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Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome Protein Family Member 3 (WASP-3 or WAVE3) This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in the Wiskott-Aldrich syndrome protein (WASP) relative WAVE 3 (also called WASP-family verprolin homologous protein 3 or WASF3 or SCAR3 or WAVE3). WAVE3 is a downstream effector protein involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. It plays a role in the regulation of cell morphology and cytoskeletal organization and is required in the control of cell shape. It forms a hetero-pentameric WAVE regulatory complex (WRC) with additional proteins in the cell (Sra1/Cyfip1, Nap1/Hem-2, Abi and HSPC300) that regulates actin filament reorganization via its interaction with the actin related protein (Arp)2/3 complex. The WRC is stimulated by the Rac GTPase, kinases and phosphatidylinositols, and binds and activates the Arp2/3 complex via WAVE3 C-terminal domain. It interacts with actin via the WH2 domain. This actin polymerization process is also involved in cancer cell invasion and metastasis. WASF3 has been shown to have a central role in cancer cell invasion and metastasis; elevated WAVE3 expression promotes metastasis in breast cancer and inactivation of WAVE3 in highly metastatic breast cancer cells has been shown to suppress invasion and metastasis. WAVE3 may also be pivotal in ovarian cancer cell motility, invasion and oncogenesis. In gastric cancer patients, WAVE3 expression correlates with poor outcome. In pancreatic cancer tissues, expression is prominently higher that in normal tissues and may be associated with lymphatic metastasis and poorly differentiated tumors; findings suggest that WAVE3 influences cell proliferation, migration and invasion via the AKT pathway. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",