Calcineurin acts on a select group of protein substrates by recognizing two SLiMs, PxIxIT and LxVP, which occur in disordered, accessible, protein regions, but may be hundreds of residues away from sites of dephophosphorylation and are found at variable distances and orientations with respect to each other. PxIxIT and LxVP sequences were first defined in the NFAT (nuclear factor of activated T-cells) family of transcription factors, whose nuclear accumulation is triggered by calcineurin-mediated dephosphorylation to initiate gene expression and promote T-cell activation. Subsequently, PxIxIT and LxVP motifs were identified in multiple calcineurin substrates from humans and budding yeast (S. cerevisiae), and their binding surfaces on calcineurin shown to be broadly conserved, suggesting that this characteristic mode of substrate recognition is retained throughout the fungal and animal kingdoms.
Filter: PxIxIT & LxVP | PxIxIT | LxVP | Predicted
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