Occurs as extracellular domain in metazoan Ryk receptor tyrosine kinases. C. elegans Ryk is required for cell-cuticle recognition. WIF-1 binds to Wnt and inhibits its activity.
This entry represents the WIF domain, it is found in the RYK tyrosine kinase receptors and WIF the Wnt-inhibitory-factor. The domain is extracellular and contains two conserved cysteines that may form a disulphide bridge. This domain is Wnt binding in WIF, and it has been suggested that RYK may also bind to Wnt [ (PUBMED:10637605) ].
Family alignment:
There are 302 WIF domains in 302 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing WIF domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with WIF domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing WIF domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
A new secreted protein that binds to Wnt proteins and inhibits their activities.
Nature. 1999; 398: 431-6
Display abstract
The Wnt proteins constitute a large family of extracellular signalling molecules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes. Here we describe Wnt-inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and inhibits their activities. WIF-1 is present in fish, amphibia and mammals, and is expressed during Xenopus and zebrafish development in a complex pattern that includes paraxial presomitic mesoderm, notochord, branchial arches and neural crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression affects somitogenesis (the generation of trunk mesoderm segments), in agreement with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins, our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, presumably to fine-tune the spatial and temporal patterns of Wnt activity.
RYK, a receptor tyrosine kinase-related molecule with unusual kinase domain motifs.
Proc Natl Acad Sci U S A. 1992; 89: 11818-22
Display abstract
By using the polymerase chain reaction with degenerate oligonucleotides based on highly conserved motifs held in common between all members of the protein tyrosine kinase (PTK) family, a PTK-related sequence was isolated from murine peritoneal macrophage cDNA. Full-length clones have been isolated that encompass the entire coding region of the mRNA, and the predicted amino acid sequence indicates that the protein encoded has the structure of a growth factor receptor PTK (RTK). We have dubbed this molecule RYK (for related to tyrosine kinase). The RYK-encoded protein bears a transmembrane domain, with a relatively small (183 amino acid) extracellular domain, containing five potential N-linked glycosylation sites. The intracellular domain of RYK is unique among the broader family of RTKs and has several unusual sequence idiosyncrasies in some of the most highly conserved elements of the PTK domain. These sequence differences call into question the potential catalytic activity of the RYK protein.
A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans.
Nature. 1987; 326: 259-67
Display abstract
Twenty-three genes have been assigned to particular steps in a genetic pathway for the specification of the vulval cell lineages of the nematode Caenorhabditis elegans. Mutations in most of these genes cause homoeotic transformations in the fates of individual cells, suggesting that these lineages may be specified by a series of decisions that distinguish between alternative cell fates. Fifteen of the genes function in a system involved in the intracellular response to the extracellular signal that induces vulval formation.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with WIF domain which could be assigned to a KEGG orthologous group, and not all proteins containing WIF domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
