The family of signal transducers and activators of transcription (STAT) is essential in cytokine and growth factor signaling. Upon cytokine and growth factor stimulation of cells, cytoplasmic unphosphorylated STAT molecules become tyrosine phosphorylated, dimerize through reciprocal phosphotyrosine (pTyr)-SH2 interactions, accumulate in the nucleus, bind to DNA, and activate gene transcription. Subsequent inactivation involves phospho-STATs coming off DNA, becoming dephosphorylated, and exported to the cytoplasm.

Seven different STAT genes have been identified so far in mammals and the corresponding protein monomers share six structural regions: N-domain (ND), coiled-coil domain (CCD), DNA-binding domain (DBD), linker domain, SH2 domain, and transcriptional activation domain. The core fragment that characterises this proteins lack the first and last domains. Structural domains comprising this superfamily share the structure of the coiled-coil domain, designated all-alpha (INTERPRO:IPR013800). STATs form homodimeric structures which grip DNA like a pair of pliers. The C-terminal SH2 domains hold together the monomers whilst the large 4-helix-bundle domains form the handles of the pliers. The DNA is almost entirely enclosed by the protein dimer, in contact with loops from the beta-barrel and the connector domains PMID:18433722,PMID:9671298,PMID:15780933.