FunctionBinds the telomeric double-stranded TTAGGG repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.
Tissue specificityHighly expressed and ubiquitous. Isoform Pin2 predominates.
DomainThe acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules. The TRFH dimerization region mediates the interaction with TINF2.
Post-translational modificationsPhosphorylated preferentially on Ser-219 in an ATM-dependent manner in response to ionizing DNA damage. ADP-ribosylation by TNKS1 or TNKS2 diminishes its ability to bind to telomeric DNA. Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.
Cellular localizationNucleus. Cytoplasm > cytoskeleton > spindle. Chromosome > telomere. Colocalizes with telomeric DNA in interphase and metaphase cells and is located at chromosome ends during metaphase. Associates with the mitotic spindle.