Activation loop

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Kinase Glossary: Activation loop

The activation loop of an ePK kinase is a flexible loop, close to the catalytic loop. Most kinases are activated by phosphorylation of specific residues in the activation loop, which then counteract the positive charge of the arginine in the catalytic loop HRD motif. Tyrosine kinases usually have one or two tyrosines in the loop, MAPK kinases have a T[DE]Y motif, which is phosphorylated on both T and Y, and most other kinases have a threonine within the loop. The activation loop is also known as the T-loop. The region just after the activation loop is called the P+1 loop, which often binds the substrate residue just C-terminal of the phosphorylated one (the P+1 residue). Together, the activation loop and P+1 loop constitute the activation segment which runs from the DFG motif to the APE motif.


  1. Scheeff ED, Eswaran J, Bunkoczi G, Knapp S, and Manning G. Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site. Structure. 2009 Jan 14;17(1):128-38. DOI:10.1016/j.str.2008.10.018 | PubMed ID:19141289 | HubMed [Scheeff]