{PDOC50229}
{PS50229; WH1}
{BEGIN}
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* WH1 domain profile *
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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 [1-5].

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  beta-sheets  (B1-B7)  that  form  a beta-sandwich, capped by a
C-terminal   alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: March 2005 / First entry.

[ 1] Prehoda K.E., Lee D.J., Lim W.A.
     "Structure of the enabled/VASP homology 1 domain-peptide complex: a
     key component in the spatial control of actin assembly."
     Cell 97:471-480(1999).
     PubMed=10338211
[ 2] Zettl M., Way M.
     "The WH1 and EVH1 domains of WASP and Ena/VASP family members bind
     distinct sequence motifs."
     Curr. Biol. 12:1617-1622(2002).
     PubMed=12372256
[ 3] Callebaut I.
     "An EVH1/WH1 domain as a key actor in TGFbeta signalling."
     FEBS Lett. 519:178-180(2002).
     PubMed=12023040
[ 4] Krause M., Dent E.W., Bear J.E., Loureiro J.J., Gertler F.B.
     "Ena/VASP proteins: regulators of the actin cytoskeleton and cell
     migration."
     Annu. Rev. Cell Dev. Biol. 19:541-564(2003).
     PubMed=14570581; DOI=10.1146/annurev.cellbio.19.050103.103356
[ 5] Harmer N.J., Sivak J.M., Amaya E., Blundell T.L.
     "1.15 A crystal structure of the X. tropicalis Spred1 EVH1 domain
     suggests a fourth distinct peptide-binding mechanism within the EVH1
     family."
     FEBS Lett. 579:1161-1166(2005).
     PubMed=15710406; DOI=10.1016/j.febslet.2004.11.114

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