NEDD4 family-interacting protein 1; breast cancer-associated protein SGA-1M; NEDD4 WW domain-binding protein 5; MAPK-activating protein PM13; NF-kappa-B-activating protein 164; NFKB & MAPK-activating protein (NDFIP1 N4WBP5 PSEC0192 PSEC0223)

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Function

activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 & ITCH, & consequently modulates the stability of their targets.
prevents chronic T-helper cells-mediated inflammation by activating ITCH & thus controlling JUNB degradation
in cortical neurons, mediates ubiquitination of SLC11A2/DMT1 by NEDD4L, leading to down-regulation of the divalent metal transporter & protection of the cells from cobalt & iron toxicity
modulates EGFR signaling through multiple pathways
- in particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization & on MAPK8 through ITCH- dependent MAP2K4 inactivation
ubiquitinated by NEDD4 & ITCH; mono-, di- & polyubiquitinated forms are detected
ubiquitination regulates its degradation
undergoes transient Tyr phosphorylation following EGF stimulation, most probably by catalyzed by SRC
phosphorylation by SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1
forms heterodimers with NDFIP2
interacts with several E3 ubiquitin-protein ligases, including NEDD4, NEDD4L & WWP2
interacts with ITCH, U2SURP & WWP2 (putative)
interaction with NEDD4, NEDD4L & ITCH leads to relocalization of these proteins to exosomes & eventually to exosomal secretion
interacts with SLC11A2/DMT1
interacts with PTEN
may interact with phosphorylated EGFR

the PY (WW-binding) motifs are required for E3 ubiquitin- protein ligase binding & activation & for ubiquitination
WW-binding motifs mediate interaction with NEDD4

widely expressed
higher levels are detected in cerebellum, pituitary, thalamus, kidney, liver, testis, salivary glands & placenta
expressed in fetal brain, kidney, lung