Originally, WEE1 was isolated as a gene responsible for the “wee” phenotype in fission yeast (Russell and Nurse 1987). WEE1 from fission yeast has been shown to autophosphorylate at serine and tyrosine residues, although the exact role of serine phosphorylation is still unknown. WEE1 from fission yeast and other species has been shown to phosphorylate cyclin-associated CDK at Tyr 15; this residue is located near the ATP-binding pocket of CDK. Another WEE1 family member, Myt1, can phosphorylate Thr 14 and Tyr 15 of CDKs. However, Myt1 preferentially phosphorylates Thr 14; thus, WEE1 is considered to be principally responsible for Tyr 15 phosphorylation.