaic clones. PMID:19948068 removal of scrib or dlg function from the follicle cells at posterior terminal of the egg chamber causes a complete loss of the PFC fate |
| GO:0001738 morphogenesis of a polarized epithelium | TAS PMID:14644201 Apicobasal polarization: epithelial form and function. | KEEP AS NON CORE | Summary: TAS from a general review of apicobasal polarization that does not discuss Dlg specifically. Reason: Dlg is required for epithelial apicobasal polarity and septate junction integrity, so it contributes to forming polarized epithelia. The process term is broad and developmental; the core claim is better captured by the epithelial polarity term. Supporting Evidence: PMID:8830775 the Dlg protein is a critical component of the septate junctions and is required for maintaining apicobasal polarity in Drosophila epithelium PMID:10884224 Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control. |
| GO:0004385 GMP kinase activity | TAS PMID:10458610 Regulation of DLG localization at synapses by CaMKII-depende... | REMOVE | Summary: TAS asserting GMP kinase (guanylate kinase) activity, based on homology of the Dlg C-terminal GUK domain to guanylate kinases. Reason: The MAGUK GUK domain is a protein-interaction domain that lost catalytic activity during evolution. Ancestral reconstruction shows the GK protein-interaction domain gained Pins binding as enzyme activity was lost. The Dlg GUK binds GukH and Pins. No assay has shown Dlg phosphorylating GMP. Supporting Evidence: PMID:26740169 Specifically, we found that Anc-GK1PID has no detectable guanylate kinase activity, but it binds Pins with moderate affinity and is highly effective in orienting the mitotic spindle in cell culture PMID:19769408 Membrane-associated guanylate kinases (MAGUKs) organize protein complexes at specific cellular sites by regulating interactions with their COOH-terminal guanylate kinase-like domains (GKs). PMID:11937021 Here we report the isolation of a new DLG-interacting protein, GUK-holder, that interacts with the GUK domain of DLG and which is dynamically expressed during synaptic bouton budding. |
| GO:0004385 GMP kinase activity | TAS PMID:11117747 Role of cortical tumour-suppressor proteins in asymmetric di... | REMOVE | Summary: TAS asserting GMP kinase (guanylate kinase) activity, based on homology of the Dlg C-terminal GUK domain to guanylate kinases. Reason: The MAGUK GUK domain is a protein-interaction domain that lost catalytic activity during evolution. Ancestral reconstruction shows the GK protein-interaction domain gained Pins binding as enzyme activity was lost. The Dlg GUK binds GukH and Pins. No assay has shown Dlg phosphorylating GMP. Supporting Evidence: PMID:26740169 Specifically, we found that Anc-GK1PID has no detectable guanylate kinase activity, but it binds Pins with moderate affinity and is highly effective in orienting the mitotic spindle in cell culture PMID:19769408 Membrane-associated guanylate kinases (MAGUKs) organize protein complexes at specific cellular sites by regulating interactions with their COOH-terminal guanylate kinase-like domains (GKs). PMID:11937021 Here we report the isolation of a new DLG-interacting protein, GUK-holder, that interacts with the GUK domain of DLG and which is dynamically expressed during synaptic bouton budding. |
| GO:0005515 protein binding | IPI PMID:11937021 Recruitment of scribble to the synaptic scaffolding complex ... | REMOVE | Summary: IPI: Dlg interacts with GUK-holder (GukH) through its GUK domain. Reason: Bare protein binding is uninformative. The GUK-GukH interaction is real and is captured in the core function as part of Dlg's scaffold role; there is no more specific MF term for this contact. Supporting Evidence: PMID:11937021 Here we report the isolation of a new DLG-interacting protein, GUK-holder, that interacts with the GUK domain of DLG and which is dynamically expressed during synaptic bouton budding. |
| GO:0005515 protein binding | IPI PMID:11937021 Recruitment of scribble to the synaptic scaffolding complex ... | MODIFY | Summary: IPI: Dlg binds the C-terminus of the Shaker K+ channel. Reason: Binding to the Shaker channel C-terminus through Dlg PDZ domains is the basis of Dlg-dependent channel clustering. The informative term is transmembrane transporter binding (formerly ion channel binding), not bare protein binding. Proposed replacements: transmembrane transporter binding Supporting Evidence: PMID:9390515 the PDZ-containing protein Discs-Large (Dlg) controls the localization of these proteins, most likely through a direct interaction with their C-terminal amino acids |
| GO:0005515 protein binding | IPI PMID:11937021 Recruitment of scribble to the synaptic scaffolding complex ... | REMOVE | Summary: IPI: Dlg interacts with GUK-holder (GukH) through its GUK domain. Reason: Bare protein binding is uninformative. The GUK-GukH interaction is real and is captured in the core function as part of Dlg's scaffold role; there is no more specific MF term for this contact. Supporting Evidence: PMID:11937021 Here we report the isolation of a new DLG-interacting protein, GUK-holder, that interacts with the GUK domain of DLG and which is dynamically expressed during synaptic bouton budding. |
| GO:0005515 protein binding | IPI PMID:17666528 Intrinsic disorder in the C-terminal domain of the Shaker vo... | MODIFY | Summary: IPI: Shaker C-terminal segment binds its PDZ scaffold partner. Reason: The interaction is the PDZ-mediated binding of a Kv channel C-terminus to the MAGUK scaffold. Transmembrane transporter binding is the informative MF. Proposed replacements: transmembrane transporter binding Supporting Evidence: PMID:17666528 We show that isolated ShB-C is still able to bind its scaffold protein partner and support protein clustering in vivo PMID:9390515 the PDZ-containing protein Discs-Large (Dlg) controls the localization of these proteins, most likely through a direct interaction with their C-terminal amino acids |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm, transferred from mammalian DLG1 or from the UniProt subcellular location keyword. Reason: Dlg is a peripheral membrane protein on the cytoplasmic face of the plasma membrane, so it is cytoplasmic in the broad sense. FRAP shows a mobile extrasynaptic pool in muscle that feeds synaptic Dlg. Its functional locations are junctional and postsynaptic membranes. Supporting Evidence: file:DROME/dlg1/dlg1-uniprot.txt Note=Cytoskeleton- and membrane- associated. Located at the cytoplasmic face of the membrane in the cellular blastoderm |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cytoplasm, transferred from mammalian DLG1 or from the UniProt subcellular location keyword. Reason: Dlg is a peripheral membrane protein on the cytoplasmic face of the plasma membrane, so it is cytoplasmic in the broad sense. FRAP shows a mobile extrasynaptic pool in muscle that feeds synaptic Dlg. Its functional locations are junctional and postsynaptic membranes. Supporting Evidence: file:DROME/dlg1/dlg1-uniprot.txt Note=Cytoskeleton- and membrane- associated. Located at the cytoplasmic face of the membrane in the cellular blastoderm |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Cytoskeleton, from the UniProt subcellular location line (cytoskeleton- and membrane-associated). Reason: Dlg is a cortical, membrane-associated scaffold. It is needed for normal cytoskeletal organization, but no evidence shows it is a component of the cytoskeleton. Cell cortex and septate junction describe its location better. Supporting Evidence: PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure file:DROME/dlg1/dlg1-uniprot.txt Note=Cytoskeleton- and membrane- associated. Located at the cytoplasmic face of the membrane in the cellular blastoderm |
