NDFIP2
Domain
The PPxY motifs are required for E3 ubiquitin-protein ligase activation and for ubiquitination.
Function
Activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 and WWP2, and consequently modulates the stability of their targets. As a result, may control many cellular processes. Recruits ITCH, NEDD4 and SMURF2 to endosomal membranes. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus and multivesicular body where it mediates KCNH2 degradation (PubMed:26363003). May modulate EGFR signaling. Together with NDFIP1, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (By similarity).
Post-translational modifications
Ubiquitinated by NEDD4 and ITCH. Also ubiquitinated by NEDD4L. Ubiquitination by NEDD4 or NEDD4L does not affect turnover (By similarity).
Undergoes transient tyrosine-phosphorylation following EGF stimulation, most probably catalyzed by SRC. Phosphorylation on Tyr-151, Tyr-171 and Tyr-177 are dependent on the phosphorylation on Tyr-167. Also phosphorylated by LYN and FYN.
Tissue Specificity
Expressed in brain, lung, heart, skeletal muscle, kidney, liver and placenta.
Cellular localization
- Endosome membrane
- Multi-pass membrane protein
- Golgi apparatus membrane
- Endosome
- Multivesicular body membrane
Alternative names
KIAA1165, N4WBP5A, NDFIP2, NEDD4 family-interacting protein 2, NEDD4 WW domain-binding protein 5A, Putative MAPK-activating protein PM04/PM05/PM06/PM07, Putative NF-kappa-B-activating protein 413