Comparative analysis of tandem C2 domains from the mammalian synaptotagmin family

Colin Rickman, Molly Craxton, Shona Osborne, Bazbek Davletov

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Intracellular membrane traffic is governed by a conserved set of proteins, including Syts (synaptotagmins). The mammalian Syt family includes 15 isoforms. Syts are membrane proteins that possess tandem C2 domains (C2AB) implicated in calcium-dependent phospholipid binding. We performed a pair-wise amino acid sequence comparison, together with functional studies of rat Syt C2ABs, to examine common and divergent properties within the mammalian family. Sequence analysis indicates three different C2AB classes, the members of which share a high degree of sequence similarity. All the other C2ABs are highly divergent in sequence. Nearly half of the Syt family does not exhibit calcium/phospholipid binding in comparison to Syt I, the major brain isoform. Syts do, however, possess a more conserved function, namely calcium-independent binding to target SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) heterodimers. All tested isoforms, except Syt XII and Syt XIII, bound the target SNARE heterodimer comprising syntaxin 1 and SNAP-25 (25 kDa synaptosome-associated protein). Our present study suggests that many Syt isoforms can function in membrane trafficking to interact with the target SNARE heterodimer on the pathway to calcium-triggered membrane fusion.
Original languageEnglish
Pages (from-to)681-686
Number of pages6
JournalBiochemical Journal
Issue number2
Publication statusPublished - 1 Mar 2004


  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium
  • Calcium-Binding Proteins
  • Conserved Sequence
  • Membrane Glycoproteins
  • Membrane Proteins
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Rats
  • SNARE Proteins
  • Sequence Analysis, Protein
  • Synaptotagmins
  • Syntaxin 1
  • Vesicular Transport Proteins


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