4c99

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Template:STRUCTURE 4c99

Contents

Mouse ZNRF3 ectodomain in complex with mouse RSPO2 Fu1-Fu2 crystal form I

Function

[ZNRF3_MOUSE] E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.[1] [2] [RSPO2_MOUSE] Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Probably also acts as a ligand for frizzled and LRP receptors.[3]

About this Structure

4c99 is a 4 chain structure. Full crystallographic information is available from OCA.

Reference

  1. ↑ Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, Mao X, Ma Q, Zamponi R, Bouwmeester T, Finan PM, Kirschner MW, Porter JA, Serluca FC, Cong F. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012 Apr 29;485(7397):195-200. doi: 10.1038/nature11019. PMID:22575959 doi:10.1038/nature11019
  2. ↑ Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, Clevers H. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012 Aug 30;488(7413):665-9. doi: 10.1038/nature11308. PMID:22895187 doi:10.1038/nature11308
  3. ↑ Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11452-7. doi:, 10.1073/pnas.1106083108. Epub 2011 Jun 21. PMID:21693646 doi:http://dx.doi.org/10.1073/pnas.1106083108

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