Epidermal growth factor receptor kinase substrate 8 (EPS8) is a signalling adapter that possesses actin binding, bundling, and barbed-end capping activities []. It forms a complex with Sos-1, Abi1 and the lipid kinase phosphoinositide 3-kinase (PI3-K) to regulate Rac activation that leads to actin cytoskeletal remodeling []. It is critical for dendritic cell migration []. It is involved in the initial growth of stereocilia in both inner hair cells and outer hair cells []. It also regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF) []. It has been linked to proliferation, metastasis and prognosis of many malignant tumours [].
This entry represents the SH3 domain found in Eps8 and Eps8-like proteins including Eps8-like 1-3. These proteins contain N-terminal phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif []. Epidermal growth factor receptor kinase substrate 8 (EPS8) is a signalling adapter that possesses actin binding, bundling, and barbed-end capping activities []. It forms a complex with Sos-1, Abi1 and the lipid kinase phosphoinositide 3-kinase (PI3-K) to regulate Rac activation that leads to actin cytoskeletal remodeling []. It is critical for dendritic cell migration []. It is involved in the initial growth of stereocilia in both inner hair cells and outer hair cells []. It also regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF) []. It has been linked to proliferation, metastasis and prognosis of many malignant tumours [].
This entry includes EPS8 and EPS8L1-3 from animals.Epidermal growth factor receptor kinase substrate 8 (EPS8) is a signalling adapter that possesses actin binding, bundling, and barbed-end capping activities []. It forms a complex with Sos-1, Abi1 and the lipid kinase phosphoinositide 3-kinase (PI3-K) to regulate Rac activation that leads to actin cytoskeletal remodeling []. It is critical for dendritic cell migration []. It is involved in the initial growth of stereocilia in both inner hair cells and outer hair cells []. It also regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF) []. It has been linked to proliferation, metastasis and prognosis of many malignant tumours [].Similarly to EPS8, EPSLs interact with Abi1 and Sos-1. However, only EPS8L1 and EPS8L2 activate the Rac-GEF activity of Sos-1, and bind to actin in vivo []. Eps8L2 null-mutant mice has been shown to exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology [].
Palladin is a cytoskeletal actin scaffold protein that regulates actin dynamics. The immunoglobulin-like domain of palladin is directly responsible for both actin binding and bundling [, ]. Palladin also interacts with different actin binding proteins and signalling intermediaries required for regulation of cytoskeleton organisation, including profilin [], VASP [], Eps8 [], ezrin [], Lasp-1 [], and Src []. Palladin plays an important role in smooth and skeletal muscle differentiation [, , ], contraction []and cell migration [, , ].Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions []. This entry represents the C-terminal immunoglobulin-like domain (Ig5).
IRSp53, also known as IRS-58 or BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature [].IRSp53 is an adaptor protein that acts at the membrane-actin interface, coupling membrane deformation with F-actin polymerisation []. It is involved in the formation of filopodia and lamellipodia in cultured mesenchymal cells and contributes to assembly/maintenance of tight junctions in cultured epithelial cells []. IRSp53 contains an N-terminal I-BAR domain, followed by a partial CRIB domain and a SH3 domain. It binds to small GTPase Cdc42, Rac1 and WAVE1 []. IRSp53 binds Rac through its I-BAR domain and to WAVE through its SH3 domain, and thus contributes to membrane ruffling []. Its SH3 domain also interacts with other regulators of actin dynamics, such as WAVE2, Mena, mDia1, Dynamin1, Eps8 and N-WASP [].
This entry represents the SH3 domain of IRSp53. The SH3 domain of IRSp53 has been shown to bind the proline-rich C terminus of EspFu (E. coli secreted protein F-like from prophage U) [].IRSp53, also known as IRS-58 or BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature [].IRSp53 is an adaptor protein that acts at the membrane-actin interface, coupling membrane deformation with F-actin polymerisation []. It is involved in the formation of filopodia and lamellipodia in cultured mesenchymal cells and contributes to assembly/maintenance of tight junctions in cultured epithelial cells []. IRSp53 contains an N-terminal I-BAR domain, followed by a partial CRIB domain and a SH3 domain. It binds to small GTPase Cdc42, Rac1 and WAVE1 []. IRSp53 binds Rac through its I-BAR domain and to WAVE through its SH3 domain, and thus contributes to membrane ruffling []. Its SH3 domain also interacts with other regulators of actin dynamics, such as WAVE2, Mena, mDia1, Dynamin1, Eps8 and N-WASP [].
