Porcupine
The Porcupine (Porc) protein may be involved in secretion or ER transport, as Wingless is retained in the ER in porcupine mutant Drosophila embryos (Kadowaki 1996, van den Heuvel 1993). In C. elegans, the porcupine homolog mom-1 has a similar function in promoting secretion of the Wnt protein Mom-2 (Rocheleau 1997). Porcupine has some homology to a family of o-acyl transferases and may be involved in lipid modification of Wnt proteins (Hofmann, 2000, Willert 2003, Zhai, 2004). A special form of monounsaturated palmitoylation has been detected on a serine residue in the Wnt protein (Takada 2006) and could be mediated by porc as well.
Several small molecules, including IWP, have been shown to be effective in blocking Wnt secretion through directly targeting Porcupine. These molecules are used widely in experimental settings and are being tested in clinical trials as well.
There appears to be a single Porcupine gene in the mouse, human and Drosophila genomes,although the family of general acyl-transferases is large. The Drosophila ski/sit/rasp gene which operates in Hedgehog signaling, is also a member of this family.
The human Porcupine gene is implicated in a genetic disease, Focal dermal hypoplasia (Grzeschik 2007 , Wang 2007)
Human |
Drosophila |
Mouse |
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PORCN | por | Mutants described by Barrott, 2011 and Biechele, 2011, Gastrulation phenotype (Biechele 2013) |