FAS Ligand, Soluble (FAS LIGAND) Human Active Protein

The protein encoded by this gene is the ligand for FAS. Both are transmembrane proteins. Interaction of FAS with this ligand is critical in triggering apoptosis of some types of cells such as lymphocytes. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). [provided by RefSeq, Jul 2008]

Function: Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. May be involved in cytotoxic T-cell mediated apoptosis and in T-cell development. TNFRSF6/FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. Binding to the decoy receptor TNFRSF6B/DcR3 modulates its effects. Ref.12The FasL intracellular domain (FasL ICD) cytoplasmic form induces gene transcription inhibition. Ref.12

Subunit structure: Homotrimer

Probable. Interacts with ARHGAP9, BAIAP2L1, BTK, CACNB3, CACNB4, CRK, DLG2, DNMBP, DOCK4, EPS8L3, FGR, FYB, FYN, HCK, ITK, ITSN2, KALRN, LYN, MACC1, MIA, MPP4, MYO15A, NCF1, NCK1, NCK2, NCKIPSD, OSTF1, PIK3R1, PSTPIP1, RIMBP3C, SAMSN1, SH3GL3, SH3PXD2B, SH3PXD2A, SH3RF2, SKAP2, SNX33, SNX9, SORBS3, SPTA1, SRC, SRGAP1, SRGAP2, SRGAP3, TEC, TJP3 and YES1. Ref.13 Ref.14

Subcellular location: Cell membrane; Single-pass type II membrane protein. Cytoplasmic vesicle lumen. Lysosome lumen. Note: Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination. Colocalizes with the SPPL2A protease at the cell membrane. Ref.12 Ref.13Tumor necrosis factor ligand superfamily member 6, soluble form: Secreted

By similarity. Note: May be released into the extracellular fluid, probably by cleavage form the cell surface

By similarity. Ref.12 Ref.13FasL intracellular domain: Nucleus. Note: The FasL ICD cytoplasmic form is translocated into the nucleus. Ref.12 Ref.13

Post-translational modification: 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.Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization. Ref.13Monoubiquitinated.

Involvement in disease: Autoimmune lymphoproliferative syndrome 1B (ALPS1B) [MIM:601859]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities: Belongs to the tumor necrosis factor family.