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Group:MUZIC:Mena VASP
From Proteopedia

Mena/VASP
Introduction'Ena/VASP protein family contributes cell motility and cell adhesion through the regulation of actin dynamics and consists of three members in mammalian: Vasodilator-stimulated phosphoprotein (VASP), Mena (mammalian enabled), and the Ena-VASP-like protein Evl. They contain three domains: N-terminal Ena/Vasp like homology domain 1 (EVH1) with an optimal core consensus motif of “FPPPP”, central proline-rich region and C-terminal EVH2 domain. Ena/VASP proteins associate with actin filaments and localize in the hot spots of actin reassembly such as tips of lamellipodia and filopodia.
Sequence annotationEna/VASP protein differs in size of proline-rich region and Mena contains a 91-residue region between the EVH1 domain and proline-rich core with 13 repeats of a 5-residue “LERER" motif [1]. VASP uniprot Mena (Protein enabled homolog) uniprot Evl uniprot Structure1egx NMR Structure of EVH1 domain of human VASP 1usd 1use Crystal structure of C-terminal coil -coiled part of EVH2 domain of human VASP 1evh Crystal structure of EVH1 domain of Mena (Mus Musculus) in complex with FPPP peptide
Function and interactionEVH1 domain of Mena/VASP binds to the cytoskeleton proteins containing FPPPP motif, such as vinculin [2], lamellipodin [3], zyxin [4], palladin [5] and Xin [6]. The Pro-rich region of Mena/VASP binds profilin and the SH3 and WW domains of various signaling and scaffolding proteins. EVH2 domain comprises F- ang G-Actin binding sites and C-terminal coiled coil region, also known as tetramerization domain [7]. It was shown recently that Mena binds with fibronectin receptor α5β1 integrin via “LERER" motif [8]. It is suggested that Mena/VASP bind to the barbed end of actin filaments and prevent their capping by CapZ [9]. Regulation of VASP protein activity occurs through phosphorylation at Ser-157, Ser-239, and Thr-278.
PathologyIt was shown that delocalization of Mena/VASP proteins from intercalated discs at the interface of myocytes cause the severe cardiomyopathy [10] References
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