NDFIP1
Description
The NDFIP1 (Nedd4 family interacting protein 1) is a protein-coding gene located on chromosome 5.
Nedd4 family interacting protein 1 is a protein that in humans is encoded by the NDFIP1 gene.
== Function == The protein encoded by this gene belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. It is a potential target for ubiquitination by the Nedd4 family of proteins. This protein is thought to be part of a family of integral Golgi membrane proteins. [provided by RefSeq, Jul 2008].
NDFIP1 activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, which regulates the stability of their targets. This results in the control of various cellular processes. NDFIP1 prevents chronic T-helper cell-mediated inflammation by activating ITCH and controlling JUNB degradation. It promotes pancreatic beta cell death through JUNB degradation and inhibition of the unfolded protein response, leading to reduced insulin secretion. NDFIP1 also restricts pro-inflammatory cytokine production in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC. In collaboration with NDFIP2, it limits cytokine signaling and effector Th2 T-cell expansion by promoting JAK1 degradation through ITCH- and NEDD4L-mediated ubiquitination. NDFIP1 regulates peripheral T-cell tolerance to self and foreign antigens, forcing naive CD4+ T-cells out of the cell cycle before they become effector T-cells. It negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and degradation of MAVS. NDFIP1 also 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, where it mediates KCNH2 degradation. In cortical neurons, NDFIP1 mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protecting the cells from cobalt and iron toxicity. NDFIP1 is crucial for normal dendrite and dendritic spine development in the cortex. It enhances the ubiquitination of BRAT1 by NEDD4, NEDD4L, and ITCH, and is required for the nuclear localization of ubiquitinated BRAT1. NDFIP1 enhances ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH. NDFIP1 modulates EGFR signaling through multiple pathways. It may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 possibly through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. This may control cell growth rate. NDFIP1 inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity. It forms heterodimers with NDFIP2. NDFIP1 interacts with various E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, and WWP2. The interaction with NEDD4, NEDD4L, and ITCH leads to their relocalization to exosomes and eventually to exosomal secretion. NDFIP1 interacts with U2SURP, SLC11A2/DMT1, PTEN, and may interact with phosphorylated EGFR. It interacts with BRAT1, KCNH2, and MAVS. NDFIP1 is part of a complex containing ITCH, NDFIP1, and MAP3K7. It interacts (via N-terminus) with UBE2L3, and this interaction mediates the recruitment of UBE2L3 to ITCH.
NDFIP1 is also known as N4WBP5.
