Characterization of Sp17: a ubiquitous three domain protein that binds heparin.

Sp17 is a protein that was originally thought to be expressed exclusively in the testis and whose primary function was binding to the extracellular matrix of the oocyte. Several recent reports have implicated Sp17 as having a role in cell-cell adhesion and/or cell migration in transformed, lymphocytic and haematopoietic cells, possibly through its interaction with extracellular heparan sulphate. In the present study, we report that Sp17's central domain (amino acids 61-117), spanning exon 3, is critical for heparin binding. Sp17 has two additional functional domains, an N-terminal domain similar to the dimer-interaction site in the cAMP-dependent protein kinase IIalpha regulatory subunit and a C-terminal calmodulin-binding domain. The mouse gene for Sp17 is 6.5 kb and contains four exons. Although Sp17 expression is highest in the testis, it is present in all of the mouse somatic tissues examined and is highly conserved throughout all mammalian species. Sp17's central domain, which is necessary for heparin binding, exhibits the greatest sequence divergence of all three domains. The Sp17 gene is induced in metastatic cells and during mucosal immune responses, and the protein appears to play an important role in cell migration and/or adhesion in somatic cells, as well as in male germ cells.