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5yh3

From Proteopedia

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Current revision

The structure of hFam20C and hFam20A complex

Structural highlights

5yh3 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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. [FA20C_HUMAN] Lethal osteosclerotic bone dysplasia. 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] [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).^[2] ^[3] ^[4] ^[5]

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^[6]

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
↑ Tagliabracci VS, Engel JL, Wen J, Wiley SE, Worby CA, Kinch LN, Xiao J, Grishin NV, Dixon JE. Secreted kinase phosphorylates extracellular proteins that regulate biomineralization. Science. 2012 Jun 1;336(6085):1150-3. doi: 10.1126/science.1217817. Epub 2012 May, 10. PMID:22582013 doi:http://dx.doi.org/10.1126/science.1217817
↑ Xiao J, Tagliabracci VS, Wen J, Kim SA, Dixon JE. Crystal structure of the Golgi casein kinase. Proc Natl Acad Sci U S A. 2013 Jun 10. PMID:23754375 doi:10.1073/pnas.1309211110
↑ 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
↑ Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE. A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. PMID:26091039 doi:http://dx.doi.org/10.1016/j.cell.2015.05.028
↑ Zhang H, Zhu Q, Cui J, Wang Y, Chen MJ, Guo X, Tagliabracci VS, Dixon JE, Xiao J. Structure and evolution of the Fam20 kinases. Nat Commun. 2018 Mar 23;9(1):1218. doi: 10.1038/s41467-018-03615-z. PMID:29572475 doi:http://dx.doi.org/10.1038/s41467-018-03615-z

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5yh3"

@@ Line 1: / Line 1: @@
 ==The structure of hFam20C and hFam20A complex==
-<StructureSection load='5yh3' size='340' side='right' caption='[[5yh3]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+<StructureSection load='5yh3' size='340' side='right'caption='[[5yh3]], [[Resolution|resolution]] 3.30&Aring;' 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>
+<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://proteopedia.org/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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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 ==
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 5yh3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Xiao, J]]

5yh3

From Proteopedia

Current revision

The structure of hFam20C and hFam20A complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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