NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual domain structure and a restricted expression pattern

Neuroscience. 2002;112(1):51-63. doi: 10.1016/s0306-4522(02)00063-5.


Ca(2+)-signalling plays a major role in regulating all aspects of neuronal function. Different types of neurons exhibit characteristic differences in the responses to Ca(2+)-signals. Correlating with differences in Ca(2+)-response are expression patterns of Ca(2+)-binding proteins that often serve as markers for various types of neurons. For example, in the cerebral cortex the EF-hand Ca(2+)-binding proteins parvalbumin and calbindin are primarily expressed in inhibitory interneurons where they influence Ca(2+)-dependent responses. We have now identified a new family of proteins called NECABs (neuronal Ca(2+)-binding proteins). NECABs contain an N-terminal EF-hand domain that binds Ca(2+), but different from many other neuronal EF-hand Ca(2+)-binding proteins, only a single EF-hand domain is present. At the C-terminus, NECABs include a DUF176 motif, a bacterial domain of unknown function that was previously not observed in eukaryotes. In rat at least three closely related NECAB genes are expressed either primarily in brain (NECABs 1 and 2) or in brain and muscle (NECAB 3). Immunocytochemistry revealed that NECAB 1 is restricted to subsets of neurons. In cerebral cortex, NECAB 1 is highly and uniformly expressed only in layer 4 pyramidal neurons, whereas in hippocampus only inhibitory interneurons and CA2 pyramidal cells contain NECAB 1. In these neurons, NECAB 1 fills the entire cytoplasm similar to other EF-hand Ca(2+)-binding proteins, and is not concentrated in any particular subcellular compartment. We suggest that NECABs represent a novel family of regulatory Ca(2+)-binding proteins with an unusual domain structure and a limited expression in a subclass of neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Brain / metabolism
  • COS Cells
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / isolation & purification
  • Calcium-Binding Proteins / metabolism*
  • Cloning, Molecular
  • Eye Proteins / genetics*
  • Eye Proteins / isolation & purification
  • Eye Proteins / metabolism*
  • Immunohistochemistry
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Protein Isoforms / isolation & purification
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tissue Distribution


  • Calcium-Binding Proteins
  • Eye Proteins
  • NECAB2 protein, mouse
  • Protein Isoforms
  • RNA, Messenger