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| | <StructureSection load='5wrr' size='340' side='right'caption='[[5wrr]], [[Resolution|resolution]] 2.51Å' scene=''> | | <StructureSection load='5wrr' size='340' side='right'caption='[[5wrr]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wrr]] 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=5WRR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WRR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wrr]] 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=5WRR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WRR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.506Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wrs|5wrs]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAM20A, UNQ9388/PRO34279 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5wrr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wrr OCA], [https://pdbe.org/5wrr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wrr RCSB], [https://www.ebi.ac.uk/pdbsum/5wrr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wrr ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5wrr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wrr OCA], [http://pdbe.org/5wrr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wrr RCSB], [http://www.ebi.ac.uk/pdbsum/5wrr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wrr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/FA20A_HUMAN FA20A_HUMAN]] Amelogenesis imperfecta - nephrocalcinosis;Amelogenesis imperfecta and gingival hyperplasia syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/FA20A_HUMAN FA20A_HUMAN] Amelogenesis imperfecta - nephrocalcinosis;Amelogenesis imperfecta and gingival hyperplasia syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FA20A_HUMAN FA20A_HUMAN]] Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth. Forms a complex with FAM20C and increases the ability of FAM20C to phosphorylate the proteins that form the 'matrix' that guides the deposition of the enamel minerals.<ref>PMID:25789606</ref> | + | [https://www.uniprot.org/uniprot/FA20A_HUMAN FA20A_HUMAN] Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth. Forms a complex with FAM20C and increases the ability of FAM20C to phosphorylate the proteins that form the 'matrix' that guides the deposition of the enamel minerals.<ref>PMID:25789606</ref> |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Zhu, Q]] | + | [[Category: Zhu Q]] |
| - | [[Category: Secretory pathway pseudokinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
FA20A_HUMAN Amelogenesis imperfecta - nephrocalcinosis;Amelogenesis imperfecta and gingival hyperplasia syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
FA20A_HUMAN Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth. Forms a complex with FAM20C and increases the ability of FAM20C to phosphorylate the proteins that form the 'matrix' that guides the deposition of the enamel minerals.[1]
Publication Abstract from PubMed
Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique insertion region. Loss of this insertion due to abnormal mRNA splicing interferes with the structure and function of Fam20A, resulting in AI. Fam20A binds ATP in the absence of divalent cations, and strikingly, ATP is bound in an inverted orientation compared to other kinases. Fam20A forms a dimer in the crystal, and residues in the dimer interface are critical for Fam20C activation. Together, these results provide structural insights into the function of Fam20A and shed light on the mechanism by which Fam20A mutations cause disease.
Structure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern and inverted ATP-binding.,Cui J, Zhu Q, Zhang H, Cianfrocco MA, Leschziner AE, Dixon JE, Xiao J Elife. 2017 Apr 22;6. pii: e23990. doi: 10.7554/eLife.23990. PMID:28432788[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cui J, Xiao J, Tagliabracci VS, Wen J, Rahdar M, Dixon JE. A secretory kinase complex regulates extracellular protein phosphorylation. Elife. 2015 Mar 19;4:e06120. doi: 10.7554/eLife.06120. PMID:25789606 doi:http://dx.doi.org/10.7554/eLife.06120
- ↑ Cui J, Zhu Q, Zhang H, Cianfrocco MA, Leschziner AE, Dixon JE, Xiao J. Structure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern and inverted ATP-binding. Elife. 2017 Apr 22;6. pii: e23990. doi: 10.7554/eLife.23990. PMID:28432788 doi:http://dx.doi.org/10.7554/eLife.23990
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