An Update to Calcium Binding Proteins

  • Jacobo Elíes
  • Matilde Yáñez
  • Thiago M. C. Pereira
  • José Gil-Longo
  • David A. MacDougall
  • Manuel Campos-ToimilEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1131)


Ca2+ binding proteins (CBP) are of key importance for calcium to play its role as a pivotal second messenger. CBP bind Ca2+ in specific domains, contributing to the regulation of its concentration at the cytosol and intracellular stores. They also participate in numerous cellular functions by acting as Ca2+ transporters across cell membranes or as Ca2+-modulated sensors, i.e. decoding Ca2+ signals. Since CBP are integral to normal physiological processes, possible roles for them in a variety of diseases has attracted growing interest in recent years. In addition, research on CBP has been reinforced with advances in the structural characterization of new CBP family members. In this chapter we have updated a previous review on CBP, covering in more depth potential participation in physiopathological processes and candidacy for pharmacological targets in many diseases. We review intracellular CBP that contain the structural EF-hand domain: parvalbumin, calmodulin, S100 proteins, calcineurin and neuronal Ca2+ sensor proteins (NCS). We also address intracellular CBP lacking the EF-hand domain: annexins, CBP within intracellular Ca2+ stores (paying special attention to calreticulin and calsequestrin), proteins that contain a C2 domain (such as protein kinase C (PKC) or synaptotagmin) and other proteins of interest, such as regucalcin or proprotein convertase subtisilin kexins (PCSK). Finally, we summarise the latest findings on extracellular CBP, classified according to their Ca2+ binding structures: (i) EF-hand domains; (ii) EGF-like domains; (iii) ɣ-carboxyl glutamic acid (GLA)-rich domains; (iv) cadherin domains; (v) Ca2+-dependent (C)-type lectin-like domains; (vi) Ca2+-binding pockets of family C G-protein-coupled receptors.


Annexins Ca2+ sensors Calcineurin Calmodulin Calreticulin EF-hand domain Parvalbumin Protein kinase C S100 proteins Synaptotagmin 


Author Contribution

JE was responsible for the writing of Sect. 8.2; he also participated in the drafting of the Introduction and Concluding Remarks sections. MY was responsible for the writing of Sect. 8.2. TMCP and JGL were responsible for the writing of Sect. 8.4. DAM contributed throughout, provided focus and flow to the various sections of the review, and oversaw/edited written English. MCT was responsible for the writing of Sect. 8.3; he also participated in the writing of the Introduction and Concluding Remarks sections and in the coordination of all authors.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Pharmacology and Experimental Therapeutics, Faculty of Life SciencesUniversity of BradfordBradfordUK
  2. 2.Pharmacology of Chronic Diseases (CD Pharma), Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS)Universidad de Santiago de CompostelaSantiago de CompostelaSpain
  3. 3.Pharmaceutical Sciences Graduate ProgramVila Velha University (UVV)Vila VelhaBrazil
  4. 4.Federal Institute of Education, Science and Technology (IFES)Vila VelhaBrazil
  5. 5.Research and EnterpriseUniversity of HuddersfieldHuddersfieldUK

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