The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been linked to increased cancer susceptibility, particularly in hereditary nonpolyposis colorectal cancer in humans. The role of the PWWP domain in MSH6 is not clear; MSH6 orthologs found in S. cerevisiae, Caenorhabditis elegans and Arabidopsis thaliana lack the PWWP domain. Histone methyltransferases (HMTases) induce the posttranslational methylation of lysine residues in histones and play a role in apoptosis. In the HMTase Whistle, the PWWP domain is necessary for HMTase activity. The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids. The PWWP domain is found in numerous proteins that are involved in cell division, growth and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding, proteins that function as transcription factors regulating a variety of developmental processes.