Encyclopedia of Metalloproteins

2013 Edition
| Editors: Robert H. Kretsinger, Vladimir N. Uversky, Eugene A. Permyakov

Calbindin D28k

  • Karin Åkerfeldt
  • Tommy Cedervall
  • Mikael Bauer
  • Sara Linse
Reference work entry
DOI: https://doi.org/10.1007/978-1-4614-1533-6_37



EF-hand: helix-loop-helix motif obeying a 29-residue consensus sequence with hydrophobic and Ca2+-ligating residues in defined positions, typically forming a pentagonal bipyramidal coordination sphere.

Hexa EF-hand (HEF) proteins: Ca2+-binding proteins containing six EF-hand motifs.

Domain: Independent folding unit.

Subdomain: Super-secondary motif which is part of a domain.

Deamidation: Spontaneous hydrolysis of a carboxamide to a carboxylic acid via a cyclic intermediate. Deamidation of asparagine typically leads to iso-aspartate and aspartate in a 2:1 molar ratio.

Chromophoric chelator: Metal-binding dye which changes its optical spectrum upon chelation.

Discovery and Prevalence

Calbindin D28k was originally purified from chicken intestine (Wasserman and Taylor 1996)...

This is a preview of subscription content, log in to check access.


  1. Åkerfeldt KS, Coyne AN, Wilk RR et al (1996) Ca2+-binding stoichiometry of calbindin D28k as assessed by spectroscopic analyses of synthetic peptide fragments. Biochemistry 35:3662–3669CrossRefPubMedGoogle Scholar
  2. André I, Linse S (2002) Measurement of Ca2+-binding constants of proteins and presentation of the CaLigator software. Anal Biochem 305:195–205CrossRefPubMedGoogle Scholar
  3. Bauer MC, Frohm B, Malm J et al (2008) S. Zn2+ binding to human calbindin D28k. Protein Sci 17:760–767CrossRefPubMedGoogle Scholar
  4. Bellido T, Huening M, Raval-Pandya M et al (2000) Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase-3 activity. J Biol Chem 275:26328–26332CrossRefPubMedGoogle Scholar
  5. Berggård T, Thulin E, Åkerfeldt KS et al (2000a) Fragment complementation of human calbindin D28k. Protein Sci 9:2094–2108CrossRefPubMedGoogle Scholar
  6. Berggård T, Silow M, Thulin E et al (2000b) Ca2+ and H+ dependent conformational changes of calbindin D28k. Biochemistry 39:6864–6873CrossRefPubMedGoogle Scholar
  7. Berggård T, Miron S, Önnerfjord P et al (2002a) Calbindin D28k exhibits properties characteristic of a Ca2+ sensor. J Biol Chem 277:16662–16672CrossRefPubMedGoogle Scholar
  8. Berggård T, Szczepankiewicz O, Thulin E et al (2002b) myo-inositol monophosphatase is an activated target of calbindin D28k. J Biol Chem 277:41954–41959CrossRefPubMedGoogle Scholar
  9. Cedervall T, Berggård T, Borek V et al (2005a) Redox sensitive cysteine residues in Calbindin D28k are structurally and functionally important. Biochemistry 44:684–693CrossRefPubMedGoogle Scholar
  10. Cedervall T, André I, Selah C et al (2005b) Calbindin D28k EF-hand ligand binding and oligomerization – four high affinity sites, three modes of action. Biochemistry 44:13522–13532CrossRefPubMedGoogle Scholar
  11. Helgstrand M, Vanbelle C, Thulin E, Linse S, Akke M (2004) Sequential 1H, 15N and 13C NMR assignment of human calbindin D28k. J Biomol NMR 28:305–306CrossRefPubMedGoogle Scholar
  12. Hobbs CA, Deterding LJ, Perera L et al (2009) Structural characterization of the conformational change in calbindin-D28k upon calcium binding using differential surface modification analyzed by mass spectrometry. Biochemistry 48:8603–8614CrossRefPubMedGoogle Scholar
  13. Kojetin DJ, Venters RA, Kordys DR et al (2006) Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D28K. Nat Struct Mol Biol 13:641–647CrossRefPubMedGoogle Scholar
  14. Kordys DR, Bobay BG, Thompson RJ et al (2007) Peptide binding proclivities of calcium loaded calbindin-D28k. FEBS Lett 581:4778–4778CrossRefPubMedGoogle Scholar
  15. Lambers TT, Mahieu F, Oancea E et al (2006) Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport. EMBO J 25:2978–2988CrossRefPubMedGoogle Scholar
  16. Leathers VL, Linse S, Forsen S et al (1990) Calbindin-D28K, a 1 alpha, 25 dihydroxyvitamin D3-induced calcium-binding protein, binds five or six Ca2+ ions with high affinity. J Biol Chem 265:9838–9841PubMedGoogle Scholar
  17. Linse S, Thulin E, Gifford LK et al (1997) Domain organization of calbindin D28k as determined from the association of six synthetic EF-hand fragments. Protein Sci 6:2385–2396CrossRefPubMedGoogle Scholar
  18. Permyakov EA, Kretsinger RH (2011) EF-hand proteins. In: Uversky VN (ed) Calcium binding proteins, Chapter 11, Section 11.5, Proteins with Six EF-Hands. Wiley, SingaporeGoogle Scholar
  19. Schmidt H, Schwaller B, Eilers J (2005) Calbindin D28k targets myo-inositol monophosphatase in spines and dendrites of cerebellar purkinje neurons. Proc Natl Acad Sci USA 102:5850–5855CrossRefPubMedGoogle Scholar
  20. Tao L, Murphy ME, English AM (2002) S-nitrosation of Ca(2+)-loaded and Ca(2+)-free recombinant calbindin D(28K) from human brain. Biochemistry 41:6185–6192CrossRefPubMedGoogle Scholar
  21. Thulin E, Linse S (1999) Expression and purification of human calbindin D28k. Protein Expr Purif 15:271–281CrossRefGoogle Scholar
  22. Vanbelle C, Halgand F, Cedervall T et al (2005) Deamidation and disulfide bridge formation in human calbindin D28k with effects on calcium binding. Protein Sci 14:968–979CrossRefPubMedGoogle Scholar
  23. Venters RA, Benson LM, Craig TA (2003) The effects of Ca(2+) binding on the conformation of calbindin D(28K): a nuclear magnetic resonance and microelectrospray mass spectrometry study. Anal Biochem 317:59–66CrossRefPubMedGoogle Scholar
  24. Wasserman RH, Taylor AN (1996) Vitamin D3 induced calcium-binding protein in chick intestinal mucosa. Science 152:791–793CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of ChemistryHaverford CollegeHaverfordUSA
  2. 2.Department of Biochemistry and Structural BiologyLund University, Chemical CentreLundSweden