first tandem Wiskott Aldrich syndrome homology region 2 (WH2 motif) repeat found in human Neural Wiskott-Aldrich syndrome protein (N-WASP) and related domains
This subfamily includes the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in human Neural Wiskott-Aldrich syndrome protein (N-WASP or Neural WASP) and related domains. N-WASP integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the actin related protein (Arp)2/3 complex. It interacts with actin via the WH2 domain. N-WASP plays an important role in the deactivation or attenuation of B cell receptor signaling. N-WASP regulates filopodia formation and membrane invagination, as compared to WAVE proteins that serve as Rac1 effectors in the formation of lamellipodia. Filopodia are thin, actin-rich surface projections that are extended and maintained by N-WASP together with CDC42. N-WASP also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization. It binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. It also plays a role in dendrite spine morphogenesis. Unphosphorylated N-WASP is preferentially localized in the nucleus and in the cytoplasm when phosphorylated; it is exported from the nucleus by a nuclear export signal (NES)-dependent mechanism to the cytoplasm.
Jiyao W et al.(2023). "The conserved domain database in 2023.",