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| | ==Calmodulin wraps around its binding domain in the plasma membrane CA2+ pump anchored by a novel 18-1 motif== | | ==Calmodulin wraps around its binding domain in the plasma membrane CA2+ pump anchored by a novel 18-1 motif== |
| - | <StructureSection load='2kne' size='340' side='right'caption='[[2kne]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kne' size='340' side='right'caption='[[2kne]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KNE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KNE FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALM, CALM1, CALM2, CALM3, CALML2, CAM, CAM1, CAM2, CAM3, CAMB, CAMC, CAMIII ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ATP2B4, hCG_18445, RP11-397P13.1-001 ([https://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=2kne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kne OCA], [https://pdbe.org/2kne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kne RCSB], [https://www.ebi.ac.uk/pdbsum/2kne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kne 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=2kne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kne OCA], [https://pdbe.org/2kne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kne RCSB], [https://www.ebi.ac.uk/pdbsum/2kne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kne ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/AT2B4_HUMAN AT2B4_HUMAN]] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
| + | [https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Atanasova, E]] | + | [[Category: Atanasova E]] |
| - | [[Category: Filoteo, A G]] | + | [[Category: Filoteo AG]] |
| - | [[Category: Juranic, N]] | + | [[Category: Juranic N]] |
| - | [[Category: Macura, S]] | + | [[Category: Macura S]] |
| - | [[Category: Penniston, J T]] | + | [[Category: Penniston JT]] |
| - | [[Category: Prendergast, F G]] | + | [[Category: Prendergast FG]] |
| - | [[Category: Strehler, E E]] | + | [[Category: Strehler EE]] |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Calcium]]
| + | |
| - | [[Category: Calcium pump]]
| + | |
| - | [[Category: Calmodulin]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Isopeptide bond]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal transport]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protein/peptide]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Ubl conjugation]]
| + | |
| Structural highlights
Disease
CALM1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.
Function
CALM1_HUMAN Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4]
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
Using solution NMR spectroscopy, we obtained the structure of Ca(2+)-calmodulin (holoCaM) in complex with peptide C28 from the binding domain of the plasma membrane Ca(2+)-ATPase (PMCA) pump isoform 4b. This provides the first atomic resolution insight into the binding mode of holoCaM to the full-length binding domain of PMCA. Structural comparison of the previously determined holoCaM.C20 complex with this holoCaM.C28 complex supports the idea that the initial binding step is represented by (holoCaM.C20) and the final bound complex by (holoCaM.C28). This affirms the existing multi-step kinetic model of PMCA4b activation by CaM. The complex exhibits a new binding motif in which holoCaM is wrapped around helical C28 peptide using two anchoring residues from the peptide at relative positions 18 and 1. The anchors correspond to Phe-1110 and Trp-1093, respectively, in full-length PMCA4b, and the peptide and CaM are oriented in an anti-parallel manner. This is a greater sequence distance between anchors than in any of the known holoCaM complexes with a helical peptide. Analysis of the geometry of holoCaM-peptide binding for the cases where the target peptide adopts an alpha(D)-helix with its anchors buried in the main hydrophobic pockets of the two CaM lobes establishes that only relative sequential positions of 10, 14, 17, and 18 are allowed for the second anchor.
Calmodulin wraps around its binding domain in the plasma membrane Ca2+ pump anchored by a novel 18-1 motif.,Juranic N, Atanasova E, Filoteo AG, Macura S, Prendergast FG, Penniston JT, Strehler EE J Biol Chem. 2010 Feb 5;285(6):4015-24. Epub 2009 Dec 7. PMID:19996092[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
- ↑ Reichow SL, Clemens DM, Freites JA, Nemeth-Cahalan KL, Heyden M, Tobias DJ, Hall JE, Gonen T. Allosteric mechanism of water-channel gating by Ca-calmodulin. Nat Struct Mol Biol. 2013 Jul 28. doi: 10.1038/nsmb.2630. PMID:23893133 doi:10.1038/nsmb.2630
- ↑ Boczek NJ, Gomez-Hurtado N, Ye D, Calvert ML, Tester DJ, Kryshtal D, Hwang HS, Johnson CN, Chazin WJ, Loporcaro CG, Shah M, Papez AL, Lau YR, Kanter R, Knollmann BC, Ackerman MJ. Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G. Circ Cardiovasc Genet. 2016 Apr;9(2):136-146. doi:, 10.1161/CIRCGENETICS.115.001323. Epub 2016 Mar 11. PMID:26969752 doi:http://dx.doi.org/10.1161/CIRCGENETICS.115.001323
- ↑ Yu CC, Ko JS, Ai T, Tsai WC, Chen Z, Rubart M, Vatta M, Everett TH 4th, George AL Jr, Chen PS. Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current. Heart Rhythm. 2016 Aug;13(8):1716-23. doi: 10.1016/j.hrthm.2016.05.009. Epub 2016, May 7. PMID:27165696 doi:http://dx.doi.org/10.1016/j.hrthm.2016.05.009
- ↑ Juranic N, Atanasova E, Filoteo AG, Macura S, Prendergast FG, Penniston JT, Strehler EE. Calmodulin wraps around its binding domain in the plasma membrane Ca2+ pump anchored by a novel 18-1 motif. J Biol Chem. 2010 Feb 5;285(6):4015-24. Epub 2009 Dec 7. PMID:19996092 doi:10.1074/jbc.M109.060491
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