Nck SH3 domain 1 (Nck SH3.1)

The **Nck SH3 domain 1** (Nck SH3.1) is the first Src homology 3 domain in the Nck adapter proteins (Nck1 and Nck2), which are composed of one SH2 and three SH3 domains[1][3][6]. The SH3.1 domain specifically binds to proline-rich motifs, notably the PxxDY sequence present in signaling proteins such as the CD3ε chain of the T cell receptor (TCR), and mediates the assembly of signaling complexes crucial for cytoskeletal remodeling and receptor-initiated signaling cascades[1][6]. This binding regulates downstream signaling pathways involved in cell migration, immune synapse formation, and cytoskeletal reorganization[1][3][4][6]. In cancer and immune-related diseases, dysregulation of Nck SH3.1 interactions can lead to altered cell movement and proliferation. While not currently a direct therapeutic drug target, Nck SH3.1 is a validated node for small-molecule or peptide inhibitors aiming to disrupt pathological protein–protein interactions[2].

Other names

Nck1 SH3 domain 1Nck2 SH3 domain 1SH3 domain of Nck1SH3.1 domain of Nck1/Nck2

Inhibition or modulation of protein–protein interaction between Nck SH3.1 and its proline-rich ligands