| GO:0005886 plasma membrane | EXP PMID:10884224 Cooperative regulation of cell polarity and growth by Drosop... | ACCEPT | Summary: Dlg localizes to the junctional region of the lateral plasma membrane in embryonic, imaginal disc and follicle epithelia. Reason: Dlg is a peripheral plasma-membrane scaffold in epithelia, the cellularizing embryo, muscle and neuroblasts. Plasma membrane association is a core, correct claim across these cell types; the cell-type-specific sub-membranes (lateral, basolateral, postsynaptic) are annotated and accepted in their own rows. Supporting Evidence: PMID:10884224 Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. |
| GO:0005886 plasma membrane | EXP PMID:1651169 The discs-large tumor suppressor gene of Drosophila encodes ... | ACCEPT | Summary: Immunolocalization at the septate junction in an apical belt of the lateral membrane. Reason: Dlg is a peripheral plasma-membrane scaffold in epithelia, the cellularizing embryo, muscle and neuroblasts. Plasma membrane association is a core, correct claim across these cell types; the cell-type-specific sub-membranes (lateral, basolateral, postsynaptic) are annotated and accepted in their own rows. Supporting Evidence: PMID:1651169 the dlg gene product is localized in an apical belt of the lateral cell membrane, at the position of the septate junction |
| GO:0005886 plasma membrane | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: HDA: YFP-trap screen of follicle cells; Dlg insertions localize laterally. Reason: Dlg is a peripheral plasma-membrane scaffold in epithelia, the cellularizing embryo, muscle and neuroblasts. Plasma membrane association is a core, correct claim across these cell types; the cell-type-specific sub-membranes (lateral, basolateral, postsynaptic) are annotated and accepted in their own rows. Supporting Evidence: PMID:25294944 From those, Dlg is a known marker of the lateral membrane |
| GO:0005886 plasma membrane | HDA PMID:26896675 A genome-wide resource for the analysis of protein localisat... | ACCEPT | Summary: HDA: fosmid-tagged Dlg1-GFP in adult muscle labels T-tubular membranes. Reason: Dlg is a peripheral plasma-membrane scaffold in epithelia, the cellularizing embryo, muscle and neuroblasts. Plasma membrane association is a core, correct claim across these cell types; the cell-type-specific sub-membranes (lateral, basolateral, postsynaptic) are annotated and accepted in their own rows. Supporting Evidence: PMID:26896675 Dlg1-GFP labels the T-tubular membranes |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location 'Cell membrane; peripheral membrane protein; cytoplasmic side'. Reason: Dlg is a peripheral plasma-membrane scaffold in epithelia, the cellularizing embryo, muscle and neuroblasts. Plasma membrane association is a core, correct claim across these cell types; the cell-type-specific sub-membranes (lateral, basolateral, postsynaptic) are annotated and accepted in their own rows. Supporting Evidence: PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure |
| GO:0005886 plasma membrane | IMP PMID:14562058 Discs-Large and Strabismus are functionally linked to plasma... | ACCEPT | Summary: Dlg is distributed along the plasma membrane at cell-cell contacts during cellularization, and Stbm is required for this. Reason: Dlg is a peripheral plasma-membrane scaffold in epithelia, the cellularizing embryo, muscle and neuroblasts. Plasma membrane association is a core, correct claim across these cell types; the cell-type-specific sub-membranes (lateral, basolateral, postsynaptic) are annotated and accepted in their own rows. Supporting Evidence: PMID:14562058 In control CS embryos, however, Dlg was distributed continuously along the plasma membrane at regions of cell–cell contact, and Dlt was enriched at invaginating cleavage furrows |
| GO:0005918 septate junction | IDA PMID:17032735 Gliotactin and Discs large form a protein complex at the tri... | ACCEPT | Summary: Dlg localizes to the septate junction. Reason: Septate junction localization is the defining epithelial location of Dlg and is where it acts to maintain the junction and polarity. Supporting Evidence: PMID:1651169 the dlg gene product is localized in an apical belt of the lateral cell membrane, at the position of the septate junction PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure |
| GO:0005918 septate junction | IEA GO_REF:0000044 | ACCEPT | Summary: Dlg localizes to the septate junction. Reason: Septate junction localization is the defining epithelial location of Dlg and is where it acts to maintain the junction and polarity. Supporting Evidence: PMID:1651169 the dlg gene product is localized in an apical belt of the lateral cell membrane, at the position of the septate junction PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure |
| GO:0005920 smooth septate junction | IDA PMID:22854041 A novel protein complex, Mesh-Ssk, is required for septate j... | KEEP AS NON CORE | Summary: IDA: Dlg detected at smooth septate junctions of the midgut (abstract-only cache). Reason: Full text not cached. The cached abstract does not mention Dlg, but the curator read the full paper and Dlg is a general septate junction scaffold. Kept as a correct but peripheral location. Supporting Evidence: PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure |
| GO:0005938 cell cortex | IDA PMID:11117747 Role of cortical tumour-suppressor proteins in asymmetric di... | ACCEPT | Summary: Dlg is cortical in mitotic neuroblasts and needed for cortical Lgl. Reason: Cortical localization in neuroblasts is where Dlg acts in basal protein targeting and Pins/Galphai polarity. Supporting Evidence: PMID:11117747 Another tumour-suppressor protein, Lethal discs large (Dlg), participates in this process by regulating the localization of Lgl. PMID:12545176 Dlg/Scrib/Lgl proteins show apical cortical enrichment at prophase/metaphase, and then have a uniform cortical distribution. |
