NDFIP2

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 Golgiapparatus 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).

Full Name

Nedd4 family interacting protein 2

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).

Biological Process

Metal ion transport Source: GO_Central
Negative regulation of gene expression Source: UniProtKB
Negative regulation of protein transport Source: UniProtKB
Negative regulation of transporter activity Source: UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of protein ubiquitination Source: UniProtKB
Ubiquitin-dependent protein catabolic process Source: GO_Central
Vacuolar transport Source: InterPro

Cellular Location

Endosome
Endosome membrane
multivesicular body membrane
Golgi apparatus
Golgi apparatus membrane

Topology

Cytoplasmic: 1-231
Helical: 232-252
Extracellular: 253-257
Helical: 258-278
Cytoplasmic: 279-287
Helical: 288-308
Extracellular: 309-336

PTM

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.