ID:NFIP1_HUMAN DESCRIPTION: RecName: Full=NEDD4 family-interacting protein 1; AltName: Full=Breast cancer-associated protein SGA-1M; AltName: Full=NEDD4 WW domain-binding protein 5; AltName: Full=Putative MAPK-activating protein PM13; AltName: Full=Putative NF-kappa-B-activating protein 164; AltName: Full=Putative NFKB and MAPK-activating protein; FUNCTION: Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cells-mediated inflammation by activating ITCH and thus controlling JUNB degradation (By similarity). In cortical neurons, mediates the ubiquitination of SLC11A2/DMT1 by NEDD4L, leading to down-regulation of the divalent metal transporter and protection of the cells from cobalt and 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 and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate. SUBUNIT: Forms heterodimers with NDFIP2. Interacts with several E3 ubiquitin-protein ligases, including NEDD4, NEDD4L and WWP2. Interacts with ITCH, U2SURP and WWP2 (By similarity). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion. Interacts with SLC11A2/DMT1. Interacts with PTEN. May interact with phosphorylated EGFR. SUBCELLULAR LOCATION: Endosome membrane; Multi-pass membrane protein. Golgi apparatus membrane (By similarity). Secreted. Note=Detected in exosomes and secreted via the exosomal pathway. TISSUE SPECIFICITY: Widely expressed. Higher levels are detected in cerebellum, pituitary, thalamus, kidney, liver, testis, salivary glands and placenta. Also expressed in fetal brain, kidney and lung. INDUCTION: Increased protein expression in neuronal cells in response to Co(2+) or Fe(2+) ions. DOMAIN: The PY (WW-binding) motifs are required for E3 ubiquitin- protein ligase binding and activation and for ubiquitination. PTM: Ubiquitinated by NEDD4 and ITCH; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation. PTM: Undergoes transient tyrosine phosphorylation following EGF stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF10176 - Protein of unknown function (DUF2370)
ModBase Predicted Comparative 3D Structure on Q9BT67
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002761 regulation of myeloid leukocyte differentiation GO:0002829 negative regulation of type 2 immune response GO:0006879 cellular iron ion homeostasis GO:0007034 vacuolar transport GO:0010629 negative regulation of gene expression GO:0030001 metal ion transport GO:0031398 positive regulation of protein ubiquitination GO:0032410 negative regulation of transporter activity GO:0032713 negative regulation of interleukin-4 production GO:0042130 negative regulation of T cell proliferation GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0045619 regulation of lymphocyte differentiation GO:0045732 positive regulation of protein catabolic process GO:0048294 negative regulation of isotype switching to IgE isotypes GO:0048302 regulation of isotype switching to IgG isotypes GO:0050728 negative regulation of inflammatory response GO:0051224 negative regulation of protein transport
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