| GO:0005938 cell cortex | IDA PMID:12545176 Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic... | ACCEPT | Summary: Dlg is apically enriched then uniformly cortical in neuroblasts. Reason: Direct localization evidence for the neuroblast cortex. Supporting Evidence: PMID:12545176 Dlg/Scrib/Lgl proteins show apical cortical enrichment at prophase/metaphase, and then have a uniform cortical distribution. |
| GO:0007163 establishment or maintenance of cell polarity | NAS PMID:32414916 Distinct activities of Scrib module proteins organize epithe... | MODIFY | Summary: NAS from a study of Scrib module activities in follicle epithelium. Reason: Correct but general. The work concerns epithelial apicobasal polarity, and the gene carries the more specific epithelial polarity term via IBA. Proposed replacements: establishment or maintenance of epithelial cell apical/basal polarity Supporting Evidence: PMID:32414916 Cortical recruitment of Scrib does not require palmitoylation or polar phospholipid binding but instead an independent cortically stabilizing activity of Dlg. |
| GO:0007268 chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dlg is needed for normal synaptic transmission at the larval NMJ. Reason: Dlg shapes synaptic transmission as a postsynaptic scaffold that sets glutamate receptor subunit composition and synapse structure; it is not part of the transmitter release or receptor machinery. Kept as a broad non-core process. Supporting Evidence: PMID:15638945 Our results suggest that DLG controls glutamate receptor subunit composition by selectively stabilizing GluRIIB-containing receptors at the synapse. PMID:17224403 Thus, PAR-1 overactivation or Dlg loss of function reduced EJC amplitude, whereas loss of PAR-1 had the opposite effect. |
| GO:0007268 chemical synaptic transmission | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Dlg is needed for normal synaptic transmission at the larval NMJ. Reason: Dlg shapes synaptic transmission as a postsynaptic scaffold that sets glutamate receptor subunit composition and synapse structure; it is not part of the transmitter release or receptor machinery. Kept as a broad non-core process. Supporting Evidence: PMID:15638945 Our results suggest that DLG controls glutamate receptor subunit composition by selectively stabilizing GluRIIB-containing receptors at the synapse. PMID:17224403 Thus, PAR-1 overactivation or Dlg loss of function reduced EJC amplitude, whereas loss of PAR-1 had the opposite effect. |
| GO:0007268 chemical synaptic transmission | IMP PMID:10458610 Regulation of DLG localization at synapses by CaMKII-depende... | KEEP AS NON CORE | Summary: dlg mutants alter synaptic structure and function at the NMJ. Reason: Real phenotype, but it acts through Dlg's scaffold role in synapse assembly and receptor localization. Supporting Evidence: PMID:10458610 In this paper we have established a close functional link between changes in CaMKII activity and the involvement of the Drosophila MAGUK DLG in the process of synapse assembly. PMID:15638945 Our results suggest that DLG controls glutamate receptor subunit composition by selectively stabilizing GluRIIB-containing receptors at the synapse. |
| GO:0007268 chemical synaptic transmission | IMP PMID:12451127 Quantal size and variation determined by vesicle size in nor... | KEEP AS NON CORE | Summary: dlg mutants have altered synaptic vesicle size and quantal size. Reason: Indirect effect on transmission via synapse organization; kept as non-core. Supporting Evidence: PMID:12451127 The same finding applied to two mutants (dlg and lap) in which synaptic vesicle size was altered. |
| GO:0007318 germ plasm protein localization | IMP PMID:19948068 Role of Scrib and Dlg in anterior-posterior patterning of th... | MARK AS OVER ANNOTATED | Summary: Staufen is mislocalized in the oocyte when posterior follicle cells lack dlg. Reason: This is a non-cell-autonomous consequence of failed posterior follicle cell specification. Dlg does not act in germline protein localization. Supporting Evidence: PMID:19948068 Since proper differentiation of the PFCs is essential for reorganization of the microtubule cytoskeleton in the oocyte, hence for the oocyte polarity formation, it is deducible that mutations in scrib/dlg can cause defective microtubule polarization and oocyte polarity at mid-oogenesis. |
| GO:0007391 dorsal closure | TAS PMID:10449347 Roles of the JNK signaling pathway in Drosophila morphogenes... | UNDECIDED | Summary: TAS citing a review of JNK signalling in morphogenesis that does not mention Dlg. Reason: The cited review does not discuss dlg, so the statement cannot be traced to evidence here. |
| GO:0007399 nervous system development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dlg is required for neural development (isoform-specific neuronal roles). Reason: Dlg acts in neuroblast asymmetric division and synapse development, which sit under this broad term. Kept as non-core. Supporting Evidence: PMID:11117747 Another tumour-suppressor protein, Lethal discs large (Dlg), participates in this process by regulating the localization of Lgl. PMID:17224403 In a severe dlg semi-lethal mutant dlg X1-2 , loss of Dlg leads to a significant decrease of bouton number and simplification of synapse morphology |
| GO:0007399 nervous system development | IMP PMID:11117747 Role of cortical tumour-suppressor proteins in asymmetric di... | KEEP AS NON CORE | Summary: Dlg is required for neural development (isoform-specific neuronal roles). Reason: Dlg acts in neuroblast asymmetric division and synapse development, which sit under this broad term. Kept as non-core. Supporting Evidence: PMID:11117747 Another tumour-suppressor protein, Lethal discs large (Dlg), participates in this process by regulating the localization of Lgl. PMID:17224403 In a severe dlg semi-lethal mutant dlg X1-2 , loss of Dlg leads to a significant decrease of bouton number and simplification of synapse morphology |
| GO:0007617 mating behavior | IMP PMID:18171947 DLGS97/SAP97 is developmentally upregulated and is required ... | KEEP AS NON CORE | Summary: dlgS97 mutants show defects in complex adult behaviours. Reason: Behavioural phenotypes of an isoform-specific null, probably via synaptic scaffolding in adult brain circuits. Kept as non-core. Supporting Evidence: PMID:18171947 dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship |
| GO:0008049 male courtship behavior | IMP PMID:18171947 DLGS97/SAP97 is developmentally upregulated and is required ... | KEEP AS NON CORE | Summary: dlgS97 mutants show defects in complex adult behaviours. Reason: Behavioural phenotypes of an isoform-specific null, probably via synaptic scaffolding in adult brain circuits. Kept as non-core. Supporting Evidence: PMID:18171947 dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship |
| GO:0009792 embryo development ending in birth or egg hatching | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA-predicted embryo development. Reason: Broad rule-based prediction. Dlg does have embryonic roles (epithelial polarity, neuroblast division), but these are covered by specific terms, and this uninformative ARBA term adds nothing. |
