Septins are a family of conserved proteins that are essential for cytokinesis in 
a wide range of organisms including fungi, Drosophila and mammals. In budding 
yeast, where they were first discovered, they are thought to form a filamentous 
ring at the bridge between the mother and bud cells. What regulates the assembly 
and function of septins, however, has remained obscure. All septins share a 
highly conserved domain related to those found in small GTPases, and septins 
have been shown to bind and hydrolyze GTP, although the properties of this 
domain and the relationship between polymerization and GTP binding/hydrolysis is 
unclear. Here we show that human septin 2 is phosphorylated in vivo at Ser218 by 
casein kinase II. In addition, we show that recombinant septin 2 binds guanine 
nucleotides with a Kd of 0.28 microm for GTPgammaS and 1.75 microm for GDP. It 
has a slow exchange rate of 7 x 10(-5) s(-1) for GTPgammaS and 5 x 10(-4) s(-1) 
for GDP, and an apparent kcat value of 2.7 x 10(-4) s(-1), similar to those of 
the Ras superfamily of GTPases. Interestingly, the nucleotide binding affinity 
appears to be altered by phosphorylation at Ser218. Finally, we show that a 
single septin protein can form homotypic filaments in vitro, whether bound to 
GDP or GTP.