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 [1,2,3].

The I/LWEQ domain contains a proteolysis resistant-core that has an all-α-helical structure composed of five long down-up-down-up-down antiparallel helices connected by short loops and one short connecting α helix arranged in a progressive topology (see <PDB:1R0D>). The proteolysis-resistant core is followed by a C-terminal latch region that adopts an α-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.