The TNFSF7 gene (Tumor Necrosis Factor Ligand Superfamily, member 7), located on chromosome 19p13, encodes a surface antigen expressed on activated T and B lymphocytes but not on resting cells. TNFSF7 is a 19 kDa protein comprising a 20-amino acid hydrophilic N-terminal domain without a signal sequence, an 18-amino acid hydrophobic transmembrane anchor region, and a C-terminal domain with two potential N-linked glycosylation sites. This structure classifies TNFSF7 as a type II transmembrane protein.
TNFSF7 is expressed on a subset of B, T, and NK cells, where it plays a costimulatory role in immune cell activation. It shares homology with other TNF receptor family ligands, including TNF-alpha, TNF-beta, and the CD40 ligand, with 19 to 24% amino acid sequence identity in the extracellular region.
In the context of breast cancer, TNFSF7 gene expression is epigenetically downregulated through DNA hypermethylation in its promoter region, as observed in the isogenic MCF10 model during cancer progression.