PROSITE documentation PDOC52097

Ki-67 repeat profile

The Ki-67 protein found in vertebrates is a nuclear and nucleolar protein, which is tightly associated with somatic cell proliferation. The protein was named after the antibody that identified it. The Ki derives from Kiel (Germany), where the antibody was developed, with 67 being the well number from the 96-well plate. Ki-67 is implicated in major nuclear structural transitions during mitotic entry and exit. Ki-67 has roles in both interphase and mitotic cells, and its cellular distribution dramatically changes during cell cycle progression [1,2,3,4,5,6].

Although Ki-67 contains several conserved functional regions, the primary sequence conservation outside of these regions is low. Major regions of the Ki-67 protein include an N-terminal forkhead-associated (FHA) domain (see <PDOC50006>), a protein phosphatase 1 (PP1)-binding domain, a large unstructured central region comprising 16 tandem repeats (the "Ki-67 repeats") of 122 residues (in primates) which themselves contain a highly conserved 22-aa element (the "Ki-67 motif"), and a C-terminal LR (leucine/arginine-rich) chromatin-binding domain. The function of the Ki-67 repeats, which are encoded by a single huge exon, remains unclear. The Ki-67 tandem repeats contain residues phosphorylated by CDK1 during mitosis. Notably, Ki-67's mitotic localization and in vitro DNA binding affinity are affected by phosphorylation. In interphase, dephosphorylated Ki-67 forms fiber-like structures surrounding nucleoli, overlapping the perinucleolar heterochromatin. At the onset of mitosis, Ki-67 becomes hyperphosphorylated and thereby binds less avidly to DNA, and is highly mobile on the chromosome periphery until anaphase. On the mitotic chromosome surface, the highly positive electrostatic charge of Ki-67 serves as an electrostatic barrier important for prevention of hyperaggregation of chromosome arms. Dephosphorylation of Ki-67 during mitotic exit stimulates its dissociation from the perichromosomal layer (PCL), a ribonucleoprotein sheath coating the condensed chromosomes [1.2.3,4,5,6].

The profile we developed covers the entire Ki-67 repeat.