TRAF3IP3

TRAF3IP3 is a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. TRAF3IP3 may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit.

Full Name

TRAF3 interacting protein 3

Function

Adapter protein that plays essential roles in both innate and adaptive immunity. Plays a crucial role in the regulation of thymocyte development (PubMed:26195727).
Mechanistically, mediates TCR-stimulated activation through recruiting MAP2K1/MEK1 to the Golgi and, thereby, facilitating the interaction of MAP2K1/MEK1 with its activator BRAF (PubMed:26195727).
Also plays an essential role in regulatory T-cell stability and function by recruiting the serine-threonine phosphatase catalytic subunit (PPP2CA) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component RPTOR and restricting glycolytic metabolism (PubMed:30115741).
Positively regulates TLR4 signaling activity in macrophage-mediated inflammation by acting as a molecular clamp to facilitate LPS-induced translocation of TLR4 to lipid rafts (PubMed:30573680).
In response to viral infection, facilitates the recruitment of TRAF3 to MAVS within mitochondria leading to IRF3 activation and interferon production (PubMed:31390091).
However, participates in the maintenance of immune homeostasis and the prevention of overzealous innate immunity by promoting 'Lys-48'-dependent ubiquitination of TBK1 (PubMed:32366851).

Cellular Location

Cell membrane
Golgi apparatus membrane
Lysosome membrane
Mitochondrion outer membrane
Accumulates on the mitochondria after virus infection.

Topology

Cytoplasmic: 1-526
Helical: 527-544
Extracellular: 545-551