PROSITE documentation PDOC50945I/LWEQ domain profile
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.
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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | McCann R.O. Craig S.W. |
| Title | The I/LWEQ module: a conserved sequence that signifies F-actin binding in functionally diverse proteins from yeast to mammals. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 94:5679-5684(1997). | |
| PubMed ID | 9159132 |
| 2 | Authors | McCann R.O. Craig S.W. |
| Title | Functional genomic analysis reveals the utility of the I/LWEQ module as a predictor of protein:actin interaction. | |
| Source | Biochem. Biophys. Res. Commun. 266:135-140(1999). | |
| PubMed ID | 10581178 | |
| DOI | 10.1006/bbrc.1999.1776 |
| 3 | Authors | Brett T.J. Legendre-Guillemin V. McPherson P.S. Fremont D.H. |
| Title | Structural definition of the F-actin-binding THATCH domain from HIP1R. | |
| Source | Nat. Struct. Mol. Biol. 13:121-130(2006). | |
| PubMed ID | 16415883 | |
| DOI | 10.1038/nsmb1043 |
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