| GO:0010669 epithelial structure maintenance | ISS GO_REF:0000024 | ACCEPT | Summary: ISS: epithelial structure maintenance. Reason: Dlg is required to maintain septate junctions and apicobasal polarity in epithelia. Supporting Evidence: PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure PMID:8830775 the Dlg protein is a critical component of the septate junctions and is required for maintaining apicobasal polarity in Drosophila epithelium |
| GO:0016323 basolateral plasma membrane | EXP PMID:24768049 PI(4,5)P2 produced by the PI4P5K SKTL controls apical size b... | ACCEPT | Summary: Dlg localizes to the basolateral plasma membrane of epithelial cells. Reason: Core epithelial location of the Scrib module scaffold. Supporting Evidence: PMID:10884224 Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. PMID:25719210 These polarity regulators–scribble (scrib), discs-large (dlg), and lethal giant larvae (lgl)- cooperatively distinguish the basolateral domain from the apical by antagonizing aPKC activity |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Dlg localizes to the basolateral plasma membrane of epithelial cells. Reason: Core epithelial location of the Scrib module scaffold. Supporting Evidence: PMID:10884224 Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. PMID:25719210 These polarity regulators–scribble (scrib), discs-large (dlg), and lethal giant larvae (lgl)- cooperatively distinguish the basolateral domain from the apical by antagonizing aPKC activity |
| GO:0016323 basolateral plasma membrane | TAS PMID:14644201 Apicobasal polarization: epithelial form and function. | ACCEPT | Summary: Dlg localizes to the basolateral plasma membrane of epithelial cells. Reason: Core epithelial location of the Scrib module scaffold. Supporting Evidence: PMID:10884224 Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. PMID:25719210 These polarity regulators–scribble (scrib), discs-large (dlg), and lethal giant larvae (lgl)- cooperatively distinguish the basolateral domain from the apical by antagonizing aPKC activity |
| GO:0016327 apicolateral plasma membrane | IDA PMID:10884224 Cooperative regulation of cell polarity and growth by Drosop... | ACCEPT | Summary: Dlg colocalizes with Scrib at the apicolateral junctional region of epithelia. Reason: Matches the septate junction position of Dlg. Supporting Evidence: PMID:10884224 Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. PMID:1651169 the dlg gene product is localized in an apical belt of the lateral cell membrane, at the position of the septate junction |
| GO:0016328 lateral plasma membrane | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: HDA: Dlg-YFP is laterally localized in follicle cells. Reason: Consistent with Dlg as a lateral membrane marker. Supporting Evidence: PMID:25294944 From those, Dlg is a known marker of the lateral membrane |
| GO:0016328 lateral plasma membrane | IDA PMID:18501681 Temporal and spatial expression of Drosophila DLGS97 during ... | ACCEPT | Summary: DLGS97 localizes basal to the basolateral junctions in photoreceptors. Reason: Direct localization evidence. Supporting Evidence: PMID:18501681 During eye development DLGS97 starts to be expressed in photoreceptor cells at early stages of differentiation and localizes basal to the basolateral junctions. |
| GO:0016333 morphogenesis of follicular epithelium | IMP PMID:10884224 Cooperative regulation of cell polarity and growth by Drosop... | KEEP AS NON CORE | Summary: dlg mutant follicle cells lose polarity and become multilayered. Reason: Tissue-morphogenesis consequence of Dlg's polarity role. Supporting Evidence: PMID:10884224 We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia |
| GO:0016334 establishment or maintenance of polarity of follicular epithelium | IGI PMID:10884224 Cooperative regulation of cell polarity and growth by Drosop... | ACCEPT | Summary: dlg and lgl interact genetically in follicle epithelium polarity. Reason: Epithelial polarity is a core Dlg function. Supporting Evidence: PMID:10884224 Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control. |
| GO:0016335 morphogenesis of larval imaginal disc epithelium | TAS PMID:10884224 Cooperative regulation of cell polarity and growth by Drosop... | KEEP AS NON CORE | Summary: TAS: dlg mutant imaginal discs lose epithelial organization. Reason: Tissue-morphogenesis consequence of Dlg's polarity role. Supporting Evidence: PMID:10884224 We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia |
| GO:0016336 establishment or maintenance of polarity of larval imaginal disc epithelium | IMP PMID:25719210 The transcriptional response to tumorigenic polarity loss in... | ACCEPT | Summary: dlg loss disrupts wing disc epithelial architecture. Reason: Epithelial polarity in imaginal discs is a core Dlg function. Supporting Evidence: PMID:25719210 These polarity regulators–scribble (scrib), discs-large (dlg), and lethal giant larvae (lgl)- cooperatively distinguish the basolateral domain from the apical by antagonizing aPKC activity PMID:25719210 F-actin staining reveals dramatic overgrowth and architecture defects of neoplastic dlg and scrib wing discs relative to WT. |
| GO:0019900 kinase binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro-based kinase binding. Reason: Entailed by protein kinase binding, which is kept. |
| GO:0019901 protein kinase binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: protein kinase binding. Reason: MAGUKs bind kinases. DlgS97 binds the CASK homolog Caki through L27, and Dlg is a substrate of PAR-1 and CaMKII. This binding is real but not the core scaffold activity. Supporting Evidence: PMID:23145041 mutants in the gene calcium/calmodulin-dependent protein kinase (caki), encoding the fly homolog of mammalian CASK, a known binding partner of DlgS97 PMID:17224403 PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. |
| GO:0019991 septate junction assembly | TAS PMID:12141438 Genetic studies define MAGUK proteins as regulators of epith... | ACCEPT | Summary: TAS from reviews: Dlg is required for septate junction formation. Reason: Dlg is a cytoplasmic component of the septate junction and is required to form and maintain it, so it contributes structurally to the junction. Supporting Evidence: PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure PMID:17032735 We now show that Gliotactin associates with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is essential for the formation of the TCJ and the localization of Gliotactin. |
