Component of a MAP kinase pathway that functions presynaptically to regulate synaptic architecture and presynaptic differentiation (PubMed:15707898). Phosphorylates and activates mkk-4 (PubMed:15707898). Has a role in axonal regrowth following injury and synaptogenesis (PubMed:19737525, PubMed:19164707). Plays a role in modulating polymerization of neuronal microtubules (PubMed:21368137). Also promotes tubulin post-translational modifications that protect microtubules (PubMed:23000142). Plays a role in cilium length regulation, possibly by reducing rab-5 mediated endocytosis, and may also have a role in intraflagellar transport in cilia (PubMed:26657059). Plays a role in the formation of muscle connections, also called muscle arm extensions, between the body wall and the motor axons in the dorsal and ventral cord (PubMed:27123983). Has a role in synapse and axon development, and in axonal regrowth following injury. By forming heterooligomers with isoform a, acts as an inhibitor of isoform a activation. Its inhibitory function is independent of its catalytic activity. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Inactive when associated with isoform c. Dissociation from isoform c, which is dependent on the phosphorylation of the C-terminal hexapeptide, results in self-association and activation. Transient increase in Ca(2+) levels caused by axonal injury or synaptic activity triggers the dissociation of isoform a from isoform c; the dissociation may be influenced by the phosphorylation status of the C-terminal hexapeptide. Homooligomer (via leucine zipper domain and hexapeptide motif) (PubMed:23141066). Isoform a (via leucine zipper domain) forms a heterooligomer with isoform c (via leucine zipper domain) (PubMed:23141066). Isoform c does not self-associate (PubMed:23141066). Observed in the periactive zone of the presynaptic terminal which surrounds the synaptic vesicle clusters and active zones. Co-localizes with isoform c in synapses and axons; however, isoform a localization is independent on its interaction with isoform c. During axonal injury, recruited to the injured site. Co-localizes with isoform c in synapses and axons; however, localization is dependent of its interaction with isoform a. Expressed in nerve ring, nerve cord, neurons, and pharynx. The C-terminal hexapeptide motif is required for homooligomerization and for its activation. The C-terminal domain is important for localization to synapses and axons. Ubiquitinated by rpm-1. Negatively regulated by ubiquitination by fsn-1 bound rpm-1, followed by degradation. Phosphorylation at Ser-874 and/or at Ser-878 abolishes interaction with isoform c and promotes binding to isoform a kinase domain (likely in trans) resulting in isoform a self-association and activation. Overcome the lack of synaptogenesis caused by the loss of rpm-1 ubiquitin ligase activity (PubMed:17698012). Defects in axonal microtubule development (PubMed:19164707, PubMed:23000142). Double knockout with dlk-1 also suppresses the eva-1 receptor expression defect in the madd-3 single knockout (PubMed:27123983). Triple knockout with madd-3 and unc-54 results in paralysis (as in the unc-54 single knockout), and suppresses the lethality phenotype in the double madd-3 and unc-54 mutant (PubMed:27123983). Produced by alternative polyadenylation. The alternative polyadenylation site is in intron 7. In neurons, the usage of this polyadenylation site is regulated by the antagonist action of sydn-1 and ssup-72. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.