pHisphorylation: the emergence of histidine phosphorylation as a reversible regulatory modification

Highlights • Histidine phosphorylation (pHis) is reversible by specific kinases and phosphatases. • pHis is heat and acid labile, but stable under alkaline conditions. • Stable pHis analogs have enabled development of pHis-specific antibodies. • pHis antibodies and refined methods have identified new functions and substrates. • Enrichment of pHis phosphopeptides for proteomics is the next critical step.