|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2ux0' size='340' side='right'caption='[[2ux0]], [[Resolution|resolution]] 2.46Å' scene=''> | | <StructureSection load='2ux0' size='340' side='right'caption='[[2ux0]], [[Resolution|resolution]] 2.46Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ux0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UX0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UX0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ux0]] is a 6 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=2UX0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UX0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</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]] 2.46Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene></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=2ux0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ux0 OCA], [https://pdbe.org/2ux0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ux0 RCSB], [https://www.ebi.ac.uk/pdbsum/2ux0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ux0 ProSAT]</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=2ux0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ux0 OCA], [https://pdbe.org/2ux0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ux0 RCSB], [https://www.ebi.ac.uk/pdbsum/2ux0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ux0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/KCC2G_HUMAN KCC2G_HUMAN] The disease may be caused by variants affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KCC2G_HUMAN KCC2G_HUMAN] Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity).[UniProtKB:Q923T9]<ref>PMID:16690701</ref> <ref>PMID:30184290</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 34: |
Line 38: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Calcium/calmodulin-dependent protein kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bunkoczi, G]] | + | [[Category: Bunkoczi G]] |
| - | [[Category: Debreczeni, J E]] | + | [[Category: Debreczeni JE]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Edwards A]] |
| - | [[Category: Edwards, A]] | + | [[Category: Gileadi O]] |
| - | [[Category: Gileadi, O]] | + | [[Category: Knapp S]] |
| - | [[Category: Knapp, S]] | + | [[Category: Pike ACW]] |
| - | [[Category: Pike, A C.W]] | + | [[Category: Rellos P]] |
| - | [[Category: Rellos, P]] | + | [[Category: Salah E]] |
| - | [[Category: Salah, E]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Turnbull A]] |
| - | [[Category: Turnbull, A]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Von Delft F]] |
| - | [[Category: Atp-binding]] | + | |
| - | [[Category: Calmodulin]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Oligomerisation domain]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Serine- threonine kinase]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
KCC2G_HUMAN The disease may be caused by variants affecting the gene represented in this entry.
Function
KCC2G_HUMAN Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity).[UniProtKB:Q923T9][1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Long-term potentiation (LTP), a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM)-dependent kinase II (CaMKII). CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.
Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.,Rellos P, Pike AC, Niesen FH, Salah E, Lee WH, von Delft F, Knapp S PLoS Biol. 2010 Jul 27;8(7):e1000426. PMID:20668654[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rose AJ, Kiens B, Richter EA. Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise. J Physiol. 2006 Aug 1;574(Pt 3):889-903. Epub 2006 May 11. PMID:16690701 doi:http://dx.doi.org/10.1113/jphysiol.2006.111757
- ↑ Proietti Onori M, Koopal B, Everman DB, Worthington JD, Jones JR, Ploeg MA, Mientjes E, van Bon BW, Kleefstra T, Schulman H, Kushner SA, Küry S, Elgersma Y, van Woerden GM. The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function. Hum Mutat. 2018 Dec;39(12):2008-2024. PMID:30184290 doi:10.1002/humu.23647
- ↑ Rellos P, Pike AC, Niesen FH, Salah E, Lee WH, von Delft F, Knapp S. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. PLoS Biol. 2010 Jul 27;8(7):e1000426. PMID:20668654 doi:10.1371/journal.pbio.1000426
|
