|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6fd3' size='340' side='right'caption='[[6fd3]], [[Resolution|resolution]] 1.52Å' scene=''> | | <StructureSection load='6fd3' size='340' side='right'caption='[[6fd3]], [[Resolution|resolution]] 1.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6fd3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FD3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FD3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fd3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FD3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 1.52Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=T8L:'>T8L</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T8L:(2~{S},3~{R})-2-azanyl-3-[oxidanyl(sulfanyl)phosphoryl]oxy-butanoic+acid'>T8L</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAK3, OPHN3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6fd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fd3 OCA], [https://pdbe.org/6fd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fd3 RCSB], [https://www.ebi.ac.uk/pdbsum/6fd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fd3 ProSAT]</span></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=6fd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fd3 OCA], [http://pdbe.org/6fd3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fd3 RCSB], [http://www.ebi.ac.uk/pdbsum/6fd3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fd3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PAK3_HUMAN PAK3_HUMAN]] X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/PAK3_HUMAN PAK3_HUMAN] X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PAK3_HUMAN PAK3_HUMAN]] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development.<ref>PMID:21177870</ref> | + | [https://www.uniprot.org/uniprot/PAK3_HUMAN PAK3_HUMAN] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development.<ref>PMID:21177870</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 23: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | [[Category: Bountra C]] |
| - | [[Category: Bountra, C]] | + | [[Category: Edwards AM]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Elkins JM]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Sorrell FJ]] |
| - | [[Category: Elkins, J M]] | + | [[Category: Wang D]] |
| - | [[Category: Sorrell, F J]] | + | [[Category: Von Delft F]] |
| - | [[Category: Wang, D]] | + | |
| - | [[Category: Adp]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Phosphorylated]]
| + | |
| - | [[Category: Thiophosphorylation]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
PAK3_HUMAN X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.
Function
PAK3_HUMAN Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development.[1]
Publication Abstract from PubMed
The group A p21-activated kinases (PAKs) exist in an auto-inhibited form until activated by GTPase binding and auto-phosphorylation. In the auto-inhibited form, a regulatory domain binds to the kinase domain (KD) blocking the binding of substrates, and CDC42 or Rac binding to the regulatory domain relieves this auto-inhibition allowing auto-phosphorylation on the KD activation loop. We have determined the crystal structure of the PAK3 catalytic domain and by small angle X-ray scattering, the solution-phase structures of full-length inactive PAK1 and PAK3. The structures reveal a compact but elongated molecular shape that demonstrates that, together with multiple independent biophysical measurements and in contrast with previous assumptions, group A PAKs are monomeric both before and after activation, consistent with an activation mechanism of cis-auto-inhibition and initial cis-auto-phosphorylation, followed by transient dimerisation to allow trans-auto-phosphorylation for full activation, yielding a monomeric active PAK protein.
Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited in cis.,Sorrell FJ, Kilian LM, Elkins JM Biochem J. 2019 Apr 4;476(7):1037-1051. doi: 10.1042/BCJ20180867. PMID:30858169[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Deleris P, Trost M, Topisirovic I, Tanguay PL, Borden KL, Thibault P, Meloche S. Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway. J Biol Chem. 2011 Feb 25;286(8):6470-8. doi: 10.1074/jbc.M110.181529. Epub 2010, Dec 22. PMID:21177870 doi:http://dx.doi.org/10.1074/jbc.M110.181529
- ↑ Sorrell FJ, Kilian LM, Elkins JM. Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited in cis. Biochem J. 2019 Apr 4;476(7):1037-1051. doi: 10.1042/BCJ20180867. PMID:30858169 doi:http://dx.doi.org/10.1042/BCJ20180867
|
