Alternative titles; symbolsDECOY RECEPTOR 3; DCR3TR6HGNC Approved Gene Symbol: TNFRSF6BCytogenetic location: 20q13.33 Genomic coordinates (GRCh38): 20:63,696...
Alternative titles; symbols
HGNC Approved Gene Symbol: TNFRSF6B
Cytogenetic location: 20q13.33 Genomic coordinates (GRCh38): 20:63,696,651-63,698,683 (from NCBI)
▼ Cloning and Expression
Pitti et al. (1998) identified ESTs that showed homology to the tumor necrosis factor receptor (TNFR; see 191190) superfamily. Using PCR with primers based on the region of EST consensus, they isolated a cDNA encoding TNFRSF6B, which termed decoy receptor-3 (DCR3), from a human fetal lung cDNA library. The DCR3 protein contains 300 amino acids and has a molecular mass of 35 kD. By Northern blot analysis, Pitti et al. (1998) detected a 1.2-kb transcript in human fetal lung, brain, and liver, and in adult spleen, colon, and lung. Like osteoprotegerin (OPG; 602643), another TNFR superfamily member, DCR3 lacks an apparent transmembrane sequence, indicating that DCR3 may be a secreted, rather than a membrane-associated, molecule. The DCR3 protein shares 31% sequence homology with OPG, and all of the cysteines in the 4 cysteine-rich domains of DCR3 and OPG are conserved. Pitti et al. (1998) stated that DCR3 and OPG define a subset of TNFR family members that function as secreted decoys to modulate ligands that induce apoptosis.
Bai et al. (2000) independently identified the TNFRSF6B gene, which they called M68. M68 genomic DNA, mRNA, and protein levels were examined in a series of human gastrointestinal tract tumors. Using M68 immunohistochemistry and a scoring system similar to that used for HER-2/neu (ERBB2; 164870), they found that M68 protein was overexpressed in 30 of 68 (44%) human adenocarcinomas of the esophagus, stomach, colon, and rectum. Tumors examined by Northern blot revealed M68 mRNA highly elevated in a similar fraction of primary tumors from the same gastrointestinal tract regions, as well as in 2 colon adenocarcinoma cell lines. They also found M68 protein to be overexpressed in a substantial number of tumors in which gene amplification could not be detected by fluorescence in situ hybridization or quantitative genomic PCR, suggesting that overexpression of M68 may precede amplification in tumors. Bai et al. (2000) showed that M68 lies within a 4-gene cluster that includes a novel helicase-like gene (NHL; 608833) related to RAD3/ERCC2 (126340), a plasma membrane Ras-related GTPase and a member of the stathmin family (151442), amplification or overexpression of which may also contribute to cell growth and tumor progression.
By radiation hybrid analysis and by linkage to a mapped marker, Pitti et al. (1998) assigned the TNFRSF6B gene to chromosome 20q13.
▼ Gene Function
Fas ligand (FASL; 134638) is produced by activated T cells and natural killer cells, and it induces apoptosis (programmed cell death) in target cells through the death receptor FAS (134637). An important role of FASL and FAS is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumor cells. Pitti et al. (1998) demonstrated that DCR3 binds to FASL and inhibits FASL-induced apoptosis. They also found that the DCR3 gene was amplified in about half of 35 primary lung and colon tumors studied and that DCR3 mRNA was expressed in malignant tissue. Thus, certain tumors may escape FASL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FASL.