PR01843

WNT3PROTEIN

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameWNT3PROTEIN

Description
Imported from IPR009141

This entry represents the family of proto-oncogene Wnt-3 and related proteins. Wnt-3, also called proto-oncogene Int-4, functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family. The Wnt-3 gene was first identified in mouse in 1987, where it was found to be expressed during embryogenesis and in adult brain
[6]
. It is required for normal embryonic development, and especially for limb development. Wnt-3a functions in the canonical Wnt signaling pathway and plays crucial roles in both proliferation and differentiation processes in several types of stem cells
[9]
. Wnt3a stimulates the migration and invasion of trophoblasts and induce the survival, proliferation, and migration of human embryonic kidney (HEK) 293 cells. It also up-regulates genes implicated in melanocyte differentiation and increases the expression and nuclear localization of the transcriptional co-activator with PDZ-binding motif (TAZ), a transcriptional modulator involved in activating osteoblastic differentiation.

Wnt-3 structure consists of a N-terminal helical domain, a linker region and an elongated disulfide-rich C-terminal domain and very closely resembles the structure of Wnt-8
6AHY
[7]
.

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)
[1]
. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals
[5]
. 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
[2, 4]
.

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
[3]
. 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
[8]
.

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
[1]
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.

References
Imported from IPR009141

1.Mechanisms of Wnt signaling in development. Wodarz A, Nusse R. Annu. Rev. Cell Dev. Biol. 14, 59-88, (1998). View articlePMID: 9891778

2.Wnt signaling function in Alzheimer's disease. De Ferrari GV, Inestrosa NC. Brain Res. Brain Res. Rev. 33, 1-12, (2000). View articlePMID: 10967351

3.Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus. Peifer M, Polakis P. Science 287, 1606-9, (2000). View articlePMID: 10733430

4.Human dishevelled genes constitute a DHR-containing multigene family. Semenov MV, Snyder M. Genomics 42, 302-10, (1997). View articlePMID: 9192851

5.Wnt signalling shows its versatility. Bejsovec A. Curr. Biol. 9, R684-7, (1999). View articlePMID: 10508601

6.Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain. Roelink H, Wagenaar E, Lopes da Silva S, Nusse R. Proc. Natl. Acad. Sci. U.S.A. 87, 4519-23, (1990). View articlePMID: 2162045

7.Crystal structure of a mammalian Wnt-frizzled complex. Hirai H, Matoba K, Mihara E, Arimori T, Takagi J. Nat Struct Mol Biol 26, 372-379, (2019). PMID: 31036956

8.Generating a Wnt switch: it's all about the right dosage. Kestler HA, Kuhl M. J. Cell Biol. 193, 431-3, (2011). View articlePMID: 21536746

9.Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling. David MD, Canti C, Herreros J. J Neurosci Res 88, 3011-23, (2010). PMID: 20722074

Further reading

10. Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene. Roelink H, Wang J, Black DM, Solomon E, Nusse R. Genomics 17, 790-2, (1993). View articlePMID: 8244403

Supplementary References

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