Post-translational modification is a major mechanism by which protein function 
is regulated in eukaryotes. Instead of single-site action, many proteins such as 
histones, p53, RNA polymerase II, tubulin, Cdc25C and tyrosine kinases are 
modified at multiple sites by modifications like phosphorylation, acetylation, 
methylation, ubiquitination, sumoylation and citrullination. Multisite 
modification on a protein constitutes a complex regulatory program that 
resembles a dynamic 'molecular barcode' and transduces molecular information to 
and from signaling pathways. This program imparts effects through 
'loss-of-function' and 'gain-of-function' mechanisms. Among the latter, covalent 
modifications specifically recruit a diverse array of modules, including the SH2 
domain, 14-3-3, WW domain, Polo box, BRCT repeat, bromodomain, chromodomain, 
Tudor domain and motifs binding to ubiquitin and other protein modifiers. Such 
recruitments are often modulated by modifications occurred at neighboring and 
distant sites. Multisite modification thus coordinates intermolecular and 
intramolecular signaling for the qualitative and quantitative control of protein 
function in vivo.