| GO:0019991 septate junction assembly | TAS PMID:12147138 Signaling pathways directing the movement and fusion of epit... | ACCEPT | Summary: TAS from reviews: Dlg is required for septate junction formation. Reason: Dlg is a cytoplasmic component of the septate junction and is required to form and maintain it, so it contributes structurally to the junction. Supporting Evidence: PMID:8830775 we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure PMID:17032735 We now show that Gliotactin associates with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is essential for the formation of the TCJ and the localization of Gliotactin. |
| GO:0030707 follicle cell of egg chamber development | IMP PMID:19948068 Role of Scrib and Dlg in anterior-posterior patterning of th... | KEEP AS NON CORE | Summary: dlg mosaic clones disrupt follicle cell differentiation. Reason: Developmental consequence of the polarity function. Supporting Evidence: PMID:19948068 removal of scrib or dlg function from the follicle cells at posterior terminal of the egg chamber causes a complete loss of the PFC fate |
| GO:0030714 anterior/posterior axis specification, follicular epithelium | IMP PMID:19948068 Role of Scrib and Dlg in anterior-posterior patterning of th... | MARK AS OVER ANNOTATED | Summary: dlg loss disrupts anterior-posterior patterning of the follicular epithelium. Reason: Patterning defects follow from polarity loss and the resulting signalling failures, so this is downstream of Dlg rather than something it does. Supporting Evidence: PMID:19948068 Further, we showed that the aberrant coordinated activities of EGFR, JAK/STAT and Notch pathways elicited by mutations in scrib/dlg are causally linked to defective specification of the PFC fate in the mosaic clones. |
| GO:0031256 leading edge membrane | IDA PMID:15056617 A Fasciclin 2 morphogenetic switch organizes epithelial cell... | KEEP AS NON CORE | Summary: Dlg localization in border cells is maintained by Fas2 signalling. Reason: Full text not cached. Dlg localizes in migrating border cells; the curator's leading-edge assignment is deferred to. Supporting Evidence: PMID:15056617 Fas2-mediated communication between polar and border cells maintains localization of Discs large and Lethal-giant-larvae in border cells to inhibit the rate of cluster migration. |
| GO:0031594 neuromuscular junction | IBA GO_REF:0000033 | ACCEPT | Summary: Dlg is a major scaffold at the larval neuromuscular junction, mostly postsynaptic. Reason: Core neuronal/muscle location of Dlg. Supporting Evidence: PMID:18070911 We found that both Fas2- and Dlg-GFP became concentrated at the presumptive postsynaptic site immediately after the formation of the synaptic contact site. PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0031594 neuromuscular junction | IDA PMID:18070911 In vivo induction of postsynaptic molecular assembly by the ... | ACCEPT | Summary: Dlg is a major scaffold at the larval neuromuscular junction, mostly postsynaptic. Reason: Core neuronal/muscle location of Dlg. Supporting Evidence: PMID:18070911 We found that both Fas2- and Dlg-GFP became concentrated at the presumptive postsynaptic site immediately after the formation of the synaptic contact site. PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0031594 neuromuscular junction | IDA PMID:30904609 Dystrobrevin is required postsynaptically for homeostatic po... | ACCEPT | Summary: Dlg is a major scaffold at the larval neuromuscular junction, mostly postsynaptic. Reason: Core neuronal/muscle location of Dlg. Supporting Evidence: PMID:18070911 We found that both Fas2- and Dlg-GFP became concentrated at the presumptive postsynaptic site immediately after the formation of the synaptic contact site. PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0031594 neuromuscular junction | IEA GO_REF:0000002 | ACCEPT | Summary: Dlg is a major scaffold at the larval neuromuscular junction, mostly postsynaptic. Reason: Core neuronal/muscle location of Dlg. Supporting Evidence: PMID:18070911 We found that both Fas2- and Dlg-GFP became concentrated at the presumptive postsynaptic site immediately after the formation of the synaptic contact site. PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0035418 protein localization to synapse | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: protein localization to synapse. Reason: Dlg controls synaptic localization of Fas2, Shaker and Scrib via PDZ and GUK interactions; it does the localizing work as the scaffold. Supporting Evidence: PMID:9390515 the PDZ-containing protein Discs-Large (Dlg) controls the localization of these proteins, most likely through a direct interaction with their C-terminal amino acids PMID:11937021 We show that DLG, GUKH, and SCRIB form a tripartite complex at synapses, in which DLG and GUKH are required for the proper synaptic localization of SCRIB. |
| GO:0042058 regulation of epidermal growth factor receptor signaling pathway | IMP PMID:19948068 Role of Scrib and Dlg in anterior-posterior patterning of th... | MARK AS OVER ANNOTATED | Summary: dlg clones show defective EGFR signalling in posterior follicle cells. Reason: The signalling defect is a secondary consequence of polarity loss in multilayered cells; Dlg is not a pathway component. Supporting Evidence: PMID:19948068 Further, we showed that the aberrant coordinated activities of EGFR, JAK/STAT and Notch pathways elicited by mutations in scrib/dlg are causally linked to defective specification of the PFC fate in the mosaic clones. |
| GO:0042332 gravitaxis | IMP PMID:16594976 Gravitaxis in Drosophila melanogaster: a forward genetic scr... | KEEP AS NON CORE | Summary: Gravitaxis screen mutant mapped to dlg (abstract-only cache). Reason: Full text not cached. A behavioural phenotype from a forward screen is deferred to the curator and kept as non-core. |
| GO:0042734 presynaptic membrane | IDA PMID:11937021 Recruitment of scribble to the synaptic scaffolding complex ... | KEEP AS NON CORE | Summary: Dlg colocalizes with presynaptic membrane at NMJ (Dlg is pre- and postsynaptic). Reason: Minor presynaptic pool; the major pool is postsynaptic. Supporting Evidence: PMID:11937021 We show that DLG, GUKH, and SCRIB form a tripartite complex at synapses, in which DLG and GUKH are required for the proper synaptic localization of SCRIB. |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neuron projection localization (axons and synaptic terminals). Reason: Dlg is present in axons and presynaptic terminals, but its best-characterized neuronal site is the postsynaptic SSR. Supporting Evidence: PMID:11937021 We show that DLG, GUKH, and SCRIB form a tripartite complex at synapses, in which DLG and GUKH are required for the proper synaptic localization of SCRIB. |
| GO:0043005 neuron projection | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Neuron projection localization (axons and synaptic terminals). Reason: Dlg is present in axons and presynaptic terminals, but its best-characterized neuronal site is the postsynaptic SSR. Supporting Evidence: PMID:11937021 We show that DLG, GUKH, and SCRIB form a tripartite complex at synapses, in which DLG and GUKH are required for the proper synaptic localization of SCRIB. |
