| 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]
Publication Abstract from PubMed
Inositol 1,4,5-triphoshate 3-kinase (IP3 3-K) is a key enzyme that catalyses the synthesis of inositol 1,3,4,5-tetrakisphosphate (IP4), using IP3 and ATP as substrates. Both inositides, substrate and product, present crucial roles in the cell. IP3 is a key point in Ca2+ metabolism that promotes Ca2+ release from intracellular stores and together with IP4 regulates Ca2+ homeostasis. In addition, IP4 is involved in the immune cell development. It has been proved that Ca2+/calmodulin (Ca2+/CaM) regulates the activity of IP3 3-K, via direct interaction between both enzymes. Although we have extensive structural knowledge of the kinase domains of the three IP3 3-K isoforms, no structural information is available about the interaction between IP3 3-K and Ca2+/CaM. Here we describe the crystal structure of the complex between human Ca2+/CaM and the CaM binding region of human IP3 3-K isoform A (residues 158 to 183), and propose a model for a complex including the kinase domain. The structure obtained allowed us to identify all the key residues involved in the interaction, which have been evaluated by site directed mutagenesis, pull-down and fluorescence anisotropy experiments. The results allowed the identification of a new CaM binding motif expanding our knowledge about how CaM interacts with its partners.
A new calmodulin binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation.,Franco-Echevarria E, Banos-Sanz JI, Monterroso B, Round A, Sanz-Aparicio J, Gonzalez B Biochem J. 2014 Aug 7. PMID:25101901[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
- ↑ Franco-Echevarria E, Banos-Sanz JI, Monterroso B, Round A, Sanz-Aparicio J, Gonzalez B. A new calmodulin binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation. Biochem J. 2014 Aug 7. PMID:25101901 doi:http://dx.doi.org/10.1042/BJ20140757
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