Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (PubMed:25731175). Also acts as a regulator of long-range activity of Hedgehog (hh), possibly by regulating the switch between low and high level hh pathway signaling (PubMed:20412775, PubMed:22872085). [Wnt protein]-O-(9Z)-hexadecenoyl-L-serine + H2O = (9Z)-hexadecenoate + [Wnt protein]-L-serine + H(+) Associates with the cell surface via interaction with sulfated CAG chains on glypicans. Expression is induced by Wnt. Belongs to the pectinacetylesterase family. Notum subfamily. The molecular function of NOTUM has remained unclear for many years. It was initially thought to hydrolyze glycosaminoglycan (GAG) chains of glypicans, thereby affecting glypicans ability to interact with Wnt ligands (PubMed:12015973, PubMed:12000788). It was later reported to trigger glypican shedding, by mediating cleavage of their GPI-anchor (PubMed:15469839). However, while NOTUM specifically inhibit the Wnt signaling pathway, more pleiotropic effects would be expected from an enzyme affecting glypicans. It was finally shown that it requires glypicans to suppress Wnt signaling, but does not cleave their GPI-anchor (PubMed:25731175). It acts by mediating depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled receptors (PubMed:25731175). The art of biocuration - Issue 177 of March 2016