SCAR (WAVE) is the single Drosophila member of the SCAR/WAVE subfamily of WASP-family nucleation-promoting factors. Its C-terminal VCA region binds actin monomers and the Arp2/3 complex and stimulates nucleation of branched actin filament networks. SCAR is held inactive within the five-subunit WAVE regulatory complex (with Cyfip/Sra-1, Hem/Kette, Abi and HSPC300), which stabilises it against proteasomal degradation and couples its activation to Rac signalling and to membrane receptors carrying WIRS motifs. SCAR drives lamellipodia and other cortical protrusions in cultured cells, macrophages and epithelia, and is required for myoblast fusion, axon growth and guidance, neuronal migration, egg chamber development and integrity of integrin junctions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001764 neuron migration | IMP PMID:21726548 The Hem protein mediates neuronal migration by inhibiting WA... | KEEP AS NON CORE | Summary: SCAR is required for migration of the RP2 neuron. Reason: IMP: Hem and WAVE mutants mis-migrate GMC-1/RP2; Hem acts by stabilising WAVE. Developmental/tissue-level phenotype that reflects the general requirement for WRC-driven, Arp2/3-dependent actin assembly; retained as non-core. Supporting Evidence: PMID:21726548 Here, we show that the Hem protein, via the WAVE complex, regulates migration of GMC-1 and its progeny RP2 neuron. |
| GO:0003779 actin binding | IEA GO_REF:0000120 | MODIFY | Summary: SCAR binds actin through its WH2-containing VCA region. Reason: Correct but general: the SCAR/WAVE C-terminal VCA region binds actin monomers via its WH2 (verprolin homology) domain and the Arp2/3 complex. The more specific term is actin monomer binding. Proposed replacements: actin monomer binding Supporting Evidence: file:DROME/SCAR/SCAR-uniprot.txt Binds actin and the Arp2/3 complex. |
| GO:0005515 protein binding | IPI PMID:23424199 The F-BAR protein Cip4/Toca-1 antagonizes the formin Diaphan... | REMOVE | Summary: Generic protein binding. Reason: Generic protein binding: SCAR is pulled down by GST-Cip4. No informative binding term is established by this pulldown alone. |
| GO:0005634 nucleus | IDA PMID:22275148 Developmental expression of Drosophila Wiskott-Aldrich Syndr... | KEEP AS NON CORE | Summary: SCAR is transiently detected in the nucleus during mitosis. Reason: Antibody staining shows WASP-family proteins, including SCAR, entering the nucleus during mitosis. The functional significance is unknown; non-core. Supporting Evidence: PMID:22275148 Drosophila Wash, WASp, SCAR and Whamy exhibit dynamic subcellular localization changes during mitosis, including localization within the nucleus |
| GO:0005737 cytoplasm | IDA PMID:22275148 Developmental expression of Drosophila Wiskott-Aldrich Syndr... | MODIFY | Summary: SCAR is cytoplasmic. Reason: Correct but general. SCAR functions in the cytoplasm as a subunit of the WAVE regulatory complex, and the gene already carries the more specific cytoplasmic term GO:0031209 SCAR complex (a descendant of cytoplasm). Proposed replacements: SCAR complex Supporting Evidence: PMID:22275148 SCAR is expressed uniformly in the cytoplasm of all cells throughout embryogenesis |
| GO:0005856 cytoskeleton | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: WRC subunit predicted to be cytoskeleton-associated. Reason: UniProt subcellular-location mapping. The WRC is a cytoplasmic complex recruited to the membrane at protrusion tips, where it acts on the actin network; 'cytoskeleton' is a loose but acceptable association. No more specific cytoskeletal location is established for SCAR; non-core. Supporting Evidence: file:DROME/SCAR/SCAR-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0007015 actin filament organization | IMP PMID:24183239 Drosophila pupal macrophages--a versatile tool for combined ... | ACCEPT | Summary: SCAR is required for lamellipodial actin networks in macrophages. Reason: IMP in pupal macrophages; SCAR knockdown disrupts lamellipodial actin. Actin filament organization is the level of the phenotype reported; SCAR's molecular role is captured by GO:0034314. Supporting Evidence: PMID:24183239 We knocked down components regulating lamellipodia formation, including WAVE |
