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)

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 Structure: - the PY (WW-binding) motifs are required for E3 ubiquitin- protein ligase binding & activation & for ubiquitination - WW-binding motifs mediate interaction with NEDD4 Compartment: - endosome membrane, Golgi membrane (putative) - detected in exosomes & secreted via the exosomal pathway Alternative splicing: named isoforms=2 Expression: - widely expressed - higher levels are detected in cerebellum, pituitary, thalamus, kidney, liver, testis, salivary glands & placenta - expressed in fetal brain, kidney, lung

Properties

SIZE: entity length = 221 aa MW = 25 kD COMPARTMENT: golgi MOTIF: cytoplasmic domain {1-116} MOTIF: PY 1 {40-42} PY 2 {65-67} PY 3 {74-76} transmembrane domain {117-137} exoplasmic loop {138-143} transmembrane domain {144-164} cytoplasmic loop {165-172} transmembrane domain {173-193} exoplasmic domain {194-221}

Database Correlations

OMIM 612050 UniProt Q9BT67 Pfam PF10176 Entrez Gene 80762 Kegg hsa:80762

References

UniProt :accession Q9BT67