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| | <StructureSection load='5iri' size='340' side='right'caption='[[5iri]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='5iri' size='340' side='right'caption='[[5iri]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5iri]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IRI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IRI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5iri]] 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=5IRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IRI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Brsk1, Gm1100, Sadb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 2.8Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </span></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=5iri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iri OCA], [https://pdbe.org/5iri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iri RCSB], [https://www.ebi.ac.uk/pdbsum/5iri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iri 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=5iri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iri OCA], [http://pdbe.org/5iri PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iri RCSB], [http://www.ebi.ac.uk/pdbsum/5iri PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iri ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRSK1_MOUSE BRSK1_MOUSE]] Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 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. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C.<ref>PMID:15705853</ref> <ref>PMID:17482548</ref> <ref>PMID:19648910</ref> <ref>PMID:20026642</ref> | + | [https://www.uniprot.org/uniprot/BRSK1_MOUSE BRSK1_MOUSE] Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 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. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C.<ref>PMID:15705853</ref> <ref>PMID:17482548</ref> <ref>PMID:19648910</ref> <ref>PMID:20026642</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ma, H]] | + | [[Category: Ma H]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Wu, J W]] | + | [[Category: Wu JW]] |
| - | [[Category: Wu, J X]] | + | [[Category: Wu JX]] |
| - | [[Category: Auto-inhibition]]
| + | |
| - | [[Category: Kinase associate-1 domain]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
BRSK1_MOUSE Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 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. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C.[1] [2] [3] [4]
Publication Abstract from PubMed
The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 A resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity.
Structure and inhibition analysis of the mouse SAD-B C-terminal fragment.,Ma H, Wu JX, Wang J, Wang ZX, Wu JW Biosci Biotechnol Biochem. 2016 Jun 2:1-8. PMID:27251228[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kishi M, Pan YA, Crump JG, Sanes JR. Mammalian SAD kinases are required for neuronal polarization. Science. 2005 Feb 11;307(5711):929-32. PMID:15705853 doi:http://dx.doi.org/307/5711/929
- ↑ Barnes AP, Lilley BN, Pan YA, Plummer LJ, Powell AW, Raines AN, Sanes JR, Polleux F. LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell. 2007 May 4;129(3):549-63. PMID:17482548 doi:http://dx.doi.org/10.1016/j.cell.2007.03.025
- ↑ Alvarado-Kristensson M, Rodriguez MJ, Silio V, Valpuesta JM, Carrera AC. SADB phosphorylation of gamma-tubulin regulates centrosome duplication. Nat Cell Biol. 2009 Sep;11(9):1081-92. Epub 2009 Aug 2. PMID:19648910 doi:http://dx.doi.org/ncb1921
- ↑ Muller M, Lutter D, Puschel AW. Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity. J Cell Sci. 2010 Jan 15;123(Pt 2):286-94. doi: 10.1242/jcs.058230. Epub 2009 Dec , 21. PMID:20026642 doi:http://dx.doi.org/10.1242/jcs.058230
- ↑ Ma H, Wu JX, Wang J, Wang ZX, Wu JW. Structure and inhibition analysis of the mouse SAD-B C-terminal fragment. Biosci Biotechnol Biochem. 2016 Jun 2:1-8. PMID:27251228 doi:http://dx.doi.org/10.1080/09168451.2016.1191331
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