PROSITE documentation PDOC50229

WH1 domain profile

The WH1 (WASP-Homology 1, or Wiskott-Aldrich homology 1) or EVH1 (Ena/VASP homology 1, or Enabled/Vasodilator-stimulated phosphoprotein homology 1) domain is an ~110 amino acids protein-protein interaction module. WH1 proteins occur in eukaryotes from yeast to mammals and play a role in signaling and regulation of the cytoskeleton. The WH1 domain is usually located in the N-terminal part. A CRIB domain (see <PDOC50108>) or a WH2 domain (see <PDOC51082>) can occur C-terminal to the WH1 domain. Most WH1 domains bind proline-rich sequences: the WASP and the Enabled/VASP families bind to LPPPEP and to FPPPP peptides, respectively, while the Homer/Vesl family binds to PPXXF motifs, and less proline-rich peptides could be ligands as well [1,2,3,4,5].

Tertiary structures of the WH1 domains from different proteins show structure similarities with the pleckstrin homology (PH) domain (see <PDOC50003>) and with the WH1-related Ran binding domain (see <PDOC50196>). The WH1 domain comprises two β-sheets (B1-B7) that form a β-sandwich, capped by a C-terminal α-helix (see <PDB:1XOD>). The principal peptide binding activity is formed by a groove between the strands B1, B2, B6 and B7. Proteins which can bind to WH1 domains are e.g. Zyxin, Vinculin, WASP interacting protein (WIP), metabotropic glutamate receptors and the Listeria monocytogenes ActA protein [4,5].

Some proteins known to contain a WH1 domain:

• Mammalian vasodilator-stimulated phosphoprotein (VASP), an actin- and profilin-binding microfilament-associated protein. May act in concert with profilin to convey signal transduction to actin filament production.
• Mammalian Wiskott-Aldrich syndrome protein (WASP), a possible regulator of lymphocyte and platelet function. Defects in WASP are the cause of Wiskott- Aldrich syndrome (WAS), an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea.
• Mammalian enable protein (Mena), an adapter protein implicated in the spatial control of actin assembly.
• Mammalian homer/vesl proteins, postsynaptic density scaffolding proteins. Homer protein binds to metabotropic glutamate receptors and inositol trisphosphate receptors, involved in intracellular calcium signaling in neurons.
• Metazoan Sprouty-related, EVH1 domain containing (Spred)1-3 proteins, Ras-dependent inhibitors of extracellular signal-regulated kinase signaling, induced by various growth factors.
• Fruit fly still life protein type 1 (SIF1) protein, which interacts with Rho-like GTPases and participates in the organization of actin cytoskeleton.

The profile we developed covers the entire WH1 domain.