Wnt inhibitory factor (WIF)-1 (IPR013309)

Short name: Wnt-inh

Overlapping homologous superfamilies

Family relationships



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.

Wnt inhibitory factor-1 (WIF-1) is a secreted protein that binds to Wnt proteins and inhibits their activities. It was first identified as an EST from human retina; ortholgues have since been identified in mouse, rat, Xenopus and zebrafish. WIF-1 proteins comprise an N-terminal signal sequence, a family-specific WIF domain, five epidermal growth factor (EGF) repeats and a hydrophilic C terminus. The interaction of Wnt proteins with WIF-1 and other inhibitors, such as frizzled-related protein, is thought to fine tune their activity [PMID: 10201374].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.