PROSITE documentation PDOC50814 [for PROSITE entry PS50814]

WIF domain profile

The WIF domain is an around 140-amino acid module which presents an independent folding unit in receptor molecules that bind to palmitoylated signaling proteins. It has been identified in the extracellular region of the Ryk receptor tyrosine kinases and in the secreted Wnt-inhibitory-factor-1 (WIF-1) proteins. As the WIF module is both necessary and sufficient for Wnt binding by WIF-1, it has been proposed that the WIF module of Ryk receptors might also serve to bind to Wnt proteins or related ligands. It has been suggested that the WIF domain recognizes and binds to Wnts that have been activated by palmitoylation. The WIF modules found in Ryk receptor tyrosine kinases and WIF-1 proteins contain conserved sequence motifs, including two conserved cysteines which form a disulfide bridge [1,2].

The fold of the WIF domain is related to the immunoglobulin fold (see <PDOC50835>). It comprises nine β-strands and two α-helices, with two of the β-strands (6 and 9) interrupted by four and six residues of irregular secondary structure, respectively (see <PDB:2D3J>). The N and C termini are located at opposite ends of the domain, in agreement with its function as a structurally independent module in different sequence contexts [2].

Some proteins known to contain a WIF module are listed below:

• Mammalian Ryk proteins. Although mammalian Ryk proteins are found in most tissues, little is known about their function. They are believed to be involved in cellular recognition processes.
• Caenorhabditis elegans lin-18, the Ryk homolog. It is required for cell- cuticle recognition.
• Drosophila melanogaster derailed (drl) and doughnut (dnt) proteins. The drl protein plays a crucial role in cell-recognition processes controlling nervous system development and muscle development. The dnt receptor has a related and significantly overlapping biochemical function.
• Animal WIF-1 proteins. WIF-1s are secreted proteins, consisting of an N- terminal WIF domain and five EGF-like repeats (see <PDOC00021>). They bind to wnt proteins and inhibit their activities.

The profile we developed covers the entire WIF domain.