description
WASP and WAVE proteins belong to the Wiskott-Aldrich Syndrome protein family, with recessive mutations in the founding member WASP being responsible for the X-linked recessive immunodeficieny known as the Wiskott-Aldrich Syndrome. WASP proteins include WASP and WASL (N-WASP). WAVE proteins include WASF1 (WAVE1), WASF2 (WAVE2) and WASF3 (WAVE3). WASPs and WAVEs contain a VCA domain (consisting of WH2 and CA subdomains) at the C-terminus, responsible for binding to G-actin (WH2 subdomain) and the actin-associated ARP2/3 complex (CA subdomain). WASPs contain a WH1 (WASP homology 1) domain at the N-terminus, responsible for binding to WIPs (WASP-interacting proteins). A RHO GTPase binding domain (GBD) is located in the N-terminal half of WASPs and C-terminally located in WAVEs. RHO GTPases activate WASPs by disrupting the autoinhibitory interaction between the GBD and VCA domains, which allows WASPs to bind actin and the ARP2/3 complex and act as nucleation promoting factors in actin polymerization. WAVEs have the WAVE/SCAR homology domain (WHD/SHD) at the N-terminus, which binds ABI, NCKAP1, CYFIP2 and BRK1 to form the WAVE regulatory complex (WRC). Binding of the RAC1:GTP to the GBD of WAVEs most likely induces a conformational change in the WRC that allows activating phosphorylation of WAVEs by ABL1, thus enabling them to function as nucleation promoting factors in actin polymerization through binding G-actin and the ARP2/3 complex (Reviewed by Lane et al. 2014)

external resources
NCBI:1269518
REACTOME:R-HSA-5663213
PUBMED:24969695

genes
ABL1 , ACTB , ACTG1 , BTK , CDC42 , GRB2 , NCKAP1L , NCK1 , MAPK1 , MAPK3 , PTK2 , RAC1 , WAS , WIPF1 , WASF1 , WASL , ABI1 , ARPC5 , ARPC4 , ARPC3 , ARPC1B , ACTR3 , ACTR2 , ARPC2 , ABI2 , WASF2 , BAIAP2 , ARPC1A , NCKAP1 , WASF3 , CYFIP1 , CYFIP2 , NCKIPSD , BRK1 , WIPF2 , WIPF3 ,