MAPK8IP3
Function
The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:12189133). May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (By similarity). Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:21775604).
Involvement in disease
Neurodevelopmental disorder with or without variable brain abnormalities
NEDBA
A disorder characterized by global developmental delay, impaired intellectual development, delayed walking, poor or absent speech, and variable brain anomalies including perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation by ROCK1 is crucial for the recruitment of JNK.
Sequence Similarities
Belongs to the JIP scaffold family.
Cellular localization
- Cytoplasm
- Golgi apparatus
- Cytoplasmic vesicle
- Cell projection
- Growth cone
- Cell projection
- Axon
- Cell projection
- Dendrite
- Cytoplasm
- Perinuclear region
- Localized in the soma and growth cones of differentiated neurites and the Golgi and vesicles of the early secretory compartment of epithelial cells. KIF5A/B/C-mediated transportation to axon tips is essential for its function in enhancing neuronal axon elongation.
Alternative names
JIP3, KIAA1066, MAPK8IP3, C-Jun-amino-terminal kinase-interacting protein 3, JIP-3, JNK-interacting protein 3, JNK MAP kinase scaffold protein 3, Mitogen-activated protein kinase 8-interacting protein 3