D
IPR035462

Eps8, SH3 domain

InterPro entry
Short nameEps8_SH3
Overlapping
homologous
superfamilies
 
domain relationships

Description

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
[1]
.

Epidermal growth factor receptor kinase substrate 8 (EPS8) is a signalling adapter that possesses actin binding, bundling, and barbed-end capping activities
[5]
. 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
[6]
. It is critical for dendritic cell migration
[5]
. It is involved in the initial growth of stereocilia in both inner hair cells and outer hair cells
[3]
. It also regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF)
[4]
. It has been linked to proliferation, metastasis and prognosis of many malignant tumours
[2]
.

References

1.SH3 domain ligand binding: What's the consensus and where's the specificity? Saksela K, Permi P. FEBS Lett. 586, 2609-14, (2012). View articlePMID: 22710157

2.[Correlation of Eps8 with proliferation, metastasis and prognosis of malignant tumors]. Sun J, Jin LY, Wang HY, Zhou JQ, Li YJ, He YZ, Li YH. Zhongguo Shi Yan Xue Ye Xue Za Zhi 21, 493-7, (2013). View articlePMID: 23628062

3.The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of Mammalian cochlear outer hair cells. Olt J, Mburu P, Johnson SL, Parker A, Kuhn S, Bowl M, Marcotti W, Brown SD. PLoS ONE 9, e87331, (2014). View articlePMID: 24475274

4.Eps8 regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF). Menna E, Disanza A, Cagnoli C, Schenk U, Gelsomino G, Frittoli E, Hertzog M, Offenhauser N, Sawallisch C, Kreienkamp HJ, Gertler FB, Di Fiore PP, Scita G, Matteoli M. PLoS Biol. 7, e1000138, (2009). View articlePMID: 19564905

5.The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration. Frittoli E, Matteoli G, Palamidessi A, Mazzini E, Maddaluno L, Disanza A, Yang C, Svitkina T, Rescigno M, Scita G. Immunity 35, 388-99, (2011). View articlePMID: 21835647

6.The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway. Offenhauser N, Borgonovo A, Disanza A, Romano P, Ponzanelli I, Iannolo G, Di Fiore PP, Scita G. Mol. Biol. Cell 15, 91-8, (2004). View articlePMID: 14565974

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