View source for 4ynz


==Structure of the N-terminal domain of SAD==
<StructureSection load='4ynz' size='340' side='right'caption='[[4ynz]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ynz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YNZ FirstGlance]. <br>
</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=4ynz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ynz OCA], [https://pdbe.org/4ynz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ynz RCSB], [https://www.ebi.ac.uk/pdbsum/4ynz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ynz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BRSK2_MOUSE BRSK2_MOUSE] Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-504' and 'Ser-554'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-175 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-261 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmatic reticulum (ER) stress.<ref>PMID:15705853</ref> <ref>PMID:17482548</ref> <ref>PMID:20026642</ref> <ref>PMID:22669945</ref> <ref>PMID:22798068</ref> 
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== Publication Abstract from PubMed ==
The SAD/BRSK kinases participate in various important life processes, including neural development, cell cycle and energy metabolism. Like other members of the AMPK family, SAD contains an N-terminal kinase domain followed by the characteristic UBA and KA1 domains. Here we identify a unique autoinhibitory sequence (AIS) in SAD kinases, which exerts autoregulation in cooperation with UBA. Structural studies of mouse SAD-A revealed that UBA binds to the kinase domain in a distinct mode and, more importantly, AIS nestles specifically into the KD-UBA junction. The cooperative action of AIS and UBA results in an 'alphaC-out' inactive kinase, which is conserved across species and essential for presynaptic vesicle clustering in C. elegans. In addition, the AIS, along with the KA1 domain, is indispensable for phospholipid binding. Taken together, these data suggest a model for synergistic autoinhibition and membrane activation of SAD kinases.

Structural insight into the mechanism of synergistic autoinhibition of SAD kinases.,Wu JX, Cheng YS, Wang J, Chen L, Ding M, Wu JW Nat Commun. 2015 Dec 2;6:8953. doi: 10.1038/ncomms9953. PMID:26626945<ref>PMID:26626945</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4ynz" 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: Mus musculus]]
[[Category: Chen L]]
[[Category: Wang J]]
[[Category: Wang ZX]]
[[Category: Wu JW]]
[[Category: Wu JX]]