Knotted polymers have been found in biological systems, such as DNA knotting in phage capsids. Many biochemical reactions involve a close spatial contact between two reactive sites of a biopolymer and are often limited by the diffusive encounter rate of reacting groups. Therefore, the intrachain reaction is significantly regulated by topological constraints due to knotting. We investigated the reversible intrachain reaction of a knotted flexible polymer by Monte Carlo simulation and demonstrated that the intraknot association-dissociation crossover is mainly governed by both the essential crossing number and the topological similarity. Depending on the contour separation between reactive sites, the reaction may display qualitatively different behavior. The knotting (increment of the crossing number) favors the reaction with global contour separation but hinders that with local contour separation. In contrast to the latter case, the topological interactions of the former are clearly classified into different homologous groups, called Conway families. This result reveals that the biopolymer may utilize the relative contour separation of reactive sites and the knotting to control the intrachain reaction.