Tnfrsf14
Domain
The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for interaction with CD160 and BTLA.
Function
Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a complex stimulatory and inhibitory signaling network (By similarity). Signals via the TRAF2-TRAF3 E3 ligase pathway to promote immune cell survival and differentiation (PubMed:19915044). Participates in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. In response to ligation of TNFSF14/LIGHT, delivers costimulatory signals to T cells, promoting cell proliferation and effector functions (By similarity). Interacts with CD160 on NK cells, enhancing IFNG production and anti-tumor immune response (PubMed:25711213). In the context of bacterial infection, acts as a signaling receptor on epithelial cells for CD160 from intraepithelial lymphocytes, triggering the production of antimicrobial proteins and pro-inflammatory cytokines (PubMed:22801499). Upon binding to CD160 on activated CD4+ T cells, down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (By similarity). May interact in cis (on the same cell) or in trans (on other cells) with BTLA (PubMed:15568026, PubMed:19915044). In cis interactions, appears to play an immune regulatory role inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, can predominate during adaptive immune response to provide survival signals to effector T cells (PubMed:15568026, PubMed:19915044).
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the tumor necrosis factor receptor superfamily.
Tissue Specificity
Expressed at mucosal sites including colon and pulmonary epithelial cells (PubMed:22801499). Expressed in naive T cells (PubMed:19915044).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
Alternative names
CD270, hvem, Tnfrsf14, Tumor necrosis factor receptor superfamily member 14, Herpes virus entry mediator A, Tumor necrosis factor receptor-like 2, Herpesvirus entry mediator A, HveA, TR2