STag is expressed early in the infectious cycle and is usually not essential for viral proliferation, though in most polyomaviruses it does improve replication efficiency.
The early region typically contains at least two genes and is transcribed as a single messenger RNA processed by alternative splicing.
[2][5][6] Polyomavirus STag proteins are usually around 170-200 residues long and consist of two distinct regions as a result of this genetic encoding.
[2][7] The C-terminal portion of the STag protein is distinct from LTag but shares an additional ~100 residues with middle tumor antigen in those viruses that express it, such as murine polyomavirus.
[3] Among polyomaviruses that infect birds - classified in the genus Gammapolyomavirus - the conserved cysteines characterizing these metal-binding regions are not present and there is no detectable sequence homology between the avian and mammalian STag C-termini.
In oncogenic polyomaviruses, the tumor antigens are responsible for the transformation activity, although the exact molecular mechanisms vary from one virus to another.
[13][7][17] STag is usually not capable of inducing these effects on its own, but increases efficiency of transformation or is sometimes a required component in addition to LTag.
[19] In vivo studies in rodent animal models suggest that MCPyV STag alone can be sufficient to drive transformation.