NEDD4 family-interacting protein 2; NEDD4 WW domain-binding protein 5A; MAPK-activating protein PM04/PM05/PM06/PM07; NF-kappa-B-activating protein 413 (NDFIP2 KIAA1165 N4WBP5A)
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Function
- endocytosis
- activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 & WWP2, & thus modulates stability of their targets
- recruits ITCH, NEDD4 & SMURF2 to endosomal membranes
- may modulate EGFR signaling
- ubiquitinated by NEDD4 & ITCH
- also ubiquitinated by NEDD4L
- ubiquitination by NEDD4 or NEDD4L does not affect turnover
- undergoes transient Tyr-phosphorylation following EGF stimulation, most probably catalyzed by SRC
- phosphorylated by LYN & FYN
- forms heterodimers with NDFIP1
- interacts with PTEN
- when phosphorylated at Tyr-167, interacts with SRC & LYN SH2 domain
- may thus act as a scaffold that recruits SRC to NDFIP1, enhancing NDFIP1 phosphorylation
- interacts with SLC11A2/DMT1
- may interact with phosphorylated EGFR
Structure
- the PY (WW-binding) motifs are required for E3 ubiquitin- protein ligase activation & for ubiquitination
Compartment
- Golgi membrane, endosome membrane, multivesicular body
- multi-pass membrane protein
Expression
- expressed in brain, lung, heart, skeletal muscle, kidney, liver, placenta.
- induced by T-cell activation