PROSITE documentation PDOC00345

Synapsins signatures

Synapsins [1,2] are neuronal phosphoproteins that coat synaptic vesicles, bind to several elements of the cytoskeleton (including actin filaments), and are believed to function in the regulation of neurotransmitter release.

The synapsin family currently includes the highly related synapsin I and II. Both synapsins exists in two alternatively spliced variants: IA and IB; IIA and IIB, which only differ in their carboxy-termini. It also includes synapsin III.

Structurally synapsin IA/IB consist of a small N-terminal domain (referred to as the 'A' domain) that contains a serine residue which serves as an acceptor site for phosphorylation by both cyclic AMP-dependent protein kinase and Ca2+, calmodulin-dependent protein kinase I. The 'A' domain is followed by a linker domain ('B') of some 80 residues. The third domain ('C'), which contains 300 amino acids, is implicated in the binding to actin and to synaptic vesicles. The fourth domain 'D' is proline-rich and contains about 250 residues. Finally the C-terminal spliced domain is known as 'E' (in IA), or 'F' (in IB). The structure of synapsin IIA/IIB also consists of the 'A', 'B', and 'C' domains, the 'D' domain is replaced by smaller proline-rich region ('G'). Synapsin IIB ends with a small domain ('I'), while the larger C-terminal of synapsin IIA consist of two domains: 'H' and 'E' (homologous to the 'E' of IA). A diagram of the domains structure of the four synapsins is shown below.

 1        100       200       300       400       500       600       700
 |........|.........|.........|.........|.........|.........|.........|.
 +-+-------+------------------------------+------------------------+---+
 |A|   B   |               C              |              D         | E |  IA
 +-+-------+------------------------------+------------------------+---+

 +-+-------+------------------------------+------------------------+-+
 |A|   B   |               C              |              D         |F|    IB
 +-+-------+------------------------------+------------------------+-+

 +-+-------+------------------------------+---+-------+---+
 |A|   B   |               C              | G |   H   | E |               IIA
 +-+-------+------------------------------+---+-------+---+

 +-+-------+------------------------------+---+-+
 |A|   B   |               C              | G |I|                         IIB
 +-+-------+------------------------------+---+-+

We have selected two conserved regions as signature patterns for synapsins. The first one is a conserved octapeptide in domain 'A' which contains the phosphorylated serine residue; the second pattern is a highly conserved stretch of 11 residues located in the center of the 'C' domain.