Haspin

Haspin (GSG2) is an atypical kinase whose principal substrate is chromatin itself. During mitosis it phosphorylates histone H3 at Thr3 along chromosome arms and centromeres, and this H3T3ph mark is read by the chromosome passenger complex, positioning Aurora B at inner centromeres so that incorrect microtubule attachments can be corrected. Haspin activity is switched on by CDK1 and PLK1 phosphorylation and is anchored through binding to the cohesin-associated factor Pds5, connecting it to sister chromatid cohesion. The protein is large, with an N-terminal germline-specific region and a divergent C-terminal kinase domain. Inhibitors such as CHR-6494 and 5-iodotubercidin are used to dissect checkpoint and segregation functions.