| GO:0043113 receptor clustering | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: receptor clustering. Reason: Dlg clusters Shaker channels and Fas2 and stabilizes GluRIIB receptors at the synapse. Supporting Evidence: PMID:9390515 the PDZ-containing protein Discs-Large (Dlg) controls the localization of these proteins, most likely through a direct interaction with their C-terminal amino acids PMID:15638945 Our results suggest that DLG controls glutamate receptor subunit composition by selectively stabilizing GluRIIB-containing receptors at the synapse. |
| GO:0043195 terminal bouton | IDA PMID:11937021 Recruitment of scribble to the synaptic scaffolding complex ... | KEEP AS NON CORE | Summary: Dlg at terminal boutons, with GukH and Scrib. Reason: Correct; the bouton-associated pool is mainly in the surrounding postsynaptic SSR. Supporting Evidence: PMID:11937021 We show that DLG, GUKH, and SCRIB form a tripartite complex at synapses, in which DLG and GUKH are required for the proper synaptic localization of SCRIB. |
| GO:0043296 apical junction complex | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA-predicted apical junction complex. Reason: Drosophila Dlg is at the septate junction, basal to the adherens junction. In dlg mutants septate junctions are lost and ectopic adherens junctions appear, so Dlg is not part of an apical junction complex in the GO sense. Supporting Evidence: PMID:9144922 a loss-of-function dlg mutation, which causes neoplastic imaginal disc overgrowth, leads to loss of the septate junctions and the formation of what appear to be ectopic adherens junctions |
| GO:0043297 apical junction assembly | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA-predicted apical junction assembly. Reason: Dlg's junctional assembly role is septate junction assembly, which is annotated separately. Supporting Evidence: PMID:9144922 a loss-of-function dlg mutation, which causes neoplastic imaginal disc overgrowth, leads to loss of the septate junctions and the formation of what appear to be ectopic adherens junctions |
| GO:0045167 asymmetric protein localization involved in cell fate determination | IMP PMID:11117747 Role of cortical tumour-suppressor proteins in asymmetric di... | ACCEPT | Summary: Dlg is required for Lgl localization and basal targeting of determinants in neuroblasts. Reason: Dlg is part of the cortical machinery that targets Numb/Prospero basally in asymmetric neuroblast division. Supporting Evidence: PMID:11117747 Another tumour-suppressor protein, Lethal discs large (Dlg), participates in this process by regulating the localization of Lgl. |
| GO:0045175 basal protein localization | IMP PMID:11117748 The tumour-suppressor genes lgl and dlg regulate basal prote... | ACCEPT | Summary: dlg mutants fail basal protein targeting in neuroblasts. Reason: Direct requirement of cortical Dlg for basal protein targeting. Supporting Evidence: PMID:11117748 the tumour-suppressor genes lethal giant larvae (lgl) and discs large (dlg) regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts PMID:12545176 Mutants have defects in basal protein targeting, a reduced apical cortical domain and reduced apical spindle size. |
| GO:0045175 basal protein localization | IMP PMID:12545176 Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic... | ACCEPT | Summary: dlg mutants fail basal protein targeting in neuroblasts. Reason: Direct requirement of cortical Dlg for basal protein targeting. Supporting Evidence: PMID:11117748 the tumour-suppressor genes lethal giant larvae (lgl) and discs large (dlg) regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts PMID:12545176 Mutants have defects in basal protein targeting, a reduced apical cortical domain and reduced apical spindle size. |
| GO:0045179 apical cortex | IDA PMID:11117748 The tumour-suppressor genes lgl and dlg regulate basal prote... | KEEP AS NON CORE | Summary: Dlg is apically enriched in mitotic neuroblasts. Reason: Dlg is apically enriched in neuroblasts only transiently (prophase/metaphase) before becoming uniformly cortical, and in disc epithelia the apical-most Dlg is the apicolateral septate junction region. The apical cortex is a correct but peripheral location; cell cortex is the core neuroblast location. Supporting Evidence: PMID:11117748 Dlg protein is apically enriched and is required for maintaining cortical localization of Lgl protein. PMID:12545176 Dlg/Scrib/Lgl proteins show apical cortical enrichment at prophase/metaphase, and then have a uniform cortical distribution. |
| GO:0045179 apical cortex | IDA PMID:16377571 Microtubule-induced Pins/Galphai cortical polarity in Drosop... | KEEP AS NON CORE | Summary: Dlg forms a cortical crescent with Pins/Galphai in neuroblasts. Reason: Dlg is apically enriched in neuroblasts only transiently (prophase/metaphase) before becoming uniformly cortical, and in disc epithelia the apical-most Dlg is the apicolateral septate junction region. The apical cortex is a correct but peripheral location; cell cortex is the core neuroblast location. Supporting Evidence: PMID:16377571 We show that astral microtubules, kinesin Khc-73, and Discs large (Dlg) induce cortical polarization of Pins/Galphai in Drosophila neuroblasts |
| GO:0045179 apical cortex | IDA PMID:29378849 Drosophila melanogaster Guk-holder interacts with the Scribb... | KEEP AS NON CORE | Summary: Dlg co-localizes with Gukh and Scrib at the 'apical cortex' of wing and eye disc epithelia. Reason: Dlg is apically enriched in neuroblasts only transiently (prophase/metaphase) before becoming uniformly cortical, and in disc epithelia the apical-most Dlg is the apicolateral septate junction region. The apical cortex is a correct but peripheral location; cell cortex is the core neuroblast location. Supporting Evidence: PMID:29378849 In the larval-wing epithelium, Gukh was localized cortically and enriched apically, co-localizing with Dlg and Scrib in the apical cortex |
| GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: establishment or maintenance of epithelial cell apical/basal polarity. Reason: Core function: Dlg with Scrib and Lgl defines the basolateral domain. Supporting Evidence: PMID:10884224 Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control. PMID:32414916 Cortical recruitment of Scrib does not require palmitoylation or polar phospholipid binding but instead an independent cortically stabilizing activity of Dlg. |
| GO:0045202 synapse | IDA PMID:17224403 PAR-1 kinase phosphorylates Dlg and regulates its postsynapt... | MODIFY | Summary: Dlg localizes to the NMJ synapse, where PAR-1 controls its postsynaptic targeting. Reason: Correct but general; the study addresses postsynaptic Dlg. Proposed replacements: postsynaptic membrane Supporting Evidence: PMID:17224403 PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. |
