The mammalian tumor necrosis factor receptor (TNFR) family consists of 10 cell-surface proteins that regulate development and homeostasis of the immune system. Member 14 of TNFR (TNFRSF14, also named as TR2, ATAR, HVEA, HVEM, LIGHTR) was also identified as a mediator of herpesvirus entry into mammalian cells. The cytoplasmic region of TNFRSF14 bound to several members of the TNFR-associated factor (TRAF) family, namely TRAF1, TRAF2, TRAF3, and TRAF5. Transient transfection into human 293 cells caused marked activation of nuclear factor- B (NF- B), a transcriptional regulator of multiple immunomodulatory and inflammatory genes.