5yh3
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The structure of hFam20C and hFam20A complex== |
| + | <StructureSection load='5yh3' size='340' side='right' caption='[[5yh3]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5yh3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YH3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YH3 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5yh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yh3 OCA], [http://pdbe.org/5yh3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yh3 RCSB], [http://www.ebi.ac.uk/pdbsum/5yh3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yh3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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. [[http://www.uniprot.org/uniprot/FA20C_HUMAN FA20C_HUMAN]] Lethal osteosclerotic bone dysplasia. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == 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> [[http://www.uniprot.org/uniprot/FA20C_HUMAN FA20C_HUMAN]] Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth (PubMed:22582013, PubMed:23754375, PubMed:25789606). Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (PubMed:26091039). Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity (PubMed:26091039). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1 (PubMed:22582013, PubMed:25789606). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (PubMed:26091039).<ref>PMID:22582013</ref> <ref>PMID:23754375</ref> <ref>PMID:25789606</ref> <ref>PMID:26091039</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Fam20 proteins are novel kinases that phosphorylate secreted proteins and proteoglycans. Fam20C phosphorylates hundreds of secreted proteins and is activated by the pseudokinase Fam20A. Fam20B phosphorylates a xylose residue to regulate proteoglycan synthesis. Despite these wide-ranging and important functions, the molecular and structural basis for the regulation and substrate specificity of these kinases are unknown. Here we report molecular characterizations of all three Fam20 kinases, and show that Fam20C is activated by the formation of an evolutionarily conserved homodimer or heterodimer with Fam20A. Fam20B has a unique active site for recognizing Galbeta1-4Xylbeta1, the initiator disaccharide within the tetrasaccharide linker region of proteoglycans. We further show that in animals the monomeric Fam20B preceded the appearance of the dimeric Fam20C, and the dimerization trait of Fam20C emerged concomitantly with a change in substrate specificity. Our results provide comprehensive structural, biochemical, and evolutionary insights into the function of the Fam20 kinases. | ||
| - | + | Structure and evolution of the Fam20 kinases.,Zhang H, Zhu Q, Cui J, Wang Y, Chen MJ, Guo X, Tagliabracci VS, Dixon JE, Xiao J Nat Commun. 2018 Mar 23;9(1):1218. doi: 10.1038/s41467-018-03615-z. PMID:29572475<ref>PMID:29572475</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5yh3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Xiao, J]] | [[Category: Xiao, J]] | ||
[[Category: Zhu, Q]] | [[Category: Zhu, Q]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 05:29, 25 April 2018
The structure of hFam20C and hFam20A complex
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