NGEF
Domain
The DH domain and the PH domain are both required to mediate interaction with EPHA4.
Function
Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role in axon guidance regulating ephrin-induced growth cone collapse and dendritic spine morphogenesis. Upon activation by ephrin through EPHA4, the GEF activity switches toward RHOA resulting in its activation. Activated RHOA promotes cone retraction at the expense of RAC1- and CDC42-stimulated growth cone extension (By similarity).
Post-translational modifications
Src-dependent phosphorylation at Tyr-179 upon EPHA4 activation increases the guanine exchange factor activity toward RHOA. Phosphorylation by CDK5 upon EPHA4 activation by EFNA1 may regulate dendritic spine morphogenesis (By similarity).
Tissue Specificity
Highly expressed in brain specifically in caudate nucleus and to a lower extent in amygdala and hippocampus. Also detected in lung.
Cellular localization
- Cytoplasm
- Membrane
- Cell projection
- Growth cone
- Associated with membranes. Localizes to axonal growth cones (By similarity).
Alternative names
Ephexin-1, Eph-interacting exchange protein, Neuronal guanine nucleotide exchange factor, NGEF