| GO:0045211 postsynaptic membrane | IDA PMID:16413491 Synaptic protein synthesis associated with memory is regulat... | ACCEPT | Summary: Dlg localizes to the postsynaptic membrane. Reason: Core postsynaptic location. Supporting Evidence: PMID:18070911 We found that both Fas2- and Dlg-GFP became concentrated at the presumptive postsynaptic site immediately after the formation of the synaptic contact site. |
| GO:0045211 postsynaptic membrane | IDA PMID:18070911 In vivo induction of postsynaptic molecular assembly by the ... | ACCEPT | Summary: Dlg localizes to the postsynaptic membrane. Reason: Core postsynaptic location. Supporting Evidence: PMID:18070911 We found that both Fas2- and Dlg-GFP became concentrated at the presumptive postsynaptic site immediately after the formation of the synaptic contact site. |
| GO:0045475 locomotor rhythm | IMP PMID:18171947 DLGS97/SAP97 is developmentally upregulated and is required ... | KEEP AS NON CORE | Summary: dlgS97 mutants show defects in complex adult behaviours. Reason: Behavioural phenotypes of an isoform-specific null, probably via synaptic scaffolding in adult brain circuits. Kept as non-core. Supporting Evidence: PMID:18171947 dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship |
| GO:0045571 negative regulation of imaginal disc growth | IMP PMID:29719260 Yorkie and JNK Control Tumorigenesis in Drosophila Cells wit... | KEEP AS NON CORE | Summary: IMP: negative regulation of imaginal disc growth (tumour suppressor phenotype). Reason: The cached abstract does not mention dlg, so the curator's reading is deferred to. Classic neoplastic overgrowth follows polarity loss, so this is non-core. Supporting Evidence: PMID:8830775 the Dlg protein is a critical component of the septate junctions and is required for maintaining apicobasal polarity in Drosophila epithelium |
| GO:0045887 positive regulation of synaptic assembly at neuromuscular junction | IMP PMID:19244343 Syndapin promotes formation of a postsynaptic membrane syste... | KEEP AS NON CORE | Summary: Dlg is a known regulator of SSR development. Reason: Supported for SSR; kept non-core in favour of the direct synapse assembly row. Supporting Evidence: PMID:19244343 Syndapin can expand the SSR in the absence of dPAK and Dlg, two known regulators of SSR development. PMID:27838296 Discs large (Dlg), a key protein that assembles the subsynaptic reticulum (SSR) in Type 1b boutons |
| GO:0046037 GMP metabolic process | IEA GO_REF:0000108 | REMOVE | Summary: IEA from the GMP kinase activity mapping. Reason: Derived from the GMP kinase activity claim, which is removed because the MAGUK GUK domain is non-catalytic. Supporting Evidence: PMID:26740169 Specifically, we found that Anc-GK1PID has no detectable guanylate kinase activity, but it binds Pins with moderate affinity and is highly effective in orienting the mitotic spindle in cell culture |
| GO:0046710 GDP metabolic process | IEA GO_REF:0000108 | REMOVE | Summary: IEA from the GMP kinase activity mapping. Reason: Derived from the GMP kinase activity claim, which is removed because the MAGUK GUK domain is non-catalytic. Supporting Evidence: PMID:26740169 Specifically, we found that Anc-GK1PID has no detectable guanylate kinase activity, but it binds Pins with moderate affinity and is highly effective in orienting the mitotic spindle in cell culture |
| GO:0046956 positive phototaxis | IMP PMID:18171947 DLGS97/SAP97 is developmentally upregulated and is required ... | KEEP AS NON CORE | Summary: dlgS97 mutants show defects in complex adult behaviours. Reason: Behavioural phenotypes of an isoform-specific null, probably via synaptic scaffolding in adult brain circuits. Kept as non-core. Supporting Evidence: PMID:18171947 dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship |
| GO:0048149 behavioral response to ethanol | IMP PMID:23145041 DlgS97/SAP97, a neuronal isoform of discs large, regulates e... | KEEP AS NON CORE | Summary: DlgS97 is required for ethanol tolerance. Reason: Behavioural phenotype; non-core. Supporting Evidence: PMID:23145041 Ethanol tolerance in the intol mutant could be partially restored by transgenic expression of DlgS97, but not DlgA, in specific neurons of the fly's brain. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:18501681 Temporal and spatial expression of Drosophila DLGS97 during ... | KEEP AS NON CORE | Summary: DLGS97 is detected in the perinuclear cytoplasm of neurons. Reason: Minor location, probably biosynthetic or trafficking pool. |
| GO:0051124 synaptic assembly at neuromuscular junction | IMP PMID:17224403 PAR-1 kinase phosphorylates Dlg and regulates its postsynapt... | ACCEPT | Summary: dlg mutants have fewer boutons and simplified NMJs. Reason: Dlg is the scaffold that assembles the postsynaptic SSR, so it contributes structurally to NMJ assembly. Supporting Evidence: PMID:17224403 In a severe dlg semi-lethal mutant dlg X1-2 , loss of Dlg leads to a significant decrease of bouton number and simplification of synapse morphology PMID:27838296 Discs large (Dlg), a key protein that assembles the subsynaptic reticulum (SSR) in Type 1b boutons |
| GO:0051294 establishment of spindle orientation | IMP PMID:16377571 Microtubule-induced Pins/Galphai cortical polarity in Drosop... | MODIFY | Summary: Dlg is required for Pins/Galphai cortical polarity and spindle asymmetry in neuroblasts. Reason: Correct but general: neuroblast division is mitotic, and the gene already carries establishment of mitotic spindle orientation. Proposed replacements: establishment of mitotic spindle orientation Supporting Evidence: PMID:16377571 Khc-73 localizes to astral microtubule plus ends, and Dlg/Khc-73 and Dlg/Pins coimmunoprecipitate, suggesting that microtubules induce Pins/Galphai cortical polarity through Dlg/Khc-73 interactions. PMID:19766567 We conclude that the PinsLINKER recruits Dlg to the cortex, where the DlgGK domain promotes spindle orientation. |
| GO:0060581 cell fate commitment involved in pattern specification | IMP PMID:19948068 Role of Scrib and Dlg in anterior-posterior patterning of th... | MARK AS OVER ANNOTATED | Summary: Loss of dlg disrupts follicle cell fate commitment. Reason: Downstream of polarity loss, as for the other fate rows from this paper. Supporting Evidence: PMID:19948068 Further, we showed that the aberrant coordinated activities of EGFR, JAK/STAT and Notch pathways elicited by mutations in scrib/dlg are causally linked to defective specification of the PFC fate in the mosaic clones. |
| GO:0061060 negative regulation of peptidoglycan recognition protein signaling pathway | IMP PMID:27893816 miR-34 Modulates Innate Immunity and Ecdysone Signaling in D... | MARK AS OVER ANNOTATED | Summary: dlg1 RNAi in S2 cells mildly raises Diptericin; dlg1 is a miR-34 target. Reason: Weak RNAi effect in cultured cells with no mechanism. The authors call dlg1 only a candidate target that could potentially downregulate IMD signalling. Supporting Evidence: PMID:27893816 While the magnitude of changes in Diptericin expression upon silencing of individual genes appears to be weaker than that elicited by miR-34 overexpression, possibly due to low knockdown efficiency and/or slow turnover of target proteins, these data nonetheless suggest that CG8468, dlg1 and mura are candidate miR-34 target genes that could potentially downregulate IMD signaling. |
