FASLG
This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described
Alternative Names
Fas Ligand
Research Area
Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058).
Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:9228058, PubMed:7528780, PubMed:9427603).
Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity).
TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity).
Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (PubMed:27806260).
Tumor necrosis factor ligand superfamily member 6, soluble form:
Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways (By similarity).
Can induce apoptosis but does not appear to be essential for this process (PubMed:27806260).
FasL intracellular domain:
Cytoplasmic form induces gene transcription inhibition.
Biological Process
Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
Apoptotic process Source: ProtInc
Apoptotic signaling pathway Source: BHF-UCL
Cell-cell signaling Source: ProtInc
Cellular chloride ion homeostasis Source: Ensembl
Cellular response to interferon-gamma Source: Ensembl
Endosomal lumen acidification Source: Ensembl
Extrinsic apoptotic signaling pathway Source: UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
Inflammatory cell apoptotic process Source: Ensembl
Necroptotic process Source: BHF-UCL
Necroptotic signaling pathway Source: BHF-UCL
Negative regulation of angiogenesis Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of cell population proliferation Source: Ensembl
Positive regulation of endothelial cell apoptotic process Source: BHF-UCL
Positive regulation of epidermal growth factor receptor signaling pathway Source: Ensembl
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of neuron apoptotic process Source: Ensembl
Positive regulation of phosphatidylserine exposure on apoptotic cell surface Source: UniProtKB
Release of sequestered calcium ion into cytosol by endoplasmic reticulum Source: MGI
Response to growth factor Source: Ensembl
Response to lipopolysaccharide Source: Ensembl
Retinal cell programmed cell death Source: Ensembl
Signal transduction Source: ProtInc
T cell apoptotic process Source: UniProtKB
Cellular Location
Lysosome lumen; Cell membrane; Cytoplasmic vesicle lumen. Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination (PubMed:17164290). Colocalizes with the SPPL2A protease at the cell membrane (PubMed:17557115).
Tumor necrosis factor ligand superfamily member 6, soluble form: Secreted. May be released into the extracellular fluid by cleavage from the cell surface.
FasL intracellular domain: Nucleus. The FasL ICD cytoplasmic form is translocated into the nucleus.
Involvement in disease
Autoimmune lymphoproliferative syndrome 1B (ALPS1B):
A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.
Topology
Cytoplasmic: 1-80
Helical: 81-102
Extracellular: 103-281
PTM
The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form undergoes two successive intramembrane proteolytic cleavages. The first one is processed by ADAM10 producing an N-terminal fragment, which lacks the receptor-binding extracellular domain. This ADAM10-processed FasL (FasL APL) remnant form is still membrane anchored and further processed by SPPL2A that liberates the FasL intracellular domain (FasL ICD). FasL shedding by ADAM10 is a prerequisite for subsequent intramembrane cleavage by SPPL2A in T-cells.
N-glycosylated (PubMed:9228058). Glycosylation enhances apoptotic activity (PubMed:27806260).
Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization.
Monoubiquitinated.
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Datasheet