| GO:0007520 myoblast fusion | IGI PMID:18388318 WASP and SCAR have distinct roles in activating the Arp2/3 c... | KEEP AS NON CORE | Summary: SCAR is required for myoblast fusion. Reason: WRC/SCAR-driven Arp2/3 actin polymerisation forms the F-actin focus in fusion-competent myoblasts. A major in vivo requirement, but a developmental use of the core actin-nucleation function; non-core. Supporting Evidence: PMID:18388318 the F-actin regulator scar also controls F-actin formation during myoblast fusion |
| GO:0007520 myoblast fusion | IGI PMID:18388318 WASP and SCAR have distinct roles in activating the Arp2/3 c... | KEEP AS NON CORE | Summary: SCAR is required for myoblast fusion. Reason: WRC/SCAR-driven Arp2/3 actin polymerisation forms the F-actin focus in fusion-competent myoblasts. A major in vivo requirement, but a developmental use of the core actin-nucleation function; non-core. Supporting Evidence: PMID:18388318 the F-actin regulator scar also controls F-actin formation during myoblast fusion |
| GO:0007520 myoblast fusion | IMP PMID:18003739 SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling... | KEEP AS NON CORE | Summary: SCAR is required for myoblast fusion. Reason: WRC/SCAR-driven Arp2/3 actin polymerisation forms the F-actin focus in fusion-competent myoblasts. A major in vivo requirement, but a developmental use of the core actin-nucleation function; non-core. Supporting Evidence: PMID:18003739 Mutants in SCAR and Arp2/3 have a fusion block and foci phenotype |
| GO:0007520 myoblast fusion | IMP PMID:18388318 WASP and SCAR have distinct roles in activating the Arp2/3 c... | KEEP AS NON CORE | Summary: SCAR is required for myoblast fusion. Reason: WRC/SCAR-driven Arp2/3 actin polymerisation forms the F-actin focus in fusion-competent myoblasts. A major in vivo requirement, but a developmental use of the core actin-nucleation function; non-core. Supporting Evidence: PMID:18388318 the F-actin regulator scar also controls F-actin formation during myoblast fusion |
| GO:0007520 myoblast fusion | IMP PMID:21098115 An invasive podosome-like structure promotes fusion pore for... | KEEP AS NON CORE | Summary: SCAR is required for myoblast fusion. Reason: WRC/SCAR-driven Arp2/3 actin polymerisation forms the F-actin focus in fusion-competent myoblasts. A major in vivo requirement, but a developmental use of the core actin-nucleation function; non-core. Supporting Evidence: PMID:21098115 Two actin nucleation-promoting factors of the Arp2/3 complex, WASP and Scar, are required for the formation of the F-actin foci |
| GO:0010592 positive regulation of lamellipodium assembly | IMP PMID:20197404 Polarity proteins and Rho GTPases cooperate to spatially org... | ACCEPT | Summary: SCAR/WRC promotes lamellipodia in epithelial cells. Reason: IMP: downstream of Rac, SCAR and Arp2/3 complexes generate lamellipodia in epithelial cells. Core process for the WRC. Supporting Evidence: PMID:20197404 Sif/TIAM1, Rac, SCAR and Arp2/3 complexes catalyse actin nucleation to generate lamellipodia and filopodia |
| GO:0030029 actin filament-based process | TAS PMID:15196561 The WASP-Arp2/3 pathway: genetic insights. | MODIFY | Summary: SCAR in the WASP-Arp2/3 pathway (review). Reason: TAS from a review of WASP/SCAR-Arp2/3 genetics. Correct but very general; the gene already carries the specific term GO:0034314 Arp2/3 complex-mediated actin nucleation. Proposed replacements: Arp2/3 complex-mediated actin nucleation Supporting Evidence: PMID:15196561 Recent studies suggest that Scar is a more important regulator of Arp2/3 activity in actin-dependent morphological processes than WASP |
| GO:0030036 actin cytoskeleton organization | IEA GO_REF:0000120 | MODIFY | Summary: SCAR family predicted to organise actin. Reason: InterPro/UniRule mapping. Correct but general; SCAR already carries the specific term GO:0034314 Arp2/3 complex-mediated actin nucleation. Proposed replacements: Arp2/3 complex-mediated actin nucleation Supporting Evidence: file:DROME/SCAR/SCAR-uniprot.txt Promotes formation of actin filaments. |
| GO:0030036 actin cytoskeleton organization | IMP PMID:18003739 SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling... | ACCEPT | Summary: SCAR is required for actin cytoskeleton organization in vivo. Reason: IMP: loss of function disrupts F-actin organization (e.g. actin foci at myoblast fusion sites, neuronal or bristle actin). Actin cytoskeleton organization is the level of the reported phenotype. Supporting Evidence: PMID:18003739 Mutants in SCAR and Arp2/3 have a fusion block and foci phenotype |