| GO:0061174 type I terminal bouton | IDA PMID:24046358 Fragile X mental retardation protein regulates trans-synapti... | KEEP AS NON CORE | Summary: Dlg at type I boutons (marker usage). Reason: Correct; Dlg is the standard postsynaptic marker of type I boutons. Supporting Evidence: PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0061176 type Ib terminal bouton | IDA PMID:15541314 The translational repressor Pumilio regulates presynaptic mo... | KEEP AS NON CORE | Summary: Dlg at type Ib boutons. Reason: Correct; Dlg surrounds type Ib boutons in the SSR. Supporting Evidence: PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0061689 tricellular tight junction | IDA PMID:17032735 Gliotactin and Discs large form a protein complex at the tri... | KEEP AS NON CORE | Summary: Dlg associates with Gliotactin at the tricellular junction. Reason: Direct evidence that Dlg is at the TCJ. In Drosophila this junction is septate-junction-derived, and the location is peripheral to Dlg's main septate junction role. Supporting Evidence: PMID:17032735 We now show that Gliotactin associates with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is essential for the formation of the TCJ and the localization of Gliotactin. |
| GO:0071212 subsynaptic reticulum | IDA PMID:27838296 Neurexin, Neuroligin and Wishful Thinking coordinate synapti... | ACCEPT | Summary: Dlg localizes to the subsynaptic reticulum. Reason: Core postsynaptic location; Dlg assembles the SSR. Supporting Evidence: PMID:27838296 Discs large (Dlg), a key protein that assembles the subsynaptic reticulum (SSR) in Type 1b boutons PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0097120 receptor localization to synapse | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: receptor localization to synapse. Reason: Dlg stabilizes GluRIIB-containing receptors and Shaker at the NMJ. Supporting Evidence: PMID:15638945 Our results suggest that DLG controls glutamate receptor subunit composition by selectively stabilizing GluRIIB-containing receptors at the synapse. PMID:9390515 the PDZ-containing protein Discs-Large (Dlg) controls the localization of these proteins, most likely through a direct interaction with their C-terminal amino acids |
| GO:0098609 cell-cell adhesion | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA: cell-cell adhesion. Reason: Dlg is a cytoplasmic scaffold and does not mediate adhesion itself. dlg loss converts septate junctions to ectopic adherens-like junctions rather than abolishing adhesion. Dlg binds the adhesion molecule Fas2 to localize it, which is captured by the synaptic localization terms. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN001136892 SUPPORTS SOURCE BUT NOT TARGET Node seeded by human DLG1 (Q12959) and SCRIB (Q14160) adhesion-related annotations; for fly Dlg the scaffold localizes adhesion molecules rather than mediating adhesion. Supporting Evidence: PMID:9144922 a loss-of-function dlg mutation, which causes neoplastic imaginal disc overgrowth, leads to loss of the septate junctions and the formation of what appear to be ectopic adherens junctions PMID:9390515 the PDZ-containing protein Discs-Large (Dlg) controls the localization of these proteins, most likely through a direct interaction with their C-terminal amino acids |
| GO:0098839 postsynaptic density membrane | IBA GO_REF:0000033 | MODIFY | Summary: IBA: postsynaptic density membrane. Reason: The Drosophila NMJ has no vertebrate-type PSD; Dlg is in the postsynaptic membrane and SSR. The PSD membrane is a vertebrate-ortholog over-specification. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000563569 SUPPORTS SOURCE BUT NOT TARGET Node grounded by rat PSD-95-family members at vertebrate PSDs; the Drosophila glutamatergic NMJ postsynapse is described as postsynaptic membrane/SSR. Proposed replacements: postsynaptic membrane Supporting Evidence: PMID:27838296 Dlg localizes to an intricate system of highly convoluted membrane, called the SSR that surrounds the postsynaptic muscle of the Type 1b boutons. |
| GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: regulation of postsynaptic membrane neurotransmitter receptor levels. Reason: Dlg sets GluRIIB receptor levels at the NMJ. Supporting Evidence: PMID:15638945 Our results suggest that DLG controls glutamate receptor subunit composition by selectively stabilizing GluRIIB-containing receptors at the synapse. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:19766567 Identification of an Aurora-A/PinsLINKER/Dlg spindle orienta... | NEW | Summary: Dlg bridges cortical phospho-Pins (via its GK domain) to the kinesin Khc-73 at astral microtubule plus ends, and links transmembrane partners (Fas2, Shaker) to synaptic sites via its PDZ domains. Reason: No informative MF is in GOA beyond bare protein binding and an incorrect GMP kinase activity. Domain-mapping and epistasis show Dlg acts as the adaptor in the Pins-Dlg-Khc-73 complex. This is a molecular function, not a process term. Supporting Evidence: PMID:19766567 We conclude that the PinsLINKER recruits Dlg to the cortex, where the DlgGK domain promotes spindle orientation. PMID:19766567 We conclude that Khc-73 acts downstream of Dlg to promote PinsLINKER/DlgGK-mediated spindle orientation. PMID:16377571 Khc-73 localizes to astral microtubule plus ends, and Dlg/Khc-73 and Dlg/Pins coimmunoprecipitate, suggesting that microtubules induce Pins/Galphai cortical polarity through Dlg/Khc-73 interactions. |
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Download this section (compressed HTML)Q: What is Dlg's molecular activity in basolateral polarity beyond cortically stabilizing Scrib? Does it act through Lgl's aPKC-inhibiting activity or through a separate membrane-binding mechanism?
Q: Should FlyBase's GMP kinase activity TAS rows, and the derived GMP/GDP metabolic process IEA rows, be retired, given that the MAGUK GUK domain is non-catalytic?
Q: Which Dlg isoforms (DlgA vs DlgS97) carry the epithelial versus synaptic functions in vivo, and should isoform-specific annotations be made for the synaptic behaviour phenotypes?
Experiment: Assay purified Dlg GUK domain for GMP phosphotransfer, alongside a GUK point mutant that blocks Pins/GukH binding, to document the absence of catalysis directly for the fly protein.
Experiment: Use endogenously tagged isoform-specific Dlg alleles and proximity labelling in follicle epithelium versus larval muscle to identify the direct partners that carry the polarity and synaptic scaffold functions.
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