2jmf

Structural highlights

Function

[SUDX_DROME] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Down-regulates Notch/N signaling pathway, probably by promoting Notch ubiquitination, endocytosis and degradation. Involved in wing growth and leg joint formation.^{[1] [2]} [NOTCH_DROME] Signaling protein, which regulates, with both positive and negative signals, the differentiation of at least central and peripheral nervous system and eye, wing disk, oogenesis, segmental appendages such as antennae and legs, and muscles, through lateral inhibition or induction. Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination. Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex. Essential for proper differentiation of ectoderm. Fringe (fng) acts in the Golgi to determine the type of O-linked fucose on the EGF modules in N, altering the ability of N to bind with Delta (Dl). O-fut1 also has a role in modulating the interaction. Rumi acts in the endoplasmic reticulum to glucosylate the EGF modules in N, this is required for correct folding and cleavage of N.^{[3] [4]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Mazaleyrat SL, Fostier M, Wilkin MB, Aslam H, Evans DA, Cornell M, Baron M. Down-regulation of Notch target gene expression by Suppressor of deltex. Dev Biol. 2003 Mar 15;255(2):363-72. PMID:12648496
2. ↑ Wilkin MB, Carbery AM, Fostier M, Aslam H, Mazaleyrat SL, Higgs J, Myat A, Evans DA, Cornell M, Baron M. Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr Biol. 2004 Dec 29;14(24):2237-44. PMID:15620650 doi:http://dx.doi.org/S0960982204008966
3. ↑ Bruckner K, Perez L, Clausen H, Cohen S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature. 2000 Jul 27;406(6794):411-5. PMID:10935637 doi:http://dx.doi.org/10.1038/35019075
4. ↑ Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell. 2008 Jan 25;132(2):247-58. doi: 10.1016/j.cell.2007.12.016. PMID:18243100 doi:http://dx.doi.org/10.1016/j.cell.2007.12.016
5. ↑ Jennings MD, Blankley RT, Baron M, Golovanov AP, Avis JM. Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex. J Biol Chem. 2007 Sep 28;282(39):29032-42. Epub 2007 Jul 26. PMID:17656366 doi:10.1074/jbc.M703453200