The human Cyclin E2 gene encodes a 404 amino acid protein that is most closely related to Cyclin E. Cyclin E2 mRNA levels peaks at the G1 / S transition. Cyclin E2 associates with Cdk2 in a functional kinase complex that is inhibited by both p27 (Kip1) and p21 (Cip1). Cyclin E2 / Cdk2 phosphorylates histone H1 in vitro. G1 cyclin E controls the initiation of DNA synthesis by activating CDK2. Abnormally high levels of cyclin E expression have frequently been observed in human cancers. Unlike Cyclin E1, which is expressed in great majority of proliferating normal and neoplastically transformed cells, Cyclin E2 levels are low to undetectable in non transformed cells and increase significantly in neoplasm derived cells.