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| | <StructureSection load='4uzq' size='340' side='right'caption='[[4uzq]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='4uzq' size='340' side='right'caption='[[4uzq]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uzq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UZQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UZQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uzq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UZQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uyu|4uyu]], [[4uyw|4uyw]], [[4uyz|4uyz]], [[4uz1|4uz1]], [[4uz5|4uz5]], [[4uz6|4uz6]], [[4uz7|4uz7]], [[4uz9|4uz9]], [[4uza|4uza]], [[4uzj|4uzj]], [[4uzk|4uzk]], [[4uzl|4uzl]], [[4wbh|4wbh]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4uzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uzq OCA], [https://pdbe.org/4uzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uzq RCSB], [https://www.ebi.ac.uk/pdbsum/4uzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uzq ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uzq OCA], [http://pdbe.org/4uzq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uzq RCSB], [http://www.ebi.ac.uk/pdbsum/4uzq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uzq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN]] Phocomelia, Schinzel type;Fuhrmann syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN]] May deacetylate GlcNAc residues on cell surface glycans. [[http://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN]] Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. Signaling by Wnt-7a allows sexually dimorphic development of the mullerian ducts (By similarity). | + | [https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carboxylesterase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Jones EY]] |
| - | [[Category: Zebisch, M]] | + | [[Category: Zebisch M]] |
| - | [[Category: Alpha/beta hydrolase]]
| + | |
| - | [[Category: Esterase]]
| + | |
| - | [[Category: Extracellular]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
NOTUM_HUMAN May deacetylate GlcNAc residues on cell surface glycans.
Publication Abstract from PubMed
Signalling by Wnt proteins is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnt proteins from the cell surface. However, this view fails to explain specificity, as glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which probably help Notum to co-localize with Wnt proteins. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.
Notum deacylates Wnt proteins to suppress signalling activity.,Kakugawa S, Langton PF, Zebisch M, Howell SA, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP Nature. 2015 Mar 12;519(7542):187-92. doi: 10.1038/nature14259. Epub 2015 Feb 25. PMID:25731175[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kakugawa S, Langton PF, Zebisch M, Howell SA, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP. Notum deacylates Wnt proteins to suppress signalling activity. Nature. 2015 Mar 12;519(7542):187-92. doi: 10.1038/nature14259. Epub 2015 Feb 25. PMID:25731175 doi:http://dx.doi.org/10.1038/nature14259
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