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| - | [[Image:1a06.jpg|left|200px]]<br /><applet load="1a06" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1a06, resolution 2.5Å" /> | |
| - | '''CALMODULIN-DEPENDENT PROTEIN KINASE FROM RAT'''<br /> | |
| | | | |
| - | ==Overview== | + | ==CALMODULIN-DEPENDENT PROTEIN KINASE FROM RAT== |
| - | The crystal structure of calcium/calmodulin-dependent protein kinase I has, been determined in the autoinhibited form. The C-terminal regulatory, region of the enzyme forms a helix-loop-helix segment that extends across, the two domains of the catalytic core, making multiple inhibitory, interactions. Elements of the first regulatory alpha helix and the loop, interfere with the binding site for peptide substrates, while the loop and, the second helix interact with the ATP-binding domain to induce, conformational changes that obstruct the nucleotide binding pocket. One, part of the calmodulin recognition element protrudes away from the, catalytic domain and is potentially available for an initial interaction, with calmodulin. The structure provides a view of an intact calmodulin, target and suggests that substantial structural changes will accompany, kinase activation by calmodulin binding to the regulatory region.
| + | <StructureSection load='1a06' size='340' side='right'caption='[[1a06]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1a06]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A06 FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=1a06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a06 OCA], [https://pdbe.org/1a06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a06 RCSB], [https://www.ebi.ac.uk/pdbsum/1a06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a06 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KCC1A_RAT KCC1A_RAT] Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-516', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation (By similarity). Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-275' and 'Ser-294'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.<ref>PMID:1646483</ref> <ref>PMID:8621702</ref> <ref>PMID:12081505</ref> <ref>PMID:15084659</ref> <ref>PMID:15689566</ref> <ref>PMID:17022975</ref> <ref>PMID:16772171</ref> <ref>PMID:21107644</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a0/1a06_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1a06 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | 1A06 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A06 OCA].
| + | *[[Calcium/calmodulin dependent protein kinase 3D structures|Calcium/calmodulin dependent protein kinase 3D structures]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I., Goldberg J, Nairn AC, Kuriyan J, Cell. 1996 Mar 22;84(6):875-87. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8601311 8601311]
| + | __TOC__ |
| - | [[Category: Calcium/calmodulin-dependent protein kinase]] | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
| - | [[Category: Single protein]]
| + | [[Category: Goldberg J]] |
| - | [[Category: Goldberg, J.]] | + | [[Category: Kuriyan J]] |
| - | [[Category: Kuriyan, J.]] | + | |
| - | [[Category: calcium/calmodulin]]
| + | |
| - | [[Category: kinase]]
| + | |
| - | [[Category: signal transduction]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:31:42 2007''
| + | |
| Structural highlights
Function
KCC1A_RAT Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-516', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation (By similarity). Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-275' and 'Ser-294'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.[1] [2] [3] [4] [5] [6] [7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Sheng M, Thompson MA, Greenberg ME. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991 Jun 7;252(5011):1427-30. PMID:1646483
- ↑ Sun P, Lou L, Maurer RA. Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV. J Biol Chem. 1996 Feb 9;271(6):3066-73. PMID:8621702
- ↑ Suizu F, Fukuta Y, Ueda K, Iwasaki T, Tokumitsu H, Hosoya H. Characterization of Ca2+/calmodulin-dependent protein kinase I as a myosin II regulatory light chain kinase in vitro and in vivo. Biochem J. 2002 Oct 15;367(Pt 2):335-45. PMID:12081505 doi:10.1042/BJ20020536
- ↑ Wayman GA, Kaech S, Grant WF, Davare M, Impey S, Tokumitsu H, Nozaki N, Banker G, Soderling TR. Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I. J Neurosci. 2004 Apr 14;24(15):3786-94. PMID:15084659 doi:10.1523/JNEUROSCI.3294-03.2004
- ↑ Schmitt JM, Guire ES, Saneyoshi T, Soderling TR. Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase-dependent long-term potentiation. J Neurosci. 2005 Feb 2;25(5):1281-90. PMID:15689566 doi:10.1523/JNEUROSCI.4086-04.2005
- ↑ Tokumitsu H, Hatano N, Yokokura S, Sueyoshi Y, Nozaki N, Kobayashi R. Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2. FEBS Lett. 2006 Oct 16;580(24):5797-801. Epub 2006 Sep 27. PMID:17022975 doi:10.1016/j.febslet.2006.09.043
- ↑ Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, Soderling TR. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006 Jun 15;50(6):897-909. PMID:16772171 doi:10.1016/j.neuron.2006.05.008
- ↑ Davare MA, Saneyoshi T, Soderling TR. Calmodulin-kinases regulate basal and estrogen stimulated medulloblastoma migration via Rac1. J Neurooncol. 2011 Aug;104(1):65-82. doi: 10.1007/s11060-010-0472-6. Epub 2010, Nov 24. PMID:21107644 doi:10.1007/s11060-010-0472-6
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