NOTUM releases Hh-Np:GPC5 from the plasma membrane

Stable Identifier
Reaction [transition]
Homo sapiens
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Notum is a secreted protein with phospholipase C activity that has been implicated in promoting long range Hh signaling in Drosophila (Ayers et al, 2010; Eugster et al, 2007; Takeo et al, 2005; Han et al, 2005; Giraldez et al, 2002). Notum is thought to cleave the GPI-anchor from Dally, a Drosophila glypican, to release Hh-Dally complexes from the plasma membrane of the Hh-secreting cell (Ayers et al, 2010; Han et al, 2005), although this cleavage has not been directly demonstrated. In cultured mammalian cells, NOTUM has been shown to cleave the GPI anchor of a number of glypicans to promote their release from the plasma membrane (Traister et al, 2008).

Literature References
PubMed ID Title Journal Year
12015973 HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient

Copley, RR, Cohen, SM, Giráldez, AJ

Dev. Cell 2002
15963974 Expression of a secreted form of Dally, a Drosophila glypican, induces overgrowth phenotype by affecting action range of Hedgehog

Akiyama, T, Firkus, C, Nakato, H, Aigaki, T, Takeo, S

Dev. Biol. 2005
17967162 Mammalian Notum induces the release of glypicans and other GPI-anchored proteins from the cell surface

Filmus, J, Traister, A, Shi, W

Biochem. J. 2008
15647319 Drosophila glypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc

Lin, X, Yan, D, Han, C, Belenkaya, TY

Development 2005
17609110 Lipoprotein-heparan sulfate interactions in the Hh pathway

Eugster, C, Mahmoud, A, Eaton, S, Panáková, D

Dev. Cell 2007
20412775 The long-range activity of Hedgehog is regulated in the apical extracellular space by the glypican Dally and the hydrolase Notum

Gallet, A, Ayers, KL, Thérond, PP, Staccini-Lavenant, L

Dev. Cell 2010
Catalyst Activity

phospholipase C activity of NOTUM [extracellular region]

Orthologous Events
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