| GO:0030866 cortical actin cytoskeleton organization | IMP PMID:14588242 Abi, Sra1, and Kette control the stability and localization ... | ACCEPT | Summary: SCAR is required for SCAR-dependent cortical actin protrusions. Reason: RNAi in Drosophila cells shows that Abi, Sra1/Cyfip and Kette/Hem stabilise and localise SCAR and are required, like SCAR itself, for Arp2/3-dependent cortical protrusions (lamellipodia). Core process of the WRC. Supporting Evidence: PMID:14588242 Abi and two components of a recently identified SCAR complex, Sra1 (p140/PIR121/CYFIP) and Kette (Nap1/Hem), protect SCAR from proteasome-mediated degradation and are critical for SCAR localization and for the generation of Arp2/3-dependent protrusions |
| GO:0031209 SCAR complex | IDA PMID:24439376 The WAVE regulatory complex links diverse receptors to the a... | ACCEPT | Summary: SCAR is a subunit of the WAVE regulatory (SCAR) complex. Reason: SCAR is one of the five subunits of the WAVE regulatory complex (SCAR, Abi, Hem/Kette, Cyfip/Sra-1, HSPC300); purified Drosophila WRC and in vivo co-fractionation confirm membership. Core location. Supporting Evidence: PMID:24439376 Indeed, purified Drosophila WRC (2MBP-dWRC) also bound to the wild type human PCDH10 CT but not the mutant with a disrupted WIRS |
| GO:0031209 SCAR complex | IPI PMID:21900504 Membrane-targeted WAVE mediates photoreceptor axon targeting... | ACCEPT | Summary: SCAR is a subunit of the WAVE regulatory (SCAR) complex. Reason: SCAR is one of the five subunits of the WAVE regulatory complex (SCAR, Abi, Hem/Kette, Cyfip/Sra-1, HSPC300); purified Drosophila WRC and in vivo co-fractionation confirm membership. Core location. Supporting Evidence: PMID:21900504 In abi mutants, WAVE is unstable but restored by reexpression of Abi, confirming that Abi controls the integrity of the WAVE complex in vivo. |
| GO:0033627 cell adhesion mediated by integrin | IMP PMID:20937809 WAVE forms hetero- and homo-oligomeric complexes at integrin... | KEEP AS NON CORE | Summary: cell adhesion mediated by integrin requires SCAR. Reason: Experimental phenotype supporting this process. Developmental/tissue-level phenotype that reflects the general requirement for WRC-driven, Arp2/3-dependent actin assembly; retained as non-core. Supporting Evidence: PMID:20937809 hetero- and homooligomeric WAVE complexes co-localize with Integrin and Talin suggesting a role in integrin-mediated cell adhesion |
| GO:0034314 Arp2/3 complex-mediated actin nucleation | IDA PMID:19633175 Wash functions downstream of Rho and links linear and branch... | ACCEPT | Summary: SCAR is an Arp2/3-activating nucleation-promoting factor. Reason: SCAR/WAVE is a WASP-family Arp2/3 activator whose VCA region delivers actin monomers to the Arp2/3 complex to nucleate branched filaments. Core process. Supporting Evidence: PMID:19633175 Wiskott-Aldrich Syndrome (WAS) family proteins are Arp2/3 activators that mediate the branched-actin network formation required for cytoskeletal remodeling, intracellular transport and cell locomotion. file:DROME/SCAR/SCAR-uniprot.txt Binds actin and the Arp2/3 complex. |
| GO:0045177 apical part of cell | IDA PMID:20937809 WAVE forms hetero- and homo-oligomeric complexes at integrin... | KEEP AS NON CORE | Summary: SCAR is enriched at a polarized cortical domain of epithelial cells. Reason: Context-specific localization in epithelia (basal cell compartments/tricellular contacts of wing or follicle epithelium; apical rhabdomere region in eye). As precise as warranted; peripheral to the core WRC location. Supporting Evidence: PMID:20937809 Detailed localization analyses show that formation of WAVE complexes specifically takes place at basal cell compartments promoting actin polymerization. |
| GO:0045178 basal part of cell | IDA PMID:20937809 WAVE forms hetero- and homo-oligomeric complexes at integrin... | KEEP AS NON CORE | Summary: SCAR is enriched at a polarized cortical domain of epithelial cells. Reason: Context-specific localization in epithelia (basal cell compartments/tricellular contacts of wing or follicle epithelium; apical rhabdomere region in eye). As precise as warranted; peripheral to the core WRC location. Supporting Evidence: PMID:20937809 Detailed localization analyses show that formation of WAVE complexes specifically takes place at basal cell compartments promoting actin polymerization. |
