Faslg

Function

Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:7511063). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:19794494, PubMed:7532682). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (PubMed:19794494). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (PubMed:10779162). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (By similarity).

Tumor necrosis factor ligand superfamily member 6, soluble form

Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways (PubMed:19794494). Can induce apoptosis but does not appear to be essential for this process (By similarity).

FasL intracellular domain

Cytoplasmic form induces gene transcription inhibition.

Involvement in disease

A deficiency in this protein is the cause of generalized lymphoproliferation disease phenotype (gld). Gld mice present lymphadenopathy and autoantibody production. The phenotype is recessively inherited.

Post-translational modifications

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.

Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization.

N-glycosylated. Glycosylation enhances apoptotic activity.

Monoubiquitinated.

Sequence Similarities

Belongs to the tumor necrosis factor family.

Tissue Specificity

Expressed in T-cells (PubMed:19794494). Expressed in natural killer cells (PubMed:7532682).

Cellular localization

• Isoform FasL
• Cell membrane
• Single-pass type II membrane protein
• Cytoplasmic vesicle lumen
• Lysosome lumen
• Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination. Colocalizes with the SPPL2A protease at the cell membrane.
• 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.

Alternative names

CD178, Apt1lg1, Cd95l, Fasl, gld, Tnfsf6, Faslg, Tumor necrosis factor ligand superfamily member 6, CD95 ligand, Fas antigen ligand, CD95-L, Fas ligand, FasL

Database links

swissprot:P41047 entrezGene:14103

Other research areas

• Oncology