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| | ==Crystal structure of human calcium/calmodulin-dependent protein kinase I apo form== | | ==Crystal structure of human calcium/calmodulin-dependent protein kinase I apo form== |
| - | <StructureSection load='4fgb' size='340' side='right' caption='[[4fgb]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4fgb' size='340' side='right'caption='[[4fgb]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fgb]] 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=4FGB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FGB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fgb]] 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=4FGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FGB FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fg7|4fg7]], [[4fg8|4fg8]], [[4fg9|4fg9]]</td></tr> | + | </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=4fgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fgb OCA], [https://pdbe.org/4fgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fgb RCSB], [https://www.ebi.ac.uk/pdbsum/4fgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fgb ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAMK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=4fgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fgb OCA], [http://pdbe.org/4fgb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fgb RCSB], [http://www.ebi.ac.uk/pdbsum/4fgb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fgb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KCC1A_HUMAN KCC1A_HUMAN]] 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-694', 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. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. 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:11114197</ref> <ref>PMID:12193581</ref> <ref>PMID:14507913</ref> <ref>PMID:14754892</ref> <ref>PMID:17056143</ref> <ref>PMID:17442826</ref> <ref>PMID:18184567</ref> <ref>PMID:20181577</ref> | + | [https://www.uniprot.org/uniprot/KCC1A_HUMAN KCC1A_HUMAN] 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-694', 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. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. 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:11114197</ref> <ref>PMID:12193581</ref> <ref>PMID:14507913</ref> <ref>PMID:14754892</ref> <ref>PMID:17056143</ref> <ref>PMID:17442826</ref> <ref>PMID:18184567</ref> <ref>PMID:20181577</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4fgb" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4fgb" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Calcium/calmodulin dependent protein kinase 3D structures|Calcium/calmodulin dependent protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Calcium/calmodulin-dependent protein kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Ding, J]] | + | [[Category: Ding J]] |
| - | [[Category: Han, L]] | + | [[Category: Han L]] |
| - | [[Category: Ou, Y]] | + | [[Category: Ou Y]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Zha, M]] | + | [[Category: Zha M]] |
| - | [[Category: Zhong, C]] | + | [[Category: Zhong C]] |
| - | [[Category: Autoinhibition]]
| + | |
| - | [[Category: Calmodulin]]
| + | |
| - | [[Category: Camk]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Regulation mechanism]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KCC1A_HUMAN 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-694', 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. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. 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]
Publication Abstract from PubMed
Human calcium/calmodulin-dependent protein kinase I (CaMKI) plays pivotal roles in the nervous system. The activity of human CaMKI is regulated by a regulatory region including an autoinhibitory segment and a CaM-binding segment. We report here four structures of three CaMKIalpha truncates in apo form and in complexes with ATP. In an apo, autoinhibited structure, the activation segment adopts a unique helical conformation which together with the autoinhibitory segment constrains helices alphaC and alphaD in inactive conformations, sequesters Thr177 from being phosphorylated, and occludes the substrate-binding site. In an ATP-bound, inactive structure, the activation segment is largely disordered and the CaM-binding segment protrudes out ready for CaM binding. In an ATP-bound, active structure, the regulatory region is dissociated from the catalytic core and the catalytic site assumes an active conformation. Detailed structural analyses reveal the interplay of the regulatory region, the activation segment, and the nucleotide-binding site in the regulation of CaMKI.
Crystal structures of human CaMKIalpha reveal insights into the regulation mechanism of CaMKI.,Zha M, Zhong C, Ou Y, Han L, Wang J, Ding J PLoS One. 2012;7(9):e44828. doi: 10.1371/journal.pone.0044828. Epub 2012 Sep 20. PMID:23028635[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McKinsey TA, Zhang CL, Olson EN. Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14400-5. PMID:11114197 doi:http://dx.doi.org/10.1073/pnas.260501497
- ↑ Condon JC, Pezzi V, Drummond BM, Yin S, Rainey WE. Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Endocrinology. 2002 Sep;143(9):3651-7. PMID:12193581 doi:http://dx.doi.org/10.1210/en.2001-211359
- ↑ Qin H, Raught B, Sonenberg N, Goldstein EG, Edelman AM. Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I. J Biol Chem. 2003 Dec 5;278(49):48570-9. Epub 2003 Sep 24. PMID:14507913 doi:http://dx.doi.org/10.1074/jbc.M308781200
- ↑ Kahl CR, Means AR. Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I. J Biol Chem. 2004 Apr 9;279(15):15411-9. Epub 2004 Jan 30. PMID:14754892 doi:http://dx.doi.org/10.1074/jbc.M312543200
- ↑ Kamata A, Sakagami H, Tokumitsu H, Owada Y, Fukunaga K, Kondo H. Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth. Neurosci Res. 2007 Jan;57(1):86-97. Epub 2006 Oct 23. PMID:17056143 doi:http://dx.doi.org/10.1016/j.neures.2006.09.013
- ↑ Uboha NV, Flajolet M, Nairn AC, Picciotto MR. A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity regulating kinase 2 signaling cascade mediates calcium-dependent neurite outgrowth. J Neurosci. 2007 Apr 18;27(16):4413-23. PMID:17442826 doi:http://dx.doi.org/10.1523/JNEUROSCI.0725-07.2007
- ↑ Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR. Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron. 2008 Jan 10;57(1):94-107. doi: 10.1016/j.neuron.2007.11.016. PMID:18184567 doi:http://dx.doi.org/10.1016/j.neuron.2007.11.016
- ↑ Neal AP, Molina-Campos E, Marrero-Rosado B, Bradford AB, Fox SM, Kovalova N, Hannon HE. CaMKK-CaMKI signaling pathways differentially control axon and dendrite elongation in cortical neurons. J Neurosci. 2010 Feb 24;30(8):2807-9. doi: 10.1523/JNEUROSCI.5984-09.2010. PMID:20181577 doi:http://dx.doi.org/10.1523/JNEUROSCI.5984-09.2010
- ↑ Zha M, Zhong C, Ou Y, Han L, Wang J, Ding J. Crystal structures of human CaMKIalpha reveal insights into the regulation mechanism of CaMKI. PLoS One. 2012;7(9):e44828. doi: 10.1371/journal.pone.0044828. Epub 2012 Sep 20. PMID:23028635 doi:http://dx.doi.org/10.1371/journal.pone.0044828
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