Short name: Wnt
- Wnt (IPR005817)
- Wnt inhibitor of Dorsal protein (IPR026540)
- Wnt-1 protein (IPR009139)
- Wnt-10 protein (IPR013302)
- Wnt-11 protein (IPR026536)
- Wnt-16 protein (IPR013304)
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) [PMID: 9891778]. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals [PMID: 10508601]. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [PMID: 10967351, PMID: 9192851].
Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development [PMID: 10733430]. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [PMID: 21536746].
Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [PMID: 9891778] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.
In humans, 19 Wnt proteins have been identified that share 27% to 83% amino-acid sequence identity and a conserved pattern of 23 or 24 cysteine residues [PMID: 11806834]. Wnt genes are highly conserved between vertebrate species sharing overall sequence identity and gene structure, and are slightly less conserved between vertebrates and invertebrates.