Schematic kinetic diagram of motif 5 and model simulations. (a) Dashed line indicates a positive feedback loop from pE3-Ub to the phosphorylation of E3. (b) Reaction schemes depicting intra- and inter-molecular self-activation mechanisms. (c-e) Steady-state bistable responses of relevant species against gradual increasing of the kinase abundance level. The vertical arrows (blue) indicate the jump between the low and high branch of the hysteresis curves, the dashed lines indicates unstable state. (f) Comparison of bistable behaviour under four scenarios when none, only self-ubiquitination, only positive feedback loop, or both mechanisms are operating. Parameters used are given in the SI.