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5iri

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Revision as of 07:28, 3 June 2020

Structure of the mouse SAD-B AIS-KA1 fragment

Structural highlights

5iri is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Brsk1, Gm1100, Sadb (LK3 transgenic mice)
Activity:	[Tau_protein_kinase [Tau protein] kinase], with EC number 2.7.11.26
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Structure of the mouse SAD-B AIS-KA1 fragment==
-<StructureSection load='5iri' size='340' side='right' caption='[[5iri]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='5iri' size='340' side='right'caption='[[5iri]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5iri]] is a 2 chain structure. 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IRI FirstGlance]. <br>
+<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>
-</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>
+</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>
-<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=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]</span></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'>[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>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5iri" 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: Lk3 transgenic mice]]
 [[Category: Ma, H]]
 [[Category: Wang, J]]

5iri

From Proteopedia

Revision as of 07:28, 3 June 2020

Structure of the mouse SAD-B AIS-KA1 fragment

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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