TNFRSF14
This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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 (PubMed:9462508, PubMed:10754304, PubMed:18193050, PubMed:23761635).
Signals via the TRAF2-TRAF3 E3 ligase pathway to promote immune cell survival and differentiation (PubMed:19915044, PubMed:9153189, PubMed:9162022).
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 (PubMed:10754304).
Interacts with CD160 on NK cells, enhancing IFNG production and anti-tumor immune response (PubMed:23761635).
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 (By similarity).
Upon binding to CD160 on activated CD4+ T cells, down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050).
May interact in cis (on the same cell) or in trans (on other cells) with BTLA (PubMed:19915044) (By similarity).
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:19915044) (By similarity).
(Microbial infection) Acts as a receptor for Herpes simplex virus 1/HHV-1.
(Microbial infection) Acts as a receptor for Herpes simplex virus 2/HHV-2.
Biological Process
Biological Process adaptive immune response Source:UniProtKB-KW
Biological Process cell surface receptor signaling pathway Source:ProtInc1 Publication
Biological Process defense response to Gram-negative bacterium Source:GO_Central1 Publication
Biological Process defense response to Gram-positive bacterium Source:GO_Central1 Publication
Biological Process immune response Source:ProtInc1 Publication
Biological Process innate immune response Source:UniProtKB-KW
Biological Process negative regulation of adaptive immune memory response Source:UniProtKB1 Publication
Biological Process negative regulation of alpha-beta T cell proliferation Source:GO_Central1 Publication
Biological Process positive regulation of cytokine production involved in immune response Source:GO_Central1 Publication
Biological Process positive regulation of peptidyl-tyrosine phosphorylation Source:GO_Central1 Publication
Biological Process positive regulation of T cell migration Source:GO_Central1 Publication
Biological Process T cell costimulation Source:UniProtKB1 Publication
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Datasheet