| GO:0048846 axon extension involved in axon guidance | IMP PMID:21900504 Membrane-targeted WAVE mediates photoreceptor axon targeting... | KEEP AS NON CORE | Summary: axon extension involved in axon guidance requires SCAR. Reason: Experimental phenotype supporting this process. Developmental/tissue-level phenotype that reflects the general requirement for WRC-driven, Arp2/3-dependent actin assembly; retained as non-core. Supporting Evidence: PMID:21900504 Abi exerts nonautonomous control of photoreceptor axon targeting in the Drosophila visual system through WAVE |
| GO:0051125 regulation of actin nucleation | IMP PMID:21900504 Membrane-targeted WAVE mediates photoreceptor axon targeting... | MODIFY | Summary: SCAR promotes actin nucleation. Reason: Correct but general: the nucleation SCAR promotes is specifically Arp2/3 complex-mediated. Replace with the precise term. Proposed replacements: positive regulation of Arp2/3 complex-mediated actin nucleation Supporting Evidence: PMID:21900504 Furthermore, we show that the rescue ability of membrane-recruited WAVE is due to an activation of Arp2/3 in the absence of Abi. |
| GO:0051127 positive regulation of actin nucleation | IMP PMID:20937809 WAVE forms hetero- and homo-oligomeric complexes at integrin... | MODIFY | Summary: SCAR promotes actin nucleation. Reason: Correct but general: the nucleation SCAR promotes is specifically Arp2/3 complex-mediated. Replace with the precise term. Proposed replacements: positive regulation of Arp2/3 complex-mediated actin nucleation Supporting Evidence: PMID:20937809 WAVE-dependent Arp2/3-mediated actin nucleation is important for the maintenance of stable integrin junctions |
| GO:0051489 regulation of filopodium assembly | IMP PMID:24183239 Drosophila pupal macrophages--a versatile tool for combined ... | KEEP AS NON CORE | Summary: WRC influences filopodial protrusions. Reason: Context-dependent effects of WRC loss on filopodia (epithelial basal filopodia; follicle-cell protrusions). Filopodia arise downstream of the branched network; peripheral to the core lamellipodial function. Supporting Evidence: PMID:24183239 We knocked down components regulating lamellipodia formation, including WAVE |
| GO:0051491 positive regulation of filopodium assembly | IMP PMID:20197404 Polarity proteins and Rho GTPases cooperate to spatially org... | KEEP AS NON CORE | Summary: WRC influences filopodial protrusions. Reason: Context-dependent effects of WRC loss on filopodia (epithelial basal filopodia; follicle-cell protrusions). Filopodia arise downstream of the branched network; peripheral to the core lamellipodial function. Supporting Evidence: PMID:20197404 Sif/TIAM1, Rac, SCAR and Arp2/3 complexes catalyse actin nucleation to generate lamellipodia and filopodia |
| GO:0071933 Arp2/3 complex binding | ISS file:DROME/SCAR/SCAR-uniprot.txt | NEW | Summary: SCAR binds the Arp2/3 complex through its C-terminal VCA region. Reason: SCAR/WAVE-family nucleation-promoting factors activate the Arp2/3 complex by binding it through the central-acidic part of the VCA region; the UniProt rule-based annotation for Drosophila SCAR states this binding, and the fly WRC is a characterised Arp2/3 activator (SCAR is annotated to GO:0034314 Arp2/3 complex-mediated actin nucleation by IDA). No GOA row currently captures this core molecular function. Supporting Evidence: file:DROME/SCAR/SCAR-uniprot.txt Binds actin and the Arp2/3 complex. PMID:19633175 Wiskott-Aldrich Syndrome (WAS) family proteins are Arp2/3 activators that mediate the branched-actin network formation required for cytoskeletal remodeling, intracellular transport and cell locomotion. |
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Download this section (compressed HTML)SCAR (SCAR) encodes a primary regulator of the Arp2/3 complex, which promotes actin polymerization and influences cell shape and motility. It is involved in myoblast fusion, eye morphogenesis and axogenesis.
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