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	PROSITE documentation PDOC50229

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.

Last update:

March 2005 / First entry.

PROSITE method (with tools and information) covered by this documentation:

WH1, PS50229; WH1 domain profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 57
  • detected by PS50229: 45 (true positives)
  • undetected by PS50229: 12 (12 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50229:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS50229
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50229
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50229
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50229
• View ligand binding statistics of PS50229
• Matching PDB structures: 1DDV 1DDW 1EGX 1EVH ... [ALL]

1	Authors	Prehoda K.E., Lee D.J., Lim W.A.
	Title	Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly.
	Source	Cell 97:471-480(1999).
	PubMed ID	10338211

2	Authors	Zettl M., Way M.
	Title	The WH1 and EVH1 domains of WASP and Ena/VASP family members bind distinct sequence motifs.
	Source	Curr. Biol. 12:1617-1622(2002).
	PubMed ID	12372256

3	Authors	Callebaut I.
	Title	An EVH1/WH1 domain as a key actor in TGFbeta signalling.
	Source	FEBS Lett. 519:178-180(2002).
	PubMed ID	12023040

4	Authors	Krause M., Dent E.W., Bear J.E., Loureiro J.J., Gertler F.B.
	Title	Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration.
	Source	Annu. Rev. Cell Dev. Biol. 19:541-564(2003).
	PubMed ID	14570581
	DOI	10.1146/annurev.cellbio.19.050103.103356

5	Authors	Harmer N.J., Sivak J.M., Amaya E., Blundell T.L.
	Title	1.15 A crystal structure of the X. tropicalis Spred1 EVH1 domain suggests a fourth distinct peptide-binding mechanism within the EVH1 family.
	Source	FEBS Lett. 579:1161-1166(2005).
	PubMed ID	15710406
	DOI	10.1016/j.febslet.2004.11.114

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