TNFSF14
The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported. [provided by RefSeq]
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