{PDOC50945}
{PS50945; I_LWEQ}
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* I/LWEQ domain profile *
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The I/LWEQ  domain is a ~250-residue actin-binding module that is found in the
C-termini of  functionally  diverse proteins from yeast to mammals. The I/LWEQ
domain contains  four  conserved blocks and has been named after the conserved
initial residues  of blocks 1-4. The I/LWEQ domain is generally found near the
C-terminus and   in   association  with  other  domains,  such  as  FERM  (see
<PDOC00566>) or  ENTH  (see  <PDOC50942>). The I/LWEQ domain has been shown to
bind to F-actin and to bundle actin filaments [1-3].

The I/LWEQ domain contains a proteolysis resistant-core that has an all-alpha-
helical structure  composed  of  five  long  down-up-down-up-down antiparallel
helices connected by short loops and one short connecting alpha helix arranged
in a  progressive topology (see <PDB:1R0D>). The proteolysis-resistant core is
followed by   a   C-terminal   latch   region  that  adopts  an  alpha-helical
conformation. The  latch region can mediate oligomerization of I/LWEQ domains,
possibly as  dimers,  and this seems to enhance the F-actin-binding ability of
the proteolysis-resistant core [3].

Some proteins known to contain a I/LWEQ domain are listed below:

 - Animal  talin,  an actin-binding protein involved in integrin-mediated cell
   adhesion and spreading.
 - Slime mold talin homologs TalA and TalB.
 - Animal  Huntingtin-interacting  protein-1  (HIP1),  a  binding  partner  of
   huntingtin, the protein implicated in the etiology of Huntington disease in
   human.
 - Animal  HIP1  related  (HIP1R).  It has a crucial protein-trafficking role,
   mediating associations between actin and chlathrin-coated structures et the
   plasma membrane and trans-Golgi network.
 - Yeast  SLA2  protein.  It  is implicated in polarized assembly of the yeast
   actin cytoskeleton.
 - Slime  mold filopodin, an actin-binding protein that may be involved in the
   control of cell motility and chemotaxis.

The profile we developed covers the entire I/LWEQ domain.

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

-Note: The  I/LWEQ  domain has also been called the talin-HIP1/R/Slap2p actin-
 tethering C-terminal   homology   (THATCH)   domain   (HIP1/R/Slap2p  denotes
 similarity of Slap2p to HIP1 and HIP1R) [3].

-Last update: February 2006 / Profile and text revised.

[ 1] McCann R.O., Craig S.W.
     "The I/LWEQ module: a conserved sequence that signifies F-actin
     binding in functionally diverse proteins from yeast to mammals."
     Proc. Natl. Acad. Sci. U.S.A. 94:5679-5684(1997).
     PubMed=9159132
[ 2] McCann R.O., Craig S.W.
     "Functional genomic analysis reveals the utility of the I/LWEQ module
     as a predictor of protein:actin interaction."
     Biochem. Biophys. Res. Commun. 266:135-140(1999).
     PubMed=10581178; DOI=10.1006/bbrc.1999.1776
[ 3] Brett T.J., Legendre-Guillemin V., McPherson P.S., Fremont D.H.
     "Structural definition of the F-actin-binding THATCH domain from
     HIP1R."
     Nat. Struct. Mol. Biol. 13:121-130(2006).
     PubMed=16415883; DOI=10.1038/